New Selected highlights at AIChE Annual Meeting 2024
Links to abstracts of presentations featuring use of Scale-up Suite and Mettler Toledo Technologies by AbbVie, Amgen, APC, Boehringer, BMS, GSK, Hovione, Lilly, MSD (Merck), Purdue, Takeda, US Army, Vertex
2024-Oct-15

New Scalable Synthesis of 6-Chloro-1H-pyrazolo[3,4-b]pyrazine via a Continuous Flow Formylation/Hydrazine Cyclization Cascade
Data-rich experimentation in combination with kinetic modelling using Dynochem were used to design a multi-step flow process for the formation of a bicyclic heterocycle.
2024-Oct-01

New Development and Execution of a Scalable Route to an Immunology ADC Drug-Linker for ABBV-154
The Dynochem solubility prediction utility is used to determine the optimum crystallization solvent composition for an ADC drug linker.
2024-Oct-01

New A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles
Dynochem kinetic modeling of ARC data allowed the design of safe operating conditions for a PFR reaction process run at high temperatures.
2024-Oct-01

New Selective Reduction of Cysteine Mutant Antibodies for Site-Specific Antibody–Drug Conjugates
A Dynochem kinetic model was used to fit the kinetic parameters of an antibody-drug conjugate conjugation, helping to understand the reaction selectivity and enable the design of an optimized process.
2024-Oct-01

New Kinetic Studies of the Partial Reduction and Conjugation Reactions in an Antibody-Drug Conjugate (ADC) Synthesis
To develop a better understanding of the ADC synthesis process that results in various drug-to-antibody ratios (DAR), kinetic studies of partial reduction and conjugation reactions were performed.
2024-Sep-30

New Going with the Flow: Implementation of a New Continuous Process for a Selective Acetal Deprotection
This paper covers the implementation of a flow process to resolve the throughput, yield, and manufacturing challenges associated with the key acetal deprotection stage.
2024-Sep-30

New Use of Impinging Jet to Improve Scalability in the Preparation of the ABBV-154 Drug-Linker
This paper discusses the key parameters examined to ensure successful scale-up of a mixing-sensitive reaction that demonstrated superior selectivity in flow compared to the batch process.
2024-Sep-30

New A Computer Vision Approach toward Verifying CFD Models of Stirred Tank Reactors
A Computer Vision Approach toward Verifying CFD Models of Stirred Tank Reactors
2024-Sep-30

Integration of a model-driven workflow into an industrial pharmaceutical facility: supporting process development of API crystallisation
Defines a streamlined workflow to develop a pharmaceutical crystallization. This workflow delivered thermodynamic and isothermal kinetic data for cooling crystallization of PD-299685 within 8 weeks. R-UNIFAC Solvent Selection Solubility Prediction.
2024-Jul-29

Let's bring your data up to standard
Outlining the opportunity to use S88 to capture and share development recipes and results of experiments, so that we can move away from transcription errors and create a digital thread that accelerates modeling and tech transfer.
2024-May-31

Process Intensification of the Continuous Synthesis of Bio-Derived Monomers for Sustainable Coatings Using a Taylor Vortex Flow Reactor
A 2-step synthesis of alkoxybutenolide monomers was optimized using a Taylor Vortex flow reactor. The kinetics of the first photo-oxidation step were modeled using Reaction Lab, and the results used to optimize the reaction.
2024-May-10

Kinetic Modeling to De-Risk Process Changes As a Part of Life-Cycle Management
During drug substance development, project teams invent, optimize, and thoroughly characterize manufacturing processes to make the drug substance in a safe, sustainable, and robust manner. Many of the overall goals are set by projected commercial demand.
2023-Nov-08

Development of a Continuous Flow Grignard Reaction to Manufacture a Key Intermediate of Ipatasertib
The development of a continuous flow process for the manufacture of a key intermediate of the active pharmaceutical ingredient ipatasertib for the treatment of metastatic castration-resistant prostate cancer and triple-negative metastatic breast cancer.
2023-Nov-07

Selected highlights at AIChE Annual Meeting 2023
Links to abstracts of presentations featuring use of Scale-up Suite by Amgen, BMS, Hovione, Lilly, MSD (Merck), Sarafinas, Seagen, Snapdragon (Cambrex), Veranova.
2023-Oct-27

Automated End-to-End Workflow for Volumetric Mass-Transfer Coefficient (kLa) Characterization in Small-Molecule Pharmaceutical Development
Biocatalytic aerobic oxidations have recently emerged in the small-molecule pharmaceutical industry as a selective and green alternative to traditional chemocatalyzed oxidations that rely on transition-metal-based oxidants.
2023-Oct-19

Implementation of MSMPR Crystallization to Avoid Liquid–Liquid Phase Separation (LLPS)
The presence of metastable liquid–liquid phase separation (LLPS) near the solid–liquid equilibrium (SLE) is a common challenge encountered in the development of small-molecule crystallization.
2023-Sep-29

Development of a Mechanistic Amino Acid Activation Reaction Kinetics Model for Safe and Efficient Solid Phase Peptide Synthesis
Amino acid pre-activation is a critical reaction step during solid phase peptide synthesis due in part to the formation of impurities such as isomer, N,N′-diisopropylcarbodiimide-adduct and single amino acid addition.
2023-Sep-08

Development of a Control Strategy for Hydrogenation of Aryl Nitro Analogs by Kinetic Justification
This article describes the development of a control strategy for controlling potentially mutagenic impurities that result from the hydrogenation of aryl nitro analogs, utilizing concepts outlined in the International Conference on Harmonisation guidelines
2023-Sep-05

Synthesis of a Highly Functionalized Quinazoline Organozinc toward KRAS G12C Inhibitor Divarasib (GDC-6036), Enabled through Continuous Flow Chemistry
The development of a scalable continuous flow process to synthesize a densely functionalized quinazoline organozinc intermediate toward KRAS G12C inhibitor divarasib (GDC-6036) is reported herein.
2023-Aug-24

New Scale-Up Technologies for Multipurpose Pharmaceutical Production Plants: Use Case of a Heterogeneous Hydrogenation Process
Minimizing the effort associated with the pilot and laboratory-scale experiments needed for a successful scale-up of a process from laboratory to production scale is a significant challenge in process development.
2023-Jul-06

Development of a cellular mixing model for competitive-consecutive reactions
This work presents experimental and theoretical investigations into the effects of mixing on third-order reaction kinetics in a semibatch reactor with high feed rates.
2023-May-05

Copper-Catalyzed Racemization-Recycle of a Quaternary Center and Optimization Using a Combined Kinetics-DoE/MLR Modeling Approach
The copper-catalyzed racemization of a complex, quaternary center of a key intermediate on route to lanabecestat has been identified.
2023-Apr-17

Utilization of Quality by Design, Kinetic Modeling, and Computational Fluid Dynamics for Process Optimization and Scale-Up
Under acidic conditions, 16-α hydroxy prednisolone (16-AHP) reacts with n-butyraldehyde through acetalization and epimer conversion to produce budesonide. To further understand the conversion of epimers, a kinetic study was conducted.
2023-Apr-17

Case Studies in the Application of a Workflow-Based Crystallization Design for Optimized Impurity Rejection in Pharmaceutical Development
Crystallization is an important unit operation in pharmaceutical drug substance manufacturing for the isolation of organic products. Impurity control is a recurring critical quality attribute in most commercial pharmaceutical crystallization processes.
2023-Mar-24

Multivariate curve resolution for kinetic modeling and scale-up prediction
This paper describes the investigation of an imine synthesis reaction in an oscillating segmented flow microreactor. The reaction is profiled using in-line Raman spectroscopy, and the reaction kinetic modelled using Dynochem.
2023-Jan-31

Kinetic and Mechanistic Investigations to Enable a Key Suzuki Coupling for Sotorasib Manufacture─What a Difference a Base Makes
The process to manufacture sotorasib (AMG 510) employs a Suzuki–Miyaura reaction as a key step in the synthetic sequence.
2022-Dec-27

Selected highlights at AIChE Annual Meeting 2022
Links to abstracts of presentations featuring use of Scale-up Suite by BMS, Continuus, Gilead, GSK, Lilly, Merck, On Demand Pharma, Sanofi, Teich Process Development, Vertex, US Army
2022-Nov-03

Evaluation of Predictive Solubility Models in Pharmaceutical Process Development─an Enabling Technologies Consortium Collaboration
Solubility is an important property in the design of many unit operations within the development of synthetic pharmaceutical processes.
2022-Aug-22

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution
This review describes the practical aspects involved in the implementation of large-scale amidations in process chemistry. Coupling reagent, base, additive, and solvent selections are critically analyzed to highlight their pros and cons.
2022-Jun-07

Discovery and Process Development of a Scalable Biocatalytic Kinetic Resolution toward Synthesis of a Sterically Hindered Chiral Ketone
Sterically hindered chiral ketones are useful intermediates in the synthesis of active pharmaceutical ingredients.
2022-May-17

Spotlights: Unsafe Data Sheets, Fear Responses, and Virtual Continuous Manufacturing
Safety data sheets (SDSs) are intended to provide individuals and organizations with critical chemical safety information, but are rarely written by teams of experts.
2022-Apr-26

Advances in Continuous Flow Calorimetry
Calorimetric data from chemical reactions such as reaction enthalpy, adiabatic temperature rise, and activation energy are essential for reaction safety and scale-up from laboratory investigations to reactor design and operation.
2022-Jan-19

Considerations for safe operation of batch process at the boiling point
Key points to consider at high heat rates are solvent evaporated, level swell, flooding of condenser lines. The coupling reaction of aniline with cyanamide is looked at as a case study.
2021-Dec-09

Scalable Synthesis of (R,R)-N,N-Dibenzyl-2-fluorocyclohexan-1-amine with CsF under Hydrogen Bonding Phase-Transfer Catalysis
Hydrogen bonding phase-transfer catalysis offers a convenient solution to activate safe and economical metal alkali fluorides for enantioselective nucleophilic fluorination.
2021-Dec-03

Development of a High-Throughput Kinetics Protocol and Application to an Aza-Michael Reaction
A case study is presented with a transition metal salt/TMSCl-catalyzed aza-Michael reaction to showcase the performance and robustness of the high-throughput kinetic platform.
2021-Nov-24

Manufacturing Process Development for Belzutifan, Part 4: Nitrogen Flow Criticality for Transfer Hydrogenation Control
A scalable and efficient synthesis of hydroxyindanone, a key intermediate for belzutifan (MK-6482), is described.
2021-Nov-15

Manufacturing Process Development for Belzutifan, Part 6: Ensuring Scalability for a Deoxyfluorination Reaction
The development of a regio- and stereoselective deoxyfluorination process for the manufacture of belzutifan (MK-6482) was challenging because of a combination of particular reaction and engineering sensitivities.
2021-Nov-15

New Scale-up Technologies for Hydrogenation Reactions in Multipurpose Pharmaceutical Production Plants
With only a few laboratory-scale experiments and information about the production-scale reactor, a chemical
process model is developed. Collaboration between Siegfried and University of Applied Sciences and Arts Northwestern Switzerland.
2021-Nov-11

Selected highlights at AIChE Annual Meeting 2021
Links to abstracts of presentations featuring use of Dynochem or Reaction Lab by AbbVie, BMS, Hovione, Lilly, Merck, Sarafinas Process & Mixing Consulting.
2021-Nov-03

