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Physical stability of API/polymer-blend amorphous solid dispersions.
Eur J Pharm Biopharm. 2018 Mar; 124:147-157.EJ

Abstract

The preparation of amorphous solid dispersions (ASDs) is a well-established strategy for formulating active pharmaceutical ingredients by embedding them in excipients, usually amorphous polymers. Different polymers can be combined for designing ASDs with desired properties like an optimized dissolution behavior. One important criterion for the development of ASD compositions is the physical stability. In this work, the physical stability of API/polymer-blend ASDs was investigated by thermodynamic modeling and stability studies. Amorphous naproxen (NAP) and acetaminophen (APAP) were embedded in blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and either poly(vinylpyrrolidone) (PVP) or poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64). Parameters for modeling the API solubility in the blends and the glass-transition temperature curves of the water-free systems with Perturbed-Chain Statistical Associating Fluid Theory and Kwei equation, respectively, were correlated to experimental data. The phase behavior for standardized storage conditions (0%, 60% and 75% relative humidity (RH)) was predicted and compared to six months-long stability studies. According to modeling and experimental results, the physical stability was reduced with increasing HPMCAS content and increasing RH. This trend was observed for all investigated systems, with both APIs (NAP and APAP) and both polymer blends (PVP/HPMCAS and PVPVA64/HPMCAS). PC-SAFT and the Kwei equation turned out to be suitable tools for modeling and predicting the physical stability of the investigated API/polymer-blends ASDs.

Authors+Show Affiliations

AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany; TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany. Electronic address: samuel.kyeremateng@abbvie.com.TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraβe, D-67061 Ludwigshafen am Rhein, Germany.TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. Electronic address: gabriele.sadowski@tu-dortmund.de.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

29269154

Citation

Lehmkemper, Kristin, et al. "Physical Stability of API/polymer-blend Amorphous Solid Dispersions." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 124, 2018, pp. 147-157.
Lehmkemper K, Kyeremateng SO, Bartels M, et al. Physical stability of API/polymer-blend amorphous solid dispersions. Eur J Pharm Biopharm. 2018;124:147-157.
Lehmkemper, K., Kyeremateng, S. O., Bartels, M., Degenhardt, M., & Sadowski, G. (2018). Physical stability of API/polymer-blend amorphous solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 124, 147-157. https://doi.org/10.1016/j.ejpb.2017.12.002
Lehmkemper K, et al. Physical Stability of API/polymer-blend Amorphous Solid Dispersions. Eur J Pharm Biopharm. 2018;124:147-157. PubMed PMID: 29269154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physical stability of API/polymer-blend amorphous solid dispersions. AU - Lehmkemper,Kristin, AU - Kyeremateng,Samuel O, AU - Bartels,Mareike, AU - Degenhardt,Matthias, AU - Sadowski,Gabriele, Y1 - 2017/12/18/ PY - 2017/10/24/received PY - 2017/12/08/revised PY - 2017/12/11/accepted PY - 2017/12/23/pubmed PY - 2018/9/1/medline PY - 2017/12/23/entrez KW - Amorphous solid dispersion KW - Excipients KW - Kwei equation KW - PC-SAFT KW - Phase behavior KW - Physical stability KW - Polymer blends KW - Thermodynamic model SP - 147 EP - 157 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 124 N2 - The preparation of amorphous solid dispersions (ASDs) is a well-established strategy for formulating active pharmaceutical ingredients by embedding them in excipients, usually amorphous polymers. Different polymers can be combined for designing ASDs with desired properties like an optimized dissolution behavior. One important criterion for the development of ASD compositions is the physical stability. In this work, the physical stability of API/polymer-blend ASDs was investigated by thermodynamic modeling and stability studies. Amorphous naproxen (NAP) and acetaminophen (APAP) were embedded in blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and either poly(vinylpyrrolidone) (PVP) or poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64). Parameters for modeling the API solubility in the blends and the glass-transition temperature curves of the water-free systems with Perturbed-Chain Statistical Associating Fluid Theory and Kwei equation, respectively, were correlated to experimental data. The phase behavior for standardized storage conditions (0%, 60% and 75% relative humidity (RH)) was predicted and compared to six months-long stability studies. According to modeling and experimental results, the physical stability was reduced with increasing HPMCAS content and increasing RH. This trend was observed for all investigated systems, with both APIs (NAP and APAP) and both polymer blends (PVP/HPMCAS and PVPVA64/HPMCAS). PC-SAFT and the Kwei equation turned out to be suitable tools for modeling and predicting the physical stability of the investigated API/polymer-blends ASDs. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/29269154/Physical