We demonstrate the successful application of the state-of-the-art AstraZeneca in-house and XtalPi... more We demonstrate the successful application of the state-of-the-art AstraZeneca in-house and XtalPi cloud-based virtual polymorph screening workflows in support of stable form selection of crystallin...
Journal of Chemical Information and Modeling, Feb 28, 2022
Computational chemistry applications have become an integral part of the drug discovery workflow ... more Computational chemistry applications have become an integral part of the drug discovery workflow over the past 35 years. However, computational modeling in support of drug development has remained a relatively uncharted territory for a significant part of both academic and industrial communities. This review considers the computational modeling workflows for three key components of drug preclinical and clinical development, namely, process chemistry, analytical research and development, as well as drug product and formulation development. An overview of the computational support for each step of the respective workflows is presented. Additionally, in context of solid form design, special consideration is given to modern physics-based virtual screening methods. This covers rational approaches to polymorph, coformer, counterion, and solvent virtual screening in support of solid form selection and design.
Combining microcrystal electron diffraction (MicroED) and a cloud-based and artificial intelligen... more Combining microcrystal electron diffraction (MicroED) and a cloud-based and artificial intelligence implemented crystal structure prediction (CSP) platform to support selection of a stable solid form of remdesivir in quick time.
Cocrystals as a solid form technology for improving physicochemical properties have gained increa... more Cocrystals as a solid form technology for improving physicochemical properties have gained increasing popularity in the pharmaceutical, nutraceutical, and agrochemical industries.
One of the major concerns in modern drug discovery and development is chemical and physical stabi... more One of the major concerns in modern drug discovery and development is chemical and physical stability of small molecule pharmaceuticals. Chemical stability is crucial for compounds at all stages of pharmaceutical R&D, from early drug discovery to formulation of liquid or solid dosage forms. Physical stability is typically related to stability of the pharmaceutical solid form. QSPR models of oxidative chemical stability were built based on a large data set of electrochemical measurements. In addition a quantum chemical approach was proposed for oxidative chemical stability ranking of small organic molecules. Examples of the models application to pharmaceutical compounds will be discussed. A typical physical instability issue of solid pharmaceuticals is related to a hydrate formation during formulation or product shell life. Transformation from anhydrate to hydrate solid form can have a significant impact on product performance and may also lead to a chemical instability. A model desc...
Application of computational methods to understanding and predicting properties of analogues for ... more Application of computational methods to understanding and predicting properties of analogues for drug discovery has enjoyed a long history of success. However, the drug development space (post-cand...
We demonstrate the successful application of the state-of-the-art AstraZeneca in-house and XtalPi... more We demonstrate the successful application of the state-of-the-art AstraZeneca in-house and XtalPi cloud-based virtual polymorph screening workflows in support of stable form selection of crystallin...
Journal of Chemical Information and Modeling, Feb 28, 2022
Computational chemistry applications have become an integral part of the drug discovery workflow ... more Computational chemistry applications have become an integral part of the drug discovery workflow over the past 35 years. However, computational modeling in support of drug development has remained a relatively uncharted territory for a significant part of both academic and industrial communities. This review considers the computational modeling workflows for three key components of drug preclinical and clinical development, namely, process chemistry, analytical research and development, as well as drug product and formulation development. An overview of the computational support for each step of the respective workflows is presented. Additionally, in context of solid form design, special consideration is given to modern physics-based virtual screening methods. This covers rational approaches to polymorph, coformer, counterion, and solvent virtual screening in support of solid form selection and design.
Combining microcrystal electron diffraction (MicroED) and a cloud-based and artificial intelligen... more Combining microcrystal electron diffraction (MicroED) and a cloud-based and artificial intelligence implemented crystal structure prediction (CSP) platform to support selection of a stable solid form of remdesivir in quick time.
Cocrystals as a solid form technology for improving physicochemical properties have gained increa... more Cocrystals as a solid form technology for improving physicochemical properties have gained increasing popularity in the pharmaceutical, nutraceutical, and agrochemical industries.
One of the major concerns in modern drug discovery and development is chemical and physical stabi... more One of the major concerns in modern drug discovery and development is chemical and physical stability of small molecule pharmaceuticals. Chemical stability is crucial for compounds at all stages of pharmaceutical R&D, from early drug discovery to formulation of liquid or solid dosage forms. Physical stability is typically related to stability of the pharmaceutical solid form. QSPR models of oxidative chemical stability were built based on a large data set of electrochemical measurements. In addition a quantum chemical approach was proposed for oxidative chemical stability ranking of small organic molecules. Examples of the models application to pharmaceutical compounds will be discussed. A typical physical instability issue of solid pharmaceuticals is related to a hydrate formation during formulation or product shell life. Transformation from anhydrate to hydrate solid form can have a significant impact on product performance and may also lead to a chemical instability. A model desc...
Application of computational methods to understanding and predicting properties of analogues for ... more Application of computational methods to understanding and predicting properties of analogues for drug discovery has enjoyed a long history of success. However, the drug development space (post-cand...
Uploads