Step Up: Gas–Liquid Mass-Transfer Characterization at Plant Scale Using the Pressure Step Method
Gas–liquid reactions (such as aqueous phase hydrogenations) are frequently mass transport limited. Characterization of reactor overall mass transport performance is key to the successful transfer of reactions across scales or between plants.
2021-Oct-28

Continuous Multiphase Flow Nitration and Cryogenic Flow Formylation: Enabling Process Development and Manufacturing of Pharmaceutical Intermediates
Manufacturing API and pharmaceutical intermediates requires the development of scalable, safe, and environmentally friendly processes.
2021-Oct-28

Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions
An early synthetic step in the synthesis of adavosertib, AZD1775, is the SNAr reaction between 4-fluoronitrobenzene and 1-methylpiperazine in acetonitrile.
2021-Oct-25

Process Development, Manufacture, and Understanding of the Atropisomerism and Polymorphism of Verinurad
The manufacturing route toward verinurad, an amphoteric, class II atropisomer that readily forms solvates, has proven to be highly complex.
2021-Oct-25

Investigating the Activation Kinetics of Phosphoramidites for Oligonucleotide Synthesis
Solid-phase synthesis of oligonucleotides relies on a repeating cycle of rapid and well-defined synthetic steps to generate the target sequence.
2021-Oct-08

Guest: James Murray, Amgen: “Kinetic Modelling of Complex Organic Reactions; A Minimalist Approach"
Complex kinetic models often require extensive experimentation to provide predictive capabilities. Our approach to minimizing experimentation and producing simple yet functional models to accelerate process optimization will be discussed.
2021-Sep-08

Hydrogen Evolution from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Diboron Reagents: Process Safety and Hazard Considerations
The hazard assessment of a telescoped Miyaura borylation and Suzuki coupling reaction employing bis(pinacolato)diboron (BisPin), used in the developmental synthesis of an intermediate for abemaciclib, led to the observation of hydrogen being generated.
2021-Aug-06

Boron Trifluoride-Mediated Cycloaddition of 3-Bromotetrazine and Silyl Enol Ethers: Synthesis of 3-Bromo-pyridazines
Pyridazines are important scaffolds for medicinal chemistry or crop protection agents, yet the selective preparation of 3-bromo-pyridazines with high regiocontrol remains difficult.
2021-Aug-03

Augmenting Adaptive Machine Learning with Kinetic Modeling for Reaction Optimization
We combine random sampling and active machine learning (ML) to optimize the synthesis of isomacroin, executing only 3% of all possible Friedländer reactions.
2021-Jul-08

Guest: Moussa Boukerche and Akshay Korde, AbbVie: “Leveraging Dynochem to Enable Development of Robust Crystallization Processes prone to Liquid-Liquid Phase Separation (LLPS)"
Please see the "linked item" in Dynochem Resources to download the abstract.
2021-Jun-23

Development of a Scalable Synthetic Route to BMS-986251. Part 1: Synthesis of the Cyclohexane Dicarboxylate Fragment
The cyclohexane dicarboxylate unit of BMS-986251 (1), a potent and efficacious RORγt inverse agonist, was synthesized starting from Hagemann’s ester in seven chemical transformations with five isolated intermediates.
2021-Jun-15

Guest: Ronald Carrasquillo & Daniel Perkins, BMS: “Efficient Parameter Space Assessment to Enable the Scale Up of Mixing Operations (A picture is still worth 1000 words)”
We present case studies showing how easy to use scripts, which create response surface plots from rigorous Dynochem mixing calculations over the parameter space, drove good scale-up decisions at CMOs and overcame a preference for simple but costly DoEs.
2021-Jun-09

Abstract for Guest: Moussa Boukerche and Akshay Korde, AbbVie: “Leveraging Dynochem to Enable Development of Robust Crystallization Processes prone to Liquid-Liquid Phase Separation (LLPS)
Abstract for Guest Webinar
2021-May-26

Guest: Dries De Clercq, Ajinomoto Bio Pharma Services: “The optimization of centrifugation cycles"
During this guest webinar, the selection of the most optimal production scale centrifugation parameters (e.g. rotational speed, filter cake thickness, filter cloth and feed flowrate), using lab scale filtration data and DynoChem models will be discussed.
2021-May-12

Guest: Alessandro Agosti, Olon: “Right first time using Dynochem tools"
During this guest webinar, Alessandro will talk about examples of quick wins using Dynochem in a CDMO for scale-up and process optimization of typical API unit operations.
2021-Apr-14

Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge
The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities.
2021-Apr-14

Promoting a Safe Laboratory Environment Using the Reactive Hazard Evaluation and Analysis Compilation Tool
In the past several years, the U.S. Chemical Safety Board has found an increase in the frequency of laboratory accidents and injuries.
2021-Mar-01

Distance Teaching in Chemistry: Opportunities and Limitations
Remote teaching in the tertiary education sector is a relatively common practice, and the implementation of digital solutions in chemistry teaching offers many new opportunities and tools.
2021-Feb-28

Characterization of Propionyl Phosphate Hydrolysis Kinetics by Data-Rich Experiments and In-Line Process Analytical Technology
In-depth characterization of reaction kinetics often requires a considerable amount of experimental results under various conditions.
2021-Feb-17

Crystallization Process Development for the Final Step of the Biocatalytic Synthesis of Islatravir: Comprehensive Crystal Engineering for a Low-Dose Drug
Islatravir (MK-8591), a highly potent nucleoside reverse transcriptase translocation inhibitor, is being developed to stem the spread of global HIV infections.
2021-Jan-22

Guest: Bertrand Guelat, Novartis: “Direct flow calorimetry to facilitate the scale-up of continuous processes"
Bertrand will present the approach of Novartis Continuous Manufacturing team for flow calorimetry in a Fluitec reactor with the Dynochem PFR model for heat balance as a frame to support scale-up to manufacturing scale.
2021-Jan-13

Development of a Scalable Negishi Cross-Coupling Process for the Preparation of 2-Chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)aniline
A scalable synthesis of 2-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)aniline (1), a key intermediate in the synthesis of an immuno-oncology asset, is described.
2020-Dec-23

Guest: Cheryl Teich, Teich Process Development: “Process Schemes and the 'Yoga of Process Development'"
Cheryl Teich (former AIChE President, Yoda of Process Schemes and yoga enthusiast) shows how to use a simple diagram to start your journey to process understanding on the right foot, as opposed to the left foot.
2020-Dec-09

Efficient Process Development in the Micromixing-Mesomixing Space: the Bourne Protocol and Beyond
Slides and accompanying notes from Aaron Sarafinas’s 2020 AIChE Annual meeting presentation – paper 426d
2020-Nov-18

Selected highlights at AIChE Annual Meeting 2020
Links to abstracts of presentations including Dynochem work by AbbVie, APC, Blackthorn Therapeutics, BMS, Hovione, Merck, Sarafinas Process & Mixing Consulting, Vertex.
2020-Nov-12

Guest: Keith Mattern, Merck: “End-to-End Automation: Characterizing volumetric mass transfer coefficient (kLa) across process scales using Dynochem"
Application of automated platform for experimental execution and model regression of gas-liquid mass transfer for reactor characterization, scale-up of biocatalytic oxidation. Review of Dynochem model development to capture unique system dynamics. mAbs.
2020-Nov-11

Process Safety in the Pharmaceutical Industry—Part I: Thermal and Reaction Hazard Evaluation Processes and Techniques
Process safety groups in the pharmaceutical industry are important components of active pharmaceutical ingredient (API) development through its life cycle from discovery to commercial scale.
2020-Oct-24

Crystallization Process Modifications to Rapidly Address Polymorphic and Particle Size Challenges in Early Stage Development of an API Salt
A case study highlighting the risk of generating undesired hydrate polymorph following seeded distillative crystallization of an active pharmaceutical ingredient (API) from aqueous alcoholic solution and a strategy to overcome the issue is presented.
2020-Sep-22

Activation of C–O and C–N Bonds Using Non-Precious Metal Catalysis
Activation of C–O and C–N Bonds Using Non-Precious Metal Catalysis
2020-Sep-10

Kinetics, Thermodynamics, and Scale-Up of an Azeotropic Drying Process: Mapping Rapid Phase Conversion with Process Analytical Technology
Distillation processes with several solid-state phases and dynamic multicomponent liquid-phase compositions can be challenging to understand and scale up because of complexity of the thermodynamics combined with process dynamics and kinetics.
2020-Aug-20

Guest: Christopher Wilbert & Carlos Pons-Siepermann, BMS: “Applying Dynochem Tools in the Design and Analysis of a Complex Continuous Crystallization Problem"
Via continuous crystallization, we captured a steady state that avoids a meta-stable liquid-liquid phase in a small-molecule system. Explores the steps required to develop this process and Dynochem tools implemented for analysis and design. MSMPR, LLPS
2020-Aug-12

CFD approach for simulation of API release from solid dosage formulations
A comprehensive mathematical model has been developed to study release behaviour of Active Pharmaceutical Ingredients (API) from pharmaceutical solid dosage oral formulations.
2020-Jul-25

Kinetic Investigations To Enable Development of a Robust Radical Benzylic Bromination for Commercial Manufacturing of AMG 423 Dihydrochloride Hydrate
During development of a radical benzylic bromination, observation of polymerized byproducts and variation in isolated yields warranted an in-depth mechanistic investigation to ensure process understanding and robustness.
2020-Jul-15

A Virtual Plant for Integrated Continuous Manufacturing of a Carfilzomib Drug Substance Intermediate, Part 1: CDI-Promoted Amide Bond Formation
This article details process characterization efforts and the development of corresponding process models to inform a process control strategy to produce a carfilzomib drug substance intermediate, morpholine amide 3.
2020-Jul-14

A Virtual Plant for Integrated Continuous Manufacturing of a Carfilzomib Drug Substance Intermediate, Part 2: Enone Synthesis via a Barbier-Type Grignard Process
This article details efforts to characterize and develop a process control strategy for the manufacture of enone 2, a carfilzomib drug substance intermediate obtained through a Barbier-type Grignard reaction of morpholine amide 1.
2020-Jul-14

A Virtual Plant for Integrated Continuous Manufacturing of a Carfilzomib Drug Substance Intermediate, Part 3: Manganese-Catalyzed Asymmetric Epoxidation, Crystallization, and Filtration
This article describes the process characterization and development of models to inform a process control strategy to prepare (R,R)-epoxy ketone 2, an intermediate in the manufacture of carfilzomib.
2020-Jul-14

Reaction Calorimetry in Continuous Flow Mode: A New Approach for the Thermal Characterization of High Energetic and Fast Reactions
A new method for the calorimetric characterization of high-energetic, fast reactions in flow mode was developed.
2020-Jul-07

Self-optimising processes and real-time-optimisation of organic syntheses in a microreactor system using Nelder–Mead and design of experiments
Optimisation problems are abundant both in lab and industrial chemistry, where the determination of ideal reaction conditions poses particular challenges.
2020-Jun-15

Development and Execution of an Ni(II)-Catalyzed Reductive Cross-Coupling of Substituted 2-Chloropyridine and Ethyl 3-Chloropropanoate
We describe the development and scale-up of a nickel-catalyzed reductive cross-electrophile coupling reaction between a substituted 2-chloropyridine and ethyl 3-chloropropanoate using manganese dust as the terminal reductant.
2020-May-18

