Tags

Type your tag names separated by a space and hit enter

Thermodynamic Modeling of Solvent-Impact on Phase Separation in Amorphous Solid Dispersions during Drying.
Mol Pharm. 2020 07 06; 17(7):2721-2733.MP

Abstract

Understanding and prevention of unwanted changes of a pharmaceutical formulation during the production process is part of the critical requirements for the successful approval of a new drug product. Polymer-based formulations, so-called amorphous solid dispersions (ASDs), are often produced via solvent-based processes. In such processes, active pharmaceutical ingredients (APIs) and polymers are first dissolved in a solvent or solvent mixture, then the solvent is evaporated, for example, via spray drying or rotary evaporation. During the drying step, unwanted liquid-liquid phase separation may occur, leading to polymer-rich and API-rich regions with crystallization potential, and thus, heterogeneities and a two-phasic system in the final ASD. Phase separation in ASDs may impact their bioperformance because of the locally higher degree of API supersaturation. Although it is known that the choice of the solvent plays an important role in the formation of heterogeneities, solvent-impact on ASD drying and eventual product quality is often neglected in the process design. This study aims to investigate for the first time the phase behavior and drying process of API/polymer/solvents systems from a thermodynamic perspective. Unwanted phase changes during the drying process of the ASD containing hydroxypropyl methylcellulose acetate succinate and naproxen prepared from acetone/water or ethanol/water solvent mixtures were predicted using the thermodynamic model PC-SAFT. The predicted phase behavior and drying curves were successfully validated by confocal Raman spectroscopy.

Authors+Show Affiliations

Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Strasse 70, D-44227 Dortmund, Germany.Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Strasse 70, D-44227 Dortmund, Germany.Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Strasse 70, D-44227 Dortmund, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32463685

Citation

Dohrn, Stefanie, et al. "Thermodynamic Modeling of Solvent-Impact On Phase Separation in Amorphous Solid Dispersions During Drying." Molecular Pharmaceutics, vol. 17, no. 7, 2020, pp. 2721-2733.
Dohrn S, Reimer P, Luebbert C, et al. Thermodynamic Modeling of Solvent-Impact on Phase Separation in Amorphous Solid Dispersions during Drying. Mol Pharm. 2020;17(7):2721-2733.
Dohrn, S., Reimer, P., Luebbert, C., Lehmkemper, K., Kyeremateng, S. O., Degenhardt, M., & Sadowski, G. (2020). Thermodynamic Modeling of Solvent-Impact on Phase Separation in Amorphous Solid Dispersions during Drying. Molecular Pharmaceutics, 17(7), 2721-2733. https://doi.org/10.1021/acs.molpharmaceut.0c00418
Dohrn S, et al. Thermodynamic Modeling of Solvent-Impact On Phase Separation in Amorphous Solid Dispersions During Drying. Mol Pharm. 2020 07 6;17(7):2721-2733. PubMed PMID: 32463685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thermodynamic Modeling of Solvent-Impact on Phase Separation in Amorphous Solid Dispersions during Drying. AU - Dohrn,Stefanie, AU - Reimer,Philipp, AU - Luebbert,Christian, AU - Lehmkemper,Kristin, AU - Kyeremateng,Samuel O, AU - Degenhardt,Matthias, AU - Sadowski,Gabriele, Y1 - 2020/06/16/ PY - 2020/5/29/pubmed PY - 2021/1/14/medline PY - 2020/5/29/entrez KW - HPMCAS KW - PC-SAFT KW - amorphous solid dispersions KW - liquid−liquid phase separation KW - process design KW - solvent mixtures KW - solvent selection KW - spray drying SP - 2721 EP - 2733 JF - Molecular pharmaceutics JO - Mol Pharm VL - 17 IS - 7 N2 - Understanding and prevention of unwanted changes of a pharmaceutical formulation during the production process is part of the critical requirements for the successful approval of a new drug product. Polymer-based formulations, so-called amorphous solid dispersions (ASDs), are often produced via solvent-based processes. In such processes, active pharmaceutical ingredients (APIs) and polymers are first dissolved in a solvent or solvent mixture, then the solvent is evaporated, for example, via spray drying or rotary evaporation. During the drying step, unwanted liquid-liquid phase separation may occur, leading to polymer-rich and API-rich regions with crystallization potential, and thus, heterogeneities and a two-phasic system in the final ASD. Phase separation in ASDs may impact their bioperformance because of the locally higher degree of API supersaturation. Although it is known that the choice of the solvent plays an important role in the formation of heterogeneities, solvent-impact on ASD drying and eventual product quality is often neglected in the process design. This study aims to investigate for the first time the phase behavior and drying process of API/polymer/solvents systems from a thermodynamic perspective. Unwanted phase changes during the drying process of the ASD containing hydroxypropyl methylcellulose acetate succinate and naproxen prepared from acetone/water or ethanol/water solvent mixtures were predicted using the thermodynamic model PC-SAFT. The predicted phase behavior and drying curves were successfully validated by confocal Raman spectroscopy. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/32463685/Thermodynamic_Modeling_of_Solvent_Impact_on_Phase_Separation_in_Amorphous_Solid_Dispersions_during_Drying_ L2 - https://doi.org/10.1021/acs.molpharmaceut.0c00418 DB - PRIME DP - Unbound Medicine ER -