Efficient Kinetic Data Acquisition and Model Prediction: Continuous Flow Microreactors, Inline Fourier Transform Infrared Spectroscopy, and Self-Modeling Curve Resolution
This work presents and evaluates an approach to obtain and model kinetic data by combining a microreactor setup and real-time reaction monitoring through inline Fourier transform infrared spectroscopy with nonsteady-state conditions and SMCR.
2020-Apr-14

Efficient Kinetic Data Acquisition and Model Prediction: Continuous Flow Microreactors, Inline FT-IR Spectroscopy, and Self-modeling Curve Resolution
This work presents and evaluates an approach to obtain and model kinetic data by combining a microreactor setup and real-time reaction monitoring through inline FT-IR spectroscopy with nonsteady-state conditions and self-modeling curve resolution (SMCR).
2020-Apr-14

Guest: Jeremy Merritt, Eli Lilly: “Applications of In Silico Solvent Screening and an Interactive Web-Based Portal for Pharmaceutical Crystallization Process Development”
A web portal and parallelized platform were built for API solvent selection and crystallization design. Jeremy will show its use for several projects and development stages. After 1 year, average per project savings were ~10x API use and 20% FTE time.
2020-Mar-11

Guest: Kirankumar Ramisetty, University of Limerick / SSPC: "Seeded crystal growth kinetics from the population balance model in Dynochem"
Kirankumar will talk about some of his Post Doc work on using Dynochem for modelling crystallization as part of the SSPC project.
2019-Dec-11

Efficiently characterize Process Scalability in the Micromixing-Mesomixing Space using the Bourne Protocol
Slides and accompanying notes from Aaron Sarafinas’s 2019 AIChE Annual meeting presentation – paper 470g
2019-Nov-13

Selected highlights at AIChE Annual Meeting 2019
Links to abstracts of presentations including Dynochem work by AbbVie, Alkermes, BMS, Hovione, Merck, Sarafinas Process & Mixing Consulting & Scale-up Systems.
2019-Nov-07

Guest: Lauren McCullough, Dow: "Using DynoChem to Advance Process Insight with Limited Data"
Lauren will discuss using DynoChem to squeeze process insight from limited plant and experimental data for performance and safety evaluations.
2019-Oct-23

Optimization of an Azaindazole Series of CCR1 Antagonists and Development of a Semicontinuous-Flow Synthesis
Chemotactic cytokine receptor 1 (CCR1) is involved in trafficking of immune cells to sites of inflammation. Antagonism of CCR1 has been extensively explored as an approach to treat inflammatory and autoimmune disease.
2019-Sep-27

Guest: Joe Harris, Johnson Matthey: "Crystallization Development in the Salt/Cocrystal Continuum – Use of PAT and DynoChem Modelling for Crystallization of a Metastable Form"
The presentation will focus on use of Dynochem simulation with PAT in crystallization process development
2019-Sep-11

Follow the Silyl Cation: Insights into the Vorbrüggen Reaction
To succeed in the development of a mechanistic model for the Vorbrüggen reaction of thymine with an advanced furanose intermediate, a range of spectroscopic techniques were applied and found essential to understanding kinetically relevant.
2019-Aug-21

Bayesian probabilistic modeling in pharmaceutical process development
Bayesian probabilistic modeling in pharmaceutical process development
2019-Aug-20

Model-Based Scale-Up Predictions: From Micro- to Millireactors Using Inline Fourier Transform Infrared Spectroscopy
Scale-up predictions from a continuous flow micro- (lab) to milliscale (pilot or production) are important but not trivial. To overcome the necessity of time-consuming trials on the pilot or production scale, this work presents a model-based approach.
2019-Aug-07

Guest: Flavien Susanne, GSK: "How Process Simulation can Influence the Process Development and Control Strategy of a Drug Substance Asset"
At GSK, supported by a new modelling strategy, we are now embedding mechanistic and first principal models to support the process development phase and the control strategy of drug substance continuous processes from laboratory to manufacture.
2019-Jul-22

Guest: James Marek and Eric Moschetta, AbbVie: "Improving Process Development Workflows and Kinetic Understanding through PAT"
Please see (https://aiche.confex.com/aiche/2018/meetingapp.cgi/Paper/529180) and (https://aiche.confex.com/aiche/2018/meetingapp.cgi/Paper/529073)
2019-Jul-10

Development of an Operational Space Using Mechanistic Models for a Pd-Catalyzed Amidation Reaction Used in the Synthesis of ABT-530
Rigorous understanding of the impact of reaction parameters on the formation and rejection of impurities in a reaction is a critical part of process development.
2019-Jul-01

Talking Mixing: Reactive Mixing
Aaron Sarafinas introduces best practice methodologies for scale-up of mixing sensitive reactions and provides advice based on academic theory and real world applications
2019-Jun-19

In Situ Reaction Monitoring of Unstable Lithiated Intermediates through Inline FTIR Spectroscopy
Because a multitude of reactions with n‐butyllithium are of high industrial significance, an in‐depth process understanding is required to render potential scale‐up from the laboratory to production more efficient.
2019-Jun-12

Definitive screening designs for multistep kinetic models in flow
Currently, rate-based understanding of organic reactions employed in the manufacture of active pharmaceutical ingredients (APIs) is often not obtained.
2019-Jun-06

Talking Mixing: Multiphase Mixing
Aaron Sarafinas introduces some important parameters and provided advice for successful design and scale-up of mixing in stirred tank reactors with heterogeneous phases, e.g. solid-liquid or immiscible liquids
2019-May-29

Advanced Size Distribution Control in Batch Cooling Crystallization Using Ultrasound
The combination of a small sonicated crystallizer operated as a seed generator with a large normal batch cooling crystallizer for growth of the seeds has been investigated.
2019-Apr-25

Talking Mixing: Basics of Mixing
Aaron Sarafinas introduces some basics of mixing in agitated reactors from lab scale to production, such as flow, shear and blending; providing advice and drawing on international research and his own practical experiences in scale-up and optimization
2019-Apr-24

Applications of In Silico Solvent Screening and an Interactive Web-Based Portal for Pharmaceutical Crystallization Process Development
In an effort to reduce development time and costs associated with active pharmaceutical ingredient process solvent selection and crystallization design.
2019-Mar-21

Effects of Scale, Equipment, and Operation on Agglomeration during a Reactive Crystallization
Developing processes to deliver formulation-ready active pharmaceutical ingredients (APIs) in a robust and consistent manner comes with challenges.
2019-Feb-25

Process Intensification Strategies and Sustainability Analysis for Amidation Processing in the Pharmaceutical Industry
The amidation reaction between 4-chlorobenzoyl chloride (CBC) and diisopropylamine (DIPA) has been successfully intensified with the implementation of a number of process intensification (PI) options proven feasible in lab-scale experiments.
2019-Feb-21

An Introduction to Closed‐Loop Process Optimization and Online Analysis
An Introduction to Closed‐Loop Process Optimization and Online Analysis
2019-Jan-24

The Role of Residence Time Distribution in the Continuous Steady-State Mixed Suspension Mixed Product Removal Crystallization of Glycine
In this work, a vacuum-driven intermittent transfer technique has been implemented to solve transfer line blockage issues and facilitate steady-state cooling crystallization studies of α-glycine in a single- and two-stage MSMPR crystallizer.
2018-Nov-15

Guest: Claire MacLeod, AstraZeneca: “Use of the Dynochem centrifuge model to scale-up from lab to plant”
Claire will discuss scale-up of centrifugation processes from laboratory filtration data using DynoChem modelling tools
2018-Nov-14

Process Development of a Suzuki Reaction used in the Manufacture of Lanabecestat
We have developed a scalable Suzuki process towards the synthesis of lanabecestat (+)-camsylate, an active pharmaceutical ingredient that was recently investigated in a Phase III clinical program for the treatment of early Alzheimer’s Disease.
2018-Nov-07

Selected highlights at AIChE Annual Meeting 2018
Links to abstracts of presentations including DynoChem work by AbbVie, Dow, FDA, Hovione, Lilly, Merck, Pfizer, Zoetis
2018-Oct-23

Continuous‐flow Synthesis of Aryl Aldehydes by Pd‐catalyzed Formylation of Aryl Bromides Using Carbon Monoxide and Hydrogen
A continuous‐flow protocol utilizing syngas (CO and H2) was developed for the palladium‐catalyzed reductive carbonylation of (hetero)aryl bromides to their corresponding (hetero)aryl aldehydes.
2018-Oct-09

Evaluation of Just-Suspended Speed Correlations in Lab-Scale Tanks with Varying Baffle Configurations
Suspension of insoluble solids in stirred tanks is important for many operations in the pharmaceutical and specialty chemical industries.
2018-Oct-01

Guest: Barbara Wood, UCD Crystallization Group: "Utilizing DynoChem Modelling to Design the Continuous Crystallization of an Active Pharmaceutical Ingredient - Part II"
Barbara will build on her previous presentation with model development from further continuous crystallization experiments, including scale-up.
2018-Sep-12

Guest: Aaron Sarafinas, Sarafinas Process & Mixing Consulting: "Using the "Bourne Protocol" to test mixing sensitivities in the lab"
This webinar will discuss an example from Advances in Industrial Mixing where we applied the “Bourne Protocol” in a Mettler-Toledo RC-1e™ calorimeter and identified critical mixing sensitivities in a reactive crystallization.
2018-Aug-08

Effects of Scale-Up on the Mechanism and Kinetics of Crystal Nucleation
Insight into nucleation kinetics and other nucleation parameters can be obtained from probability distributions of induction time measurements in combination with the classical nucleation theory.
2018-Aug-08

Guest: Tom Corrie, Syngenta: “Accelerating Active Ingredient Development with Early Stage DynoChem Simulations”
This talk will cover the implementation of DynoChem in agrochemical process development as a resource for knowledge generation and project direction in time-restricted projects, where extensive experimentation is not possible.
2018-Jul-11

Stereoretentive Etherification of an α-Aryl-β-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594
A selective aziridinium ring-opening was used to etherify an α-aryl-β-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity.
2018-Jun-19

Guest: Li-Jen Ping Johnson Matthey Pharma Services: "Minimize the Heat Accumulation at Production Scale by Modeling Qr of Exothermic Reaction "
Reaction model built with data from calorimetry experiments enables prediction of optimal peroxide feed rate on scale-up of exothermic reaction to control heat accumulation within the production reactor capabilities.
2018-Apr-11

Process design methodology for organometallic chemistry in continuous flow systems
This publication summarises the methodology applied in the process design and scale up of fast, exothermic reactions using organometallic reagents for synthesis of intermediates in the production of Active Pharmaceutical Ingredient (API).
2018-Apr-07

Guest: Orel Mizrahi, Teva & Ariel University: "Control of Crystallization PSD using DynoChem Simulation"
Development and validation case study of a predictive QMOM model for the final crystallization step of Rasagiline mesylate.
2018-Feb-21

Guest: Andrew Cosbie, Amgen and Matt Jorgensen, NALAS Engineering: "Dynamic Modeling of Intermediate and API Drying Operations"
The characterization of drying kinetics for an API and isolated intermediates through the use of the Schlunder model is discussed. Work flow and experimental methods are shared and comparison of model simulations to actual plant performance is reviewed.
2018-Feb-14

High-Throughput Automated Design of Experiment (DoE) and Kinetic Modeling to Aid in Process Development of an API
A Design of Experiment (DoE) and kinetic screening study was carried out using an automated reaction screening platform, and as a case study, an early stage in the synthesis of a late phase developmental candidate was investigated.
2017-Dec-14

Development of a Safe and Scalable Process for the Preparation of Allyl Glyoxalate
While conversion of dialkyl tartrate esters to the corresponding glyoxalic acid esters has been well-documented, large scale application of some common laboratory protocols presents a myriad of challenges.
2017-Dec-06

Selected highlights at AIChE Annual Meeting 2017
Links to abstracts of DynoChem presentations by BMS, Merck, UCD Dublin, Hovione, AbbVie, APC, GSK
2017-Oct-23

Guest: Laszlo Tamas, TEVA "Using DynoChem to support the development of Biotechnology-based semi-synthetic API Production"
Dr Laszlo Tamas will talk about the role of process modelling using DynoChem in his work and will illustrate this with examples from API process development and scale-up, mAbs
2017-Oct-18

Development of a Robust and Reusable Microreactor Employing Laser Based Mid-IR Chemical Imaging for the Automated Quantification of Reaction Kinetics
A robust, reusable microreactor coupled with laser based mid-IR chemical imaging and automated analysis is reported, for the first time, with its application to monitor and quantify fast organometallic chemistry in flow.
2017-Oct-13

Match-Making Reactors to Chemistry: A Continuous Manufacturing-Enabled Sequence to a Key Benzoxazole Pharmaceutical Intermediate
The focus of this study was to develop a chemical reaction sequence toward a key benzoxazole building block, required for clinical manufacturing of a lead candidate in the respiratory disease area.
2017-Oct-09

Development of a Leuckart-Wallach Reaction in Flow for the Synthesis of Abemaciclib
The development of a route for a key building block in the synthesis of abemaciclib is described. The route proceeds through a Leuckart–Wallach reductive amination in flow followed by an Ullmann amination with aqueous ammonia. PFR.
2017-Aug-16

Guest: Lotfi Derdour, GSK: "Use of Dynochem to estimate kinetics parameters for reactive salting out crystallizations"
Discusses the use of predictive modeling to gain a better understanding of processes and reduce the number of experiments required for process development and optimization. Using DynoChem precipitation model.
2017-Aug-09

Mechanistic investigation of a Ru-catalyzed direct asymmetric reductive amination reaction for a batch or continuous process scale-up: an industrial perspective
A comprehensive assessment of a Ru-catalyzed direct asymmetric reductive amination (DARA) reaction for producing an intermediate for an active pharmaceutical ingredient (API) was carried out. PFR.
2017-Aug-08

Screwing NaBH4 through a Barrel without a Bang: A Kneaded Alternative to Fed-Batch Carbonyl Reductions
In this work the application of green chemistry principles such as process intensification and the replacement of reagents and solvents to more benign alternatives were coupled with the advantages of continuous manufacturing.
2017-Jul-22

Guest: Anuj Verma, Abbvie "Using Dynochem Mixing utilities to ensure safe scale-up of a highly exothermic mixing limited reaction"
Slides from guest webinar of 12 July 2017
2017-Jul-12

Modeling reduces nickel needed in catalytic reactions
Nickel catalysts are much less expensive than precious metal catalysts, but the large amounts of nickel catalyst used in many catalytic cross-coupling reactions still discourage industrial adoption.
2017-Jun-19

Guest: Bruno De Kort, Monsanto "Evaluating runaway reaction scenarios during scale up to large scale using DynoChem"
Slides from guest webinar of 14 June 2017
2017-Jun-14

Recent Developments in the Crystallization Process: Toward the Pharmaceutical Industry
Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building efficient manufacturing processes.
2017-Jun-08

Kinetic Modeling of the Nickel-Catalyzed Esterification of Amides
Nickel-catalyzed coupling reactions provide exciting tools in chemical synthesis. However, most methodologies in this area require high catalyst loadings, which commonly range from 10–20 mol % nickel.
2017-May-22

Guest: Barbara Wood, University of Limerick "Utilizing Dynochem Modelling to Design the Continuous Crystallization of an Active Pharmaceutical Ingredient"
Slides from guest webinar of 10 May 2017. MSMPR. CSTRs in series.
2017-May-10

Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations
The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations.
2017-Apr-03

Guest: Roel Hoefnagels, Janssen "Development of Modeling Enhanced Work Streams to Optimize the Scale-up of Solvent Switches"
Slides from guest webinar of 15 March 2017
2017-Mar-15

The Pharmaceutical Drying Unit Operation: An Industry Perspective on Advancing the Science and Development Approach for Scale-Up and Technology Transfer
The drying unit operation is used extensively in the pharmaceutical industry, but often a lack of understanding of the impact of the drying process parameters on active pharmaceutical ingredient critical quality attributes can create challenges.
2017-Feb-03

The Development of a Dimroth Rearrangement Route to AZD8931
Recently, the aminoquinazoline motif has been highly prevalent in anticancer pharmaceutical compounds. Synthetic methods are required to make this structure on a multikilo scale and in high purity.
2017-Feb-01

Development and Scale-up of a Biocatalytic Process To Form a Chiral Sulfoxide
A Baeyer–Villiger monooxygenase enzyme has been used to manufacture a chiral sulfoxide drug intermediate on a kilogram scale.
2017-Jan-04

Development of a concise, scalable synthesis of a CCR1 antagonist utilizing a continuous flow Curtius rearrangement
A convergent, robust, and concise synthesis of a developmental CCR1 antagonist is described using continuous flow technology. In the first approach, following an expeditious SNAr sequence for cyclopropane introduction, a safe, continuous flow ...
2017-Jan-03

Measurement and prediction of dabigatran etexilate mesylate Form II solubility in mono-solvents and mixed solvents
UV spectrometer method was used to measure the solubility data of dabigatran etexilate mesylate (DEM) Form II in five mono-solvents (methanol, ethanol, ethane-1,2-diol, DMF, DMAC) and binary solvent mixtures of methanol and ethanol.
2016-Dec-15

Guest: Sandra Lenihan, CIT "Incorporating DynoChem Process Simulation Software into a Chemical Engineering Programme"
Dr Sandra Lenihan talks about how DynoChem has been used to support experimental labs, teaching and final year design projects at Cork Institute of Technology.
2016-Nov-30

Characterization of Lab and Plant Reactors Using Fast Competitive Reactions and a Predictive Model
Andrew and Joe present further experimental data and DynoChem model predictions to characterize mesomixing and micromixing in lab and plant reactors.
2016-Nov-16

Selected highlights at AIChE Annual Meeting 2016
Links to abstracts of DynoChem presentations by Hovione, BMS, Nalas, APC, UCD Dublin, UL Limerick, SSPC, Lilly, Pfizer, Abbvie, GSK
2016-Nov-04

Practical Synthesis of MDM2 Antagonist RG7388. Part 2: Development of the Cu(I) Catalyzed [3 + 2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin
A concise catalytic asymmetric synthesis of idasanutlin (1) was developed in which the key pyrrolidine core, containing four contiguous stereocenters, was constructed via a Ag/MeOBIPHEP promoted [3 + 2] cycloaddition reaction.
2016-Oct-31

Guest: Andrew Derrick, Pfizer "Characterization of Mixing in Reactors", Part 2
Andrew and Joe present experimental data and DynoChem model predictions to characterize mixing in lab and plant reactors. Easymax, RC1, Pilot. Bourne reactions.
2016-Oct-26

Development of a Control Strategy for a Final Intermediate to Enable Impurities Control
This manuscript describes the development of a control strategy for impurities in the final intermediate step of the asunaprevir drug substance utilizing the concepts outlined in the International Conference on Harmonisation guidelines.
2016-Oct-07

Rapid multistep kinetic model generation from transient flow data
oday, the generation of kinetic models is still seen as a resource intensive and specialised activity. We report an efficient method of generating reaction profiles from transient flows using a state-of-the-art continuous-flow platform.
2016-Oct-03

The scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions: methodology and reactor design
Biphasic liquid/liquid reactions are commonplace, however their scale-up under super-heating conditions is not.
2016-Sep-02

Guest: Nir Haimovich, TEVA "DynoChem in TEVA API: training colleagues for optimized use & implementation"
Computational tools used in API Product Life-Cycle; Vision; Basic Training in TEVA API; Rxn Kinetics / RC1 data: leveraged for global training. DynoChem in-house Advanced Training; Success stories; Power User community.
2016-Aug-10

Guest: Andrew Derrick, Pfizer & Joe Hannon: Characterization of Mixing in Reactors, Part 1
Andrew and Joe present experimental data and DynoChem model predictions to characterize mixing in lab and plant reactors. Easymax, RC1, Pilot. Bourne reactions. Feed position.
2016-Jul-01

A Scalable Synthesis of 2-(1,2,4-Oxadiazol-3-yl)propan-2-amine Hydrobromide Using a Process Safety-Driven Protecting Group Strategy
A safe and scalable synthesis of 2-(1,2,4-oxadiazol-3-yl)propan-2-amine hydrobromide is described.
2016-Jun-15

Guest: Marimuthu Andiappan, Lilly: Use of DynoChem Modeling for Process Design: Mitigating the Risk of Coprecipitation
How Lilly used process modeling to develop an effective control strategy to mitigate the unexpected precipitation of pinacol while telescoping a class of reactions.
2016-Jun-08

O-Phenylisourea Synthesis and Deprotonation: Carbodiimide Elimination Precludes the Reported Chapman Rearrangement
The kinetics of the addition of phenol to diisopropylcarbodiimide, and reaction of the resulting N,N′-diisopropyl-O-phenylisourea with hydroxide, are reported.
2016-May-23

Palbociclib Commercial Manufacturing Process Development. Part I: Control of Regioselectivity in a Grignard-Mediated SNAr Coupling
This manuscript focuses on the SNAr coupling between aminopyridine 3 and chloropyrimidine 7.
2016-May-12

Investigation of Reaction Kinetics using PAT and DynoChem
Investigation of Reaction Kinetics using PAT and DynoChem
2016-Apr-19

Investigation of Variable Impurity Profile from a Mitsunobu Reaction Using Insights from Kinetic Modeling, Multi-Phase Interactions, and Computational Fluid Dynamics
A drug substance intermediate synthesis involving a Mitsunobu coupling reaction using triphenylphosphine and diisopropyl azodicarboxylate was investigated to understand the variable levels of an impurity.
2016-Apr-11

Industrial Crystallization in China
The latest developments of industrial crystallization in China are reviewed. This includes the introduction of representative scientists and institutions promoting the progress of Chinese industrial crystallization
2016-Apr-09

Guest: Daniel Caspi, AbbVie: Development and Scale-up of Acrylamide Formation Using an Impinging Jet
Reaction kinetics and response surface simulations were used to reduce the chloro impurity to acceptable levels in a fit-for-purpose flow chemistry solution.
2016-Feb-10

Mitigating the Risk of Coprecipitation of Pinacol during Isolation from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Boron Pinacol Esters: Use of Modeling for Process Design
A Quality by Design (QbD) approach was used to illustrate the control strategy and provide a maximally flexible process for manufacturing to maintain high purity of the intermediate.
2015-Dec-21

Guest: Samrat Mukherjee, AbbVie: Model-Based Process Control in API Manufacturing: A QbD-Vantage!
In this guest webinar, Samrat Muhjerjee, Associate Director at AbbVie, discusses how Quality-by-Design in API synthesis is facilitated by the use of DynoChem models.
2015-Dec-09

Selected highlights at AIChE Annual Meeting 2015
Links to abstracts of DynoChem presentations by Lilly, Abbvie, APC, Merck, GSK, Nalas, Pfizer and Hovione
2015-Nov-26

Mono- and tri-ester hydrogenolysis using tandem catalysis. Scope and mechanism
The scope and mechanism of thermodynamically leveraged ester RC(O)O–R′ bond hydrogenolysis by tandem metal triflate + supported Pd catalysts are investigated both experimentally and theoretically by DFT and energy span analysis.
2015-Nov-26

Guest: Shujauddin Changi, Eli Lilly: Model and Experimental Driven Approach to Develop and Innovate Batch & Continuous Process Development for Grignard Reactions
Changi describes a strategy for using experiments and DynoChem kinetic models to develop Grignard reactions for batch and continuous operation, and shares an example where this approach was used to deliver a safe, robust process at commercial scale.
2015-Nov-04

Kinetics Model for Designing Grignard Reactions in Batch or Flow Operations
This paper describes the development of a “fit for use” model for a Grignard reaction, which was used to produce an intermediate compound during the manufacture of API for edivoxetine hydrochloride.
2015-Oct-29

Guest: Chris Pink, GSK: Ensuring consumption of a genotoxic starting material in API manufacture through kinetics and mixing studies
Slides from webinar on Ensuring Consumption of a Genotoxic Starting Material in API Manufacture through the use of Kinetics and Mixing Studies
2015-Oct-14

Guest: Chris Hone, University of Leeds: Evolution and Validation of Kinetic Motifs using Continuous-Flow Reactors
Chris Hone presents an example of how DynoChem is used for continuous flow reactor (PFR) design from his PhD work in Chemical Process Research and Development at iPRD, University of Leeds.
2015-Oct-07

A Kinetics-Based Approach for the Assignment of Reactivity Purge Factors
The control of mutagenic impurities is of crucial interest to pharmaceutical companies and regulatory agencies alike.
2015-Oct-05

Guest: Prof. Rex Reklaitis, Purdue University "A Course of Batch Process Design and Analysis using DynoChem"
In this guest webinar, Professor Reklaitis presented an example of how DynoChem is used in academia for teaching by members of the Academic Program.
2015-Sep-25

Impurity Profiling, Kinetics, and Representative Sampling from Reaction Slurries.
Adobe Presenter format presentation featuring use of the EasySampler with DynoChem.
2015-Sep-24

Rapid Decision Making Enabled Through Chemical Process Intensification.
Adobe Presenter format presentation featuring applications of DynoChem utilities and models for process intensification.
2015-Sep-24

Guest: Shane Grosser, Merck: Development and Scale up of Gas-Liquid Systems Facilitated through Process Modeling
Case studies using DynoChem to develop and scale up gas-liquid systems: pressure swings to dry and degas solvents; solvent evaporation to reduce reaction by-products; vessel characterization and optimization of a biocatalytic oxidation.
2015-Aug-12

Guest: Georges Assaf, UCB: Modelling Acid-Base Equilibria using DynoChem: Acid-Catalysed Condensation
A case study demonstrating the use of DynoChem to generate better understanding of acid-catalysed reaction from a mechanistic basis and optimization of yield.
2015-Aug-12

Application of Safety by Design Methodology in Evaluating Process Safety for a Duff Reaction Using Predictive Process Simulators
This work presents a Safety by Design (SbD)-driven approach to the evaluation of process safety and reaction modeling that was effective in obtaining enhanced process knowledge and defining a design space for chemical reaction hazards.
2015-Jul-30

Solid–Liquid Suspension in Pilot Plants: Using Engineering Tools to Understand At-Scale Capabilities
To address time lost due to inadequate assessment and understanding of solid suspension issues, empirical studies were conducted at pilot scale using a calcium carbonate and deionized water (DIW) system.
2015-Jul-14

Appearance of a New Hydrated Form during Development: A Case Study in Process and Solid-State Optimization
The appearance of a new solid phase during the development of a small molecule presents significant challenges for optimizing form control during crystallization and mitigating potential delays in development timelines.
2015-Jun-26

Design of Safe Energetic Process Using the Advanced Flow Reactor
Conventional manufacturing of energetic materials includes the use of batch and semi-batch reactors. These methods offer flexibility at the cost of safety, reproducibility and often times higher cost products.
2015-Jun-16

Guest: Ben Cohen, BMS: Use of Solubility Maps to Develop Robust Crystallizations
A case study demonstrating the use of DynoChem and high-throughput experimentation to construct a reliable solubility map for defining and optimizing crystallization process conditions.
2015-Jun-03

Using Data-Rich Experimentation to Enable the Development of Continuous Processes

2015-May-20

IR and NMR Reaction Monitoring Techniques for Nucleophilic Addition Reactions: In Situ Monitoring of the Addition of Benzimidazole to a Pyridinium Salt
This study centers on the use of in situ FTIR spectroscopy and online NMR to study the nucleophilic addition of benzimidazole analogues to an N-methylpyridinium salt. The reaction consists of two stages.
2015-Mar-30

Mechanism of Phosphine Borane Deprotection with Amines: The Effects of Phosphine, Solvent and Amine on Rate and Efficiency
The kinetics of borane transfer from simple tertiary phosphine borane adducts to a wide range of amines have been determined.
2015-Feb-20

Guest: Mannheim University of Applied Science: Kinetic Studies in Microreactors - Requirements for reliable data and successful reactor scale-up
Slides from DynoChem Guest Webinar by Thorsten Roder of Hochschule Mannheim, held on 19 November 2014
2014-Dec-10

Method for prediction of pharmaceutical solubility for solvent selection
Presentation at AIChE Annual Meeting 2014 on the Regressed UNIFAC method for solubility prediction
2014-Dec-10

Development of Flow Processes for the Syntheses of N-Aryl Pyrazoles and Diethyl Cyclopropane-cis-1,2-dicarboxylate
N-Aryl pyrazoles were prepared from anilines in a three step telescoped approach. An aniline was diazotized to give the diazonium fluoroborate, followed by reduction with tin(II) chloride to give the corresponding hydrazine.
2014-Nov-20

Selected highlights at AIChE Annual Meeting 2014
List and links to presentations by and of interest to DynoChem users at AIChE 2014, including AbbVie, BMS, GSK, Lilly, Nalas Engineering, Pfizer, Scale-up Systems
2014-Nov-19

Kinetic and Scale-up Investigations of a Michael Addition in Microreactors
Process development using microreactors (PFR) for an exothermic Michael addition is presented using DynoChem tools. This includes consideration of the assumption of ideal plug flow, local mixing at the feed point and heat transfer.
2014-Oct-14

Development of a Continuous Plug Flow Process for Preparation of a Key Intermediate for Brivanib Alaninate
A continuous (PFR) process was developed using both Qr and composition data to mitigate the potential thermal runaway and allow for safer scale-up.
2014-Oct-14

Guest: Nick Falco, GSK: Development of an ammonolysis reaction kinetics model for improved process understanding and parametric flexibility
Development of an ammonolysis reaction kinetics model in Dynochem and use of the model to improve the manufacturing process and define parametric flexibility in the operating space
2014-Sep-17

Development of a Modeling-Based Strategy for the Safe and Effective Scale-up of Highly Energetic Hydrogenation Reactions
A modeling-based strategy is disclosed for identifying reaction conditions for the safe and effective scale-up of highly energetic hydrogenation reactions.
2014-Aug-30

Guest: Sarah Rothstein, Nalas Engineering: Kinetic and manufacturing evaluations of 2,6-diaminopyrazine-1-oxide (DAPO) production
Development of a DynoChem kinetic model to study starting material decomposition, impurity formation, evaluate manufacturing options, and compare batch vs. continuous operation
2014-Aug-20

Fed-batch strategies using butyrate for high cell densitycultivation of Pseudomonas putida and its use as a biocatalyst
A mathematically based fed-batch bioprocess demonstrated
the suitability of using a relatively cheap and renewable
substrate (butyric acid) for Pseudomonas putida CA-3
high cell density cultivation.
2014-Aug-08

In-situ Analyses of Unstable Compounds in Batch and Flow Conditions
In-situ analyses using React-IR were applied to several reactions. Kinetics were fitted using DynoChem.
2014-Jul-31

Application of Kinetic Modeling and Competitive Solvent Hydrolysis in the Development of a Highly Selective Hydrolysis of a Nitrile to an Amide
A combination of mechanism-guided experimentation and kinetic modeling was used to optimise a reaction and eliminate the major reaction impurity. The model was then used to check process robustness on a 90 kg scale.
2014-Jul-16

Guest: Chris Mitchell, Takeda: Development of a modeling-based strategy for the safe and effective scale-up of highly energetic hydrogenation reactions
Development of DynoChem model to take into consideration kinetics, reactor heat transfer capabilities and gas-liquid mass transfer for scale-up of highly energetic hydrogenation reactions
2014-Jul-16

Guest: Andrew Cosbie, Amgen: Building Value into Process Understanding and Engineering Assessments
How Amgen uses process schemes as a living document to communicate among engineers, scientists, management and CMOs; to capture key process parameters, rates, ranges and references; to facilitate engineering assessments and risk assessments
2014-Jul-16

Model Driven Process Design and Development for a Continuous Process
Case study where kinetic models were used to drive process development of a continuous amination
reaction. Kinetic model was first used to optimize the process by minimizing impurity.
Then, to compare PFR and CSTRs wrt process upsets/ disturbances, RTD.
2014-Jul-14

Guest: Flavien Susanne, Novartis: Application of QbD in Continuous Processing: Approach Supported by DynoChem Process Simulation
A methodology based on process simulation using DynoChem was used to develop three consecutive continuous transformations, transfer them to kilogram scale facilities and generate the design space based on the QbD ICH Q8 guidelines
2014-Jun-18

Applicability evaluation of AspenONE and DynoChem for solubility modeling in the pharmaceutical industry
The goal was to select the most appropriate models for prediction of gas-liquid, liquid-liquid and solid-liquid solubilities and to compare the obtained data with experimental data in order to determine the most suitable model for a specific system.
2014-Jun-10

Application of In Situ Raman Spectroscopy To Facilitate Use of Hydrogen Peroxide on Kilogram Scale
The safe implementation of a hydrogen-peroxide-mediated oxidation of a poorly reactive sulfide to the corresponding sulfone is described.
2014-Jun-09

Guest: Franjo Jovic, Pliva: Modelling based approach to process development for the API synthesis hydrogenation step
Franjo Jovic of Pliva presents the design space for an API hydrogenation reaction step defined using DynoChem and model predictions verified with experimental results.
2014-May-21

Guest: Bernhard Berger, Siegfried AG: Applications of DynoChem in Thermal Process Safety – Optimization of Accumulation and Time to Maximum Rate
Working with a highly exothermic oxidation reaction, it is shown how a DC model for heat flow / Qr can be created from a few RC1 experiments, to evaluate a parameter space and assure thermal process safety
2014-Mar-20

Predicting 24 and 8 h Adiabatic Decomposition Temperature for Low Temperature Reactions by Kinetic Fitting of Nonisothermal Heat Data from Reaction Calorimeter (RC1e)
A new approach to determine the adiabatic decomposition temperature is presented here, using a combination of nonisothermal heat data and DynoChem kinetic modeling for the low temperature decomposition of a lithiated halogenated aromatic intermediate.
2014-Jan-10

Use of Modeling and Process Analytical Technologies in the Design of a Catalytic Amination Reaction: Understanding Oxygen Sensitivity at the Lab and Manufacturing Scales
An experimental mechanistic study was undertaken to understand the effect of oxygen on the reaction. A reactor model was then used to control dissolved oxygen levels on scale.
2013-Nov-28

Selected highlights at AIChE Annual Meeting 2013
List of sessions and papers at AIChE 2013 that feature DynoChem and Scale-up Systems. Including Amgen, BMS, Lilly, Nalas Engineering, Pfizer, UCD.
2013-Nov-21

Guest: Andrew Derrick, Pfizer: DynoChem applications in a busy commercial plant
Applications: Scale-up of laboratory heat flow data to pilot and production scale to assist validation based on maximum temperature Assumptions: well mixed phases, dosing controlled reaction
2013-Nov-21

Late Phase Solubility: an Advanced Automated Workflow to Support Crystallization Development
Review of the value of solubility data in late phase chemical development, development of an automated workflow to generate the data, parameter estimation and use of the solubility curves in DynoChem.
2013-Sep-27

Guest: Shane Grosser, Merck: Application of DynoChem in Process Development and Commercialization
Shane Grosser of Merck shows how they integrated DynoChem into their process development culture, making models easy to use by hundreds of users on a regular basis.
2013-Sep-25

Guest: Ed Delaney, Reaction Science: Application of DynoChem in CMC Regulatory Support
Ed shows how DynoChem kinetic models can be used to address concerns related to control of genotoxic impurities (for example sulfonate ester) in Pharmaceutical APIs
2013-Sep-25

Modeling-based Development of an Enantioselective Hydrogenation Reaction of a Sitagliptine Intermediate
This work presents a quality by design (QbD) driven approach to experiments and DynoChem modeling that was effective in obtaining enhanced process knowledge and defining a design space.
2013-Sep-09

Guest: Dan Hallow, BMS: Application of DynoChem Reaction Modeling to Quality by Design
Dan Hallow of BMS describes how DynoChem was used in a QbD approach for commercialization of an API step, especially to control formation of a critical impurity.
2013-Aug-14

Mechanisms of the Thermal and Catalytic Redistributions, Oligomerizations, and Polymerizations of Linear Diborazanes
Linear diborazanes R3N–BH2–NR2–BH3 (R = alkyl or H) are often implicated as key intermediates in the dehydrocoupling/dehydrogenation of amine-boranes to form oligo- and polyaminoboranes.
2013-Aug-13

Model-Based Scale-up and Design Space Determination for a Batch Reactive Distillation with a Dean–Stark Trap
A detailed model of a reactive distillation was developed with water removed via a Dean-Stark trap (liquid-liquid separator) for calculation of Design Space (QbD). Common cause variability and model parameter uncertainty were also accounted for.
2013-Jul-22

Enquiry based learning in chemical engineering curriculum supported by computer aided delivery
Traditional curriculum delivery in higher education has long been considered ineffective in promoting deep learning. Enquiry based learning (EBL) provides an opportunity to develop important professional attributes within the subject-specific content.
2013-Jul-08

Introduction of CAPE into an active pharmaceuticals ingredients company
Describes the process, experiences and results at ChemAgis with the training of R&D and Pilot Department professional staff in the use of CAPE software, including DynoChem.
2013-Feb-21

Optimization of the Manufacturing Route to PF-610355 ( 1 ): Synthesis of Intermediate 5
Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled β-2 adrenoreceptor agonist PF-610355. Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed.
2013-Feb-05

Optimization of the Manufacturing Route to PF-610355 ( 2 ): Synthesis of the API
PF-610355 is a novel inhaled β-2 adrenoreceptor agonist. Process development of the final intermediate and the API are discussed with emphasis on the control of physical properties and subsequent isolations.
2013-Feb-05

Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate 5
Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled β-2 adrenoreceptor agonist PF-610355. Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed.
2013-Feb-05

Optimization of the Manufacturing Route to PF-610355 (2): Synthesis of the API
PF-610355 is a novel inhaled β-2 adrenoreceptor agonist. Process development of the final intermediate and the API are discussed with emphasis on the control of physical properties and subsequent isolations.
2013-Feb-05

Selection of an Enantioselective Process for the Preparation of a CGRP Receptor Inhibitor
Two routes to the chiral indazolyl amino ester subunit were developed - either a Rh-catalyzed asymmetric hydrogenation or a biocatalytic process to install the single chiral center. The advantages and disadvantages of each process route are discussed.
2012-Dec-21

Selected highlights at AIChE Annual Meeting 2012
List of sessions and papers at AIChE 2012 that feature DynoChem and Scale-up Systems. Including BMS, Lilly, Nalas Engineering, Scale-up Systems.
2012-Oct-24

Mechanism of Metal-Free Hydrogen Transfer between Amine−Boranes and Aminoboranes
The kinetics of the metal-free hydrogen transfer from amine–borane Me2NH•BH3 to aminoborane iPr2N═BH2, yielding iPr2NH•BH3 and cyclodiborazane [Me2N-BH2]2 via transient Me2N═BH2, have been investigated in detail
2012-Sep-27

Implementing Quality by Design in Pharmaceutical Salt Selection: A Modeling Approach to Understanding Disproportionation
A mechanistic model based on thermodynamics was built to predict disproportionation.
2012-Aug-24

Development of a Process for the Preparation of Chloromethyl Chlorosulfate
A new and efficient synthesis of chloromethyl chlorosulfate (CMCS) from chloroiodomethane and chlorosulfonic acid is described.
2012-Aug-24

Intermolecular Alkyne Hydroacylation. Mechanistic Insight from the Isolation of the Vinyl Intermediate That Precedes Reductive Elimination
The isolation of the branched alkenyl intermediate that directly precedes reductive elimination of the final α,β-unsaturated ketone product is reported for the hydroacylation reaction between two alkyne.
2012-Jul-26

Drying Process Optimization for an API Solvate Using Heat Transfer Model of an Agitated Filter Dryer
Paper from Abbott, using modified Schlunder model to optimize drying conditions
2012-Jun-29

Computer aided delivery of case-based learning activities in EBL within chemical engineering curriculum
Enquiry Based Learning (EBL) in chemical engineering education provides an opportunity to develop important professional attributes of innovative problem solving, team work, initiative and communication skills within the subject-specific content.
2012-Jun-22

Enquiry-based Learning in Engineering Curriculum: are we preparing graduates ready to face future challenges?
The School initiated a substantial curriculum redesign leading to introduction of an Enquiry Based Learning approach via industrially relevant case studies throughout the curriculum, using industry standard software packages (DynoChem and HYSYS).
2012-Jun-19

ReactNMR and ReactIR as Reaction Monitoring and Mechanistic Elucidation tools
ReactNMR and ReactIR as Reaction Monitoring and Mechanistic Elucidation tools
2012-Apr-11

Modeling-Based Approach Towards Quality by Design (QbD) for the Ibipinabant API Step
Modeling-Based Approach Towards Quality by Design (QbD) for the Ibipinabant API Step
2012-Apr-11

Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor
Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor
2012-Apr-11

Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin
Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin
2012-Apr-11

Modeling, Screening and PAT: The Development of a Pharmaceutical Crystallization
Modeling, Screening and PAT: The Development of a Pharmaceutical Crystallization
2012-Apr-04

Kinetic Understanding Using NMR Reaction Profiling
Kinetic Understanding Using NMR Reaction Profiling
2012-Apr-04

Lean Filtration: Approaches for the Estimation of Cake Properties
Lean Filtration: Approaches for the Estimation of Cake Properties
2012-Apr-04

Understanding and Control of Dimethyl Sulfate in a Manufacturing Process: Kinetic Modeling of a Fischer Esterification Catalyzed by H2SO4
Understanding and Control of Dimethyl Sulfate (sulfonate ester formation) in a Manufacturing Process: Kinetic Modeling of a Fischer Esterification Catalyzed by H2SO4. Control of genotoxic impurities.
2012-Apr-04

Safe, Convenient ortho-Claisen Thermal Rearrangement Using a Flow Reactor
Presents a process that utilized a tube reactor to make 80 g of an early phase intermediate in a short time while mitigating the potential chemistry hazards. Continuous. PFR.
2012-Apr-04

Guest: Wilfried Hoffmann, Pfizer: Use of DynoChem in Process Developmentt
Presentation of how DynoChem has been used in process development at Pfizer
2012-Feb-07

Development of a Generic Mechanism for the Dehydrocoupling of Amine-Boranes: A Stoichiometric, Catalytic, and Kinetic Study of H3B·NMe2H Using the [Rh(PCy3)2]+ Fragment
The multistage Rh-catalyzed dehydrocoupling of the secondary amine-borane H3B•NMe2H, to give the cyclic amino-borane [H2BNMe2]2, has been explored using catalysts based upon cationic [Rh(PCy3)2]+ (Cy = cyclo-C6H11)
2012-Jan-19

Kinetic Modeling and Optimization of Operating Parameters for Transvinylation of Lauric Acid
The kinetic parameters and the thermodynamic parameters of the transvinylation of lauric acid were estimated using DynoChem. The optimum operating parameters were then predicted using the model and verified by performing the corresponding experiments.
2012-Jan-04

ReactNMR and ReactIR as Reaction Monitoring and Mechanistic Elucidation Tools: The NCS Mediated Cascade Reaction of α-Thioamides to α-Thio-β-chloroacrylamides
On-flow ReactIR and 1H NMR reaction monitoring, coupled with in situ intermediate characterization, was used to aid in the mechanistic elucidation of the N-chlorosuccinimide mediated transformation of an α-thioamide.
2011-Oct-26

Selected highlights at AIChE Annual Meeting 2011
AIChE 2011 Annual Meeting: Papers by and of interest to DynoChem users
2011-Oct-11

Discovery of a Novel, Efficient, and Scalable Route to Bendamustine Hydrochloride: The API in Treanda
Process Research and Development activities leading to a new and efficient route to bendamustine hydrochloride, the active ingredient in Treanda, a treatment for blood cancers, are disclosed.
2011-Aug-13

Model-Guided Design Space Development for a Drug Substance Manufacturing Process
Model-Guided Design Space Development for a Drug Substance Manufacturing Process
2011-Jul-26

Guest: Flavien Susanne, Pfizer: Development of a Continuous Crystallisation using DynoChem modelling
Crystallization Process Improvement Driven by DynoChem Process Modeling
2011-Jul-14

America’s Top Modelers: Pharmaceutical Manufacturing
America’s Top Modelers: Accelerating Pharma Process Development in Pharmaceutical Manufacturing
2011-Jun-01

A Data Driven Model Based Approach to Scale up of Hydrogenation Reactions in the API Industry
A Data Driven Model Based Approach to Scale up of Hydrogenation Reactions in the API Industry
2011-May-30

Applications in Kilo Lab Flow Chemistry and Scale-up
Includes examples of modeling reactions in a PFR and centrifugation.
2011-May-30

Scaling Up and Plant-to-Plant Transfer of Safety Data for an Exothermic Reaction
Scaling Up and Plant-to-Plant Transfer of Safety Data for an Exothermic Reaction. Calorimetry. Gas evolution. Qr. Rc1, ARC.
2011-May-30

Modeling Solid-Liquid Separations: Fine-tuning the Filtration Model
Modeling Solid-Liquid Separations: Fine-tuning the Filtration Model
2011-May-30

Kinetics of a SnAr Reaction
Kinetics of a SnAr Reaction
2011-May-30

Process Model = Process Understanding?
Process Model = Process Understanding?
2011-May-30

Marcello Bosco, Roche, Basel: Vessel Characterization and Reaction Modelling with DynoChem (Voted best presentation at European User Group Meeting)
Thermal Scale-up – Vessel Characterization and Reaction Modelling with DynoChem
2011-May-30

Models, Mass Balance, and Analytical Data
Models, Mass Balance, and Analytical Data
2011-May-30

Reaction Kinetics as a tool to underpin Control Strategy
Reaction Kinetics as a tool to underpin Control Strategy
2011-May-30

Abstracts and Program for DynoChem User Meeting London
Abstracts and Program for DynoChem User Meeting London
2011-May-18

America’s Top Modelers: PharmaQbD site
America’s Top Modelers: Accelerating Pharma Process Development on PharmaQbD site
2011-May-13

DynoChem Modeling for API Process Development: Early Stage Linking of Laboratory to At-Scale Performance
DynoChem Modeling for API Process Development: Early Stage Linking of Laboratory to At-Scale Performance
2011-May-11

Will Trieu, Amgen: Applications of the Simple Filtration and Centrifugation Tool
Applications of the Simple Filtration and Centrifugation Tool
2011-May-11

Rahn McKeown, GSK: Using DynoChem to Inform Experimental Design of Batch Crystallization: Case Studies in Scoping, Optimization, and Robustness
Using DynoChem to Inform Experimental Design of Batch Crystallization: Case Studies in Scoping, Optimization, and Robustness
2011-May-11

Modelling Small Molecule Synergistic Solubility Behavior
Modelling Small Molecule Synergistic Solubility Behavior using Regressed UNIFAC in Dynochem vs NRTL-SAC for solubility prediction and solvent selection.
2011-May-11

Pilot Scale Design and Continuous Manufacture of Novel Explosives Using Kinetic Modelling
Pilot Scale Design and Continuous Manufacture of Novel Explosives Using Kinetic Modelling
2011-May-11

Abstracts and Program for DynoChem User Meeting Chicago
Abstracts and Program for DynoChem User Meeting Chicago
2011-May-10

Development of Kinetic Model and Process Prediction
Development of Kinetic Model and Process Prediction
2011-Apr-28

Scale Up Perspectives in Pharmaceutical Industry
Scale Up Perspectives in Pharmaceutical Industry
2011-Apr-28

Kinetic Model Development for Reversible Reactions
Kinetic Model Development for Reversible Reactions
2011-Apr-28

Accelerate Process Development and Scale-up using Process Modeling
Accelerate Process Development and Scale-up using Process Modeling
2011-Apr-28

Abstracts and Program for DynoChem User Meeting Mumbai
Abstracts and Program for DynoChem User Meeting Mumbai
2011-Apr-27

Genotoxic Impurities: Strategies for Identification and Control
Modeling of reactions that can produce genotoxic impurities; comparison of model results with experimental data. Using the model to indicate the risk associated with using certain reagents. Work completed in PQRI collaborative project.
2011-Mar-29

An Example of Utilizing Mechanistic and Empirical Modeling in Quality by Design
An Example of Utilizing Mechanistic and Empirical Modeling in Quality by Design
2010-Nov-19

A Mechanistic Insight into a Simple C−N Bond Formation via SN2 Displacement: A Synergistic Kinetics and Design of Experiment (DoE) Approach
A Mechanistic Insight into a Simple C−N Bond Formation via SN2 Displacement: A Synergistic Kinetics and Design of Experiment Approach
2010-Oct-04

Selected highlights at AIChE Annual Meeting 2010
AIChE 2010 Annual Meeting: Papers by and of interest to DynoChem users
2010-Sep-15

A Detailed Study of Sulfonate Ester Formation and Solvolysis Reaction Rates and Application toward Establishing Sulfonate Ester Control in Pharmaceutical Manufacturing Processes
A Detailed Study of Sulfonate Ester Formation and Solvolysis Reaction Rates and Application toward Establishing Sulfonate Ester Control in Pharmaceutical Manufacturing Processes. From PQRI project on genotoxic impurities.
2010-Mar-31

Efficient Synthesis of 8-Oxa-3-aza-bicyclo[3.2.1]octane Hydrochloride
Efficient Synthesis of 8-Oxa-3-aza-bicyclo[3.2.1]octane Hydrochloride
2010-Feb-28

Up-front Thinking to Design a Better Lab Scale DoE
David Place and colleagues discuss use of a basic kinetic model to help design a more informative and valuable set of experiments.
2009-Nov-01

Use of Mechanistic Models to Develop Design Spaces for Drug Substance Production
Peter Clark of Scale-up Systems discussed the use of mechanistic models with explanations and examples selected for pharmaceutical scientists.
2009-Nov-01

QbD Approach to Crystallization Process Design using Process Modeling
Peter Clark of Scale-up Systems discusses opportunities for applying quality by design to crystallization processes.
2009-Oct-01

Selected highlights at ACT, AAPS and AIChE Annual Meeting 2009
Featuring links to presentations in the public domain by Abbott, BMS, Lilly, GSK, Merck, Pfizer and Wyeth.
2009-Sep-01

Feasibility study for a passive trip system to prevent a runaway reaction in a batch reactor
Feasibility study for a passive trip system to prevent a runaway reaction in a batch reactor
2009-Aug-31

Quality by design (QbD) for drug substance scale-up
Presentation by Joe Hannon describing opportunities for QbD in chemical process development, with a GSK process as central case study and discussion of model uncertainty.
2009-Jul-01

Highly efficient asymmetric synthesis of Sitagliptin
A highly efficient synthesis of sitagliptin, a potent and selective DPP-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM), has been developed.
2009-Jun-01

All abstracts: DynoChem User Group Meeting 2009
Abstracts from presentations from companies including Abbott, Amgen, AstraZeneca, Chemagis, GSK, Lilly, Merck, Pfizer, covering a range of topics from new model development to specific unit operations.
2009-May-01

All distributable presentations: DynoChem User Group Meeting 2009
Including Abbott, Amgen, AstraZeneca, Chemagis, GSK, Lilly, Merck, Pfizer, Wyeth
2009-May-01

Practical Insight on New Model Development: Filtration and Centrifugation
Presentation illustrating the steps involved in creating a model for a new unit operation, collaborating with the Scale-up Systems user support team.
2009-May-01

DynoChem Applications in Abbott's Process Safety Laboratory
DynoChem Applications in Abbott's Process Safety Laboratory. Calorimetry. ARC, Rc1, Qr, Hydrogenation, UA.
2009-May-01

Practical aspects of distillation modeling in DynoChem
Review of several applications of Dynochem tools to distillation, including avoiding unintended crystallization during distillation.
2009-May-01

Why Study a Synthetically Useless Reaction? - Unravelling Sulphonate Ester Formation using DynoChem
Review of lab and modeling work carried out in a PQRI project to establish the kinetics of sulphonate ester formation. Includes interesting and useful remarks on the 'wheel of life' of a Dynochem project.
2009-May-01

Optimization and Scale Up of chemical reaction during an API project development
Reviews application of a combination of experiments and modeling to ensure successful scale-up.
2009-May-01

An Example from GSK's Design for Manufacture Initiative: Use of Dynochem in Conjunction with Lab and Pilot Scale Data to Advance Process Understanding
DynoChem was used to develop a kinetic model for the main and side reactions using mechanistic understanding and lab/pilot scale data and to establish a suitable mechanism for the reaction to enable troubleshooting throughout lifecycle management.
2009-May-01

Pilot Plant Unit Operations Modeling as a Process Scale Tool
Mixing calculations were performed to estimate mass transfer effects for a fit-for-purpose heterogeneous reaction. Lab scale calorimetry data was scaled-up to determine required addition rates. These rates were implemented and resulted in success.
2009-May-01

Roles of mechanistic and empirical modeling / DOE in achieving Quality by Design
Mechanistic models can enhance DoE models, either indirectly or directly by inclusion in the DoE by numerical response. Response models have the potential to be used to generate the
design space predictively - “dynamic design space”.
2009-May-01

Using DynoChem to Scale Up Data from Various Calorimeters
Data from various calorimeters can be used to develop kinetic models. Potential pitfalls exist when stretching and scaling calorimetry data – obtain thermokinetic models if possible. Carefully plan lab experiments to get the most appropriate data.
2009-May-01

Development of a high performance, company specific DynoChem front-end
Developing company-specific DynoChem front-ends will take time for validation and troubleshooting. Once in place, front-ends can significantly reduce time required for model development. Includes results of modeling survey.
2009-May-01

How Process Safety and Environmental lab can guide Process Development
Merck Environmental and Process Safety lab organization. Integration of Environment and Safety to Process Development. Three examples of how Environment and Process Safety can guide process development.
2009-May-01

Lean and green, the value of API process design
Products are not optimized for production when launched. There is a lack of product and process understanding; we have empirical understanding; we don’t understand the complex physicochemical relationships. There is a high failure rate. How models help.
2009-May-01

DynoChem Modelling of 3 Continuous Stirred Tank Reactors
How to Pretend to be an Engineer using
DynoChem’s User Support Group. Able to demonstrate that the model reliably predicted the results in the laboratory. Reassured the plant manager that the continuous process would provide throughput and quality.
2009-May-01

Modeling is the Easy Part! : Getting the right data and getting the data right is the challenging part!
A good understanding of the reaction concentration with external analytical methods is needed to convert in situ analytical data into concentration.
2009-May-01

Using DynoChem to determine a suitable sampling endpoint for reaction analysis in a DoE
If an adequate Kinetic model of the mechanism can be elucidated, DoE factor ranges can be investigated prior to committing time & resource. Dynochem is a powerful tool that enables the process chemist to leverage data collected from 4 “shake- down” runs.
2009-May-01

Reaction kinetics and optimization of the copper-catalyzed oxidation of ApoA-1M
This paper summarizes the development of an optimized Cu(II)-catalyzed oxidation process for the dimer formation of ApoA-1M, the protein component of an HDL mimic with potential efficacy in atherosclerotic plaque reduction.
2009-Mar-05

N,N′-Carbonyldiimidazole-Mediated Amide Coupling: Significant Rate Enhancement Achieved by Acid Catalysis with Imidazole·HCl
Over a series of 10 aromatic amines we show the rate of CDI mediated amidation to be significantly enhanced upon introduction of imidazole·HCl as a proton source for acid catalysis.
2008-Dec-05

Data-Mining and Modeling of a Centrifuge
Data-Mining and Modeling of a Centrifuge. Filtration, centrifugation, solid liquid separation.
2008-Nov-01

The Design and Scale-up of an API Crystallization: Process Understanding Supported by Modeling to Achieve Consistency
The Design and Scale-up of an API Crystallization: Process Understanding Supported by Modeling to Achieve Consistency
2008-Nov-01

An Example from GSK's Design for Manufacture Initiative: Use of Dynochem In Conjunction with Lab and Pilot Scale Data to Advance Process Understanding
An Example from GSK's Design for Manufacture Initiative: Use of Dynochem In Conjunction with Lab and Pilot Scale Data to Advance Process Understanding
2008-Nov-01

Process Modeling Based Approach towards Quality by Design for An API Synthetic Step
Process Modeling Based Approach towards Quality by Design for An API Synthetic Step
2008-Nov-01

Use of In-Line FTIR for the Kinetic Study of the Reaction and Degradation of Propylene Oxide In the Synthesis of a Pharmaceutical Intermediate
Use of In-Line FTIR for the Kinetic Study of the Reaction and Degradation of Propylene Oxide In the Synthesis of a Pharmaceutical Intermediate
2008-Nov-01

Understanding the Impact of Magnesium to Grignard Reaction Kinetic through on-Line Monitoring
Understanding the Impact of Magnesium to Grignard Reaction Kinetic through on-Line Monitoring
2008-Nov-01

Integration of PAT for the Development and Scale-up of a Hydrogenolysis Reaction
Integration of PAT for the Development and Scale-up of a Hydrogenolysis Reaction
2008-Nov-01

An Application of Reaction Engineering and Modeling In Quality by Design
An Application of Reaction Engineering and Modeling In Quality by Design
2008-Nov-01

Optimization of API Drying Via Hemi-Solvate Conversion Kinetics
Optimization of API Drying Via Hemi-Solvate Conversion Kinetics
2008-Nov-01

Quality by Design and the Role of Mechanistic Modelling
Quality by Design and the Role of Mechanistic Modelling
2008-Oct-08

A catalyzed and highly selective ester reduction in the synthesis of an N-Acylpyrrolidine: Safe design through reaction calorimetry and modeling
A catalyzed and highly selective ester reduction in the synthesis of an N-Acylpyrrolidine: Safe design through reaction calorimetry and modeling
2008-Oct-01

Process Safety Testing and Process Modeling in the PSL Using DynoChem
Process Safety Testing and Process Modeling in the PSL Using DynoChem. Calorimetry. ARC, Rc1, Qr, Hydrogenation.
2008-Oct-01

Scale-up of Safety Data using Dynochem
Scale-up of Safety Data using Dynochem. Calorimetry. Gas evolution. Qr. Rc1, Omnical, ARC.
2008-Oct-01

Overview of DynoChem for safety applications
Overview of DynoChem for safety applications
2008-Oct-01

Green chemistry using continuous distillation to cut solvent usage
Green chemistry using continuous distillation to cut solvent usage
2008-Jun-08

Modeling-Based Approach towards On-Scale Implementation of a Methanethiol-Emitting Reaction
Modeling-Based Approach towards On-Scale Implementation of a Methanethiol-Emitting Reaction
2008-Mar-08

Application of mechanistic thinking to create process understanding and support QbD in pharmaceutical process development and scale-up
Application of mechanistic thinking to create process understanding and support QbD in pharmaceutical process development and scale-up
2008-Feb-01

Application of mechanistic thinking to create process understanding and support QbD in pharmaceutical process development and scale-up
Application of mechanistic thinking to create process understanding and support QbD in pharmaceutical process development and scale-up
2008-Feb-01

Development of a scalable synthesis of GSK183390A, a PPAR alpha / gamma agonist
Development of a scalable synthesis of GSK183390A, a PPAR alpha / gamma agonist
2007-Nov-01

Application of Modeling in a Qbd Context
Application of Modeling in a Qbd Context
2007-Nov-01

Modeling Based Approach towards on-Scale Implementation of a Methanethiol Emitting Reaction
Modeling Based Approach towards on-Scale Implementation of a Methanethiol Emitting Reaction
2007-Nov-01

Potential of S88, Batchml and Other Standards in Streamlining Process Modeling
Potential of S88, Batchml and Other Standards in Streamlining Process Modeling
2007-Nov-01

Modeling challenges in process development
Modeling challenges in process development
2007-Jun-01

Optimising reaction performance in the pharmaceutical industry by monitoring with NMR
Optimising reaction performance in the pharmaceutical industry by monitoring with NMR
2007-May-01

All abstracts: DynoChem User Group Meeting 2007
Including AstraZeneca, BMS, Chemagis, Dow, GSK, Lilly, Makhteshim, Merck, Monsanto, P&G, Pfizer, Rohm and Haas
2007-May-01

All distributable presentations: DynoChem User Group Meeting 2007
Including AstraZeneca, BMS, Chemagis, Dow, GSK, J&J, Lilly, Makhteshim, Merck, Monsanto, P&G, Pfizer, Rohm and Haas
2007-May-01

Application of DynoChem to kinetics in the laboratory and pilot plant.
Application of DynoChem to kinetics in the laboratory and pilot plant.
2007-May-01

Redesign and scale-up of an API crystallisation process
Redesign and scale-up of an API crystallisation process
2007-May-01

Modeling based approach towards on-scale implementation of a methanethiol emitting reaction
Modeling based approach towards on-scale implementation of a methanethiol emitting reaction
2007-May-01

Using DynoChem to reduce batch cycle time in a gas-liquid reactor and commission a new unit.
Using DynoChem to reduce batch cycle time in a gas-liquid reactor and commission a new unit.
2007-May-01

Optimizing a multiphase reaction using DynoChem
Optimizing a multiphase reaction using DynoChem
2007-May-01

Modeling and optimizing adiabatic multiphase, multisolid reaction systems with DynoChem
Modeling and optimizing adiabatic multiphase, multisolid reaction systems with DynoChem
2007-May-01

Scale-up optimization using simulation experiments.
Scale-up optimization using simulation experiments.
2007-May-01

GSK approach to enhancing process understanding using DynoChem: reaction kinetics examples
GSK approach to enhancing process understanding using DynoChem: reaction kinetics examples
2007-May-01

A case study of data-driven and model-based scaleup approach for API process development
A case study of data-driven and model-based scaleup approach for API process development
2007-May-01

Combined Experimental and Modeling Study of a Crystallization-Induced Dynamic Resolution
Combined Experimental and Modeling Study of a Crystallization-Induced Dynamic Resolution
2007-May-01

Exploitation of Crystallisation Analysis Tools in DynoChem to Predict Scale-Up
Exploitation of Crystallisation Analysis Tools in DynoChem to Predict Scale-Up
2007-May-01

Facilitating late stage development through integrated process modeling
Facilitating late stage development through integrated process modeling
2007-May-01

Discovery and development of a novel asymmetric hydrogenation of an unprotected enamine in the synthesis of Januvia: process improvements via mechanistic insight.
Discovery and development of a novel asymmetric hydrogenation of an unprotected enamine in the synthesis of Januvia: process improvements via mechanistic insight.
2007-May-01

Scale-up from RC1 and ARC safety tests using DynoChem
Scale-up from RC1 and ARC safety tests using DynoChem. Calorimetry. Gas evolution. Qr. Rc1, Omnical, ARC.
2007-May-01

Comparative evaluation of commercial software for kinetic parameter estimation.
Comparative evaluation of commercial software for kinetic parameter estimation.
2007-May-01

DynoChem and homogeneous mixing: an example
DynoChem and homogeneous mixing: an example
2007-May-01

DynoChem case studies in the safety lab
DynoChem case studies in the safety lab. Calorimetry. ARC, Rc1, Qr, kinetics.
2007-May-01

A kinetic investigation into the removal of carbobenxyloxy group from protected amines via hydrogenolysis reaction
A kinetic investigation into the removal of carbobenxyloxy group from protected amines via hydrogenolysis reaction
2007-Apr-01

Screening Adiabatic calorimetry: Simulation phi=1 in glass test cells by increasing the concentration
Screening Adiabatic calorimetry: Simulation phi=1 in glass test cells by increasing the concentration
2006-Jul-01

Emerging Technologies Supporting Chemical Process R&D and Their Increasing Impact on Productivity in the Pharmaceutical Industry
Review of parallel experiments (DoE), reaction kinetic modelling, kinetic analysis, QbD (design space) and new technologies (e.g. continuous reactions)
2006-May-27

Does Manufacturing in the Pharmaceutical Industry Lag Far Behind Potato Chip Makers?
Does Manufacturing in the Pharmaceutical Industry Lag Far Behind Potato Chip Makers?
2005-Dec-01

Modeling and Reactor Design for a highly Exothermic Reaction System
To identify safe operating conditions, a three step kinetic rate expression is postulated. The fitted model is used to select the best reactor configuration. Validation by successfully running both glass-plant and pilot plant scale batches.
2005-Nov-01

Modeling Fouling Effects in LDPE Tubular Polymerization Reactors. 3. Computational Fluid Dynamics Analysis of a Reacting Zone
Modeling Fouling Effects in LDPE Tubular Polymerization Reactors. 3. Computational Fluid Dynamics Analysis of a Reacting Zone
2005-Feb-28

Development of an Electrical Resistance Tomography Reactor for Pharmaceutical Processes
A review of tomography systems suitable for industrial implementation and design considerations for tomographic sensors has allowed the design of an ERT sensor compatible with stringent process requirements.
2005-Feb-01

Application of Process Modelling Tools in the Scale-Up of Pharmaceutical Crystallisation Processes
Application of Process Modelling Tools in the Scale-Up of Pharmaceutical Crystallisation Processes
2004-Nov-01

Identification of New Catalysts to Promote Imidazolide Couplings and Optimisation of Reaction Conditions Using Kinetic Modelling
Identification of New Catalysts to Promote Imidazolide Couplings and Optimisation of Reaction Conditions Using Kinetic Modelling
2004-Oct-01

One-dimensional centrifugation model
A theoretical model based on Darcy's law and conservation of mass was used to describe transient filtration on a basket centrifuge for both compressible and incompressible cakes.
2004-Apr-16

The role of CAPE in the development of pharmaceutical products
The role of CAPE in the development of pharmaceutical products
2003-Dec-31

Scale-up of homogeneous and heterogeneous reaction systems based on kinetic modelling and RC1 data in DynoChem
Scale-up of homogeneous and heterogeneous reaction systems based on kinetic modelling and RC1 data in DynoChem
2003-Sep-01

FBRM-based strategies for the control of particle size in APIs
FBRM-based strategies for the control of particle size in APIs
2003-Jun-01

Modelling Drug Release from Multi-layered Compacts with Potential for Zero-order Release Kinetics
Modelling Drug Release from Multi-layered Compacts with Potential for Zero-order Release Kinetics
2003-Jun-01

Characterisation of the scalability of hydrogenation reactions
Characterisation of the scalability of hydrogenation reactions
2002-Sep-01

Dynamic Modelling for Batch Process Simulation: A Case Study and Software Tool Development
Abstract. Importance and complexity of multiphase batch processes and their rate behavior. Example batch reaction. Value of modeling and dynamic simulation. History / origin of DynoChem and the Process Scheme in Syngenta / Zeneca / ICI.
2002-Jun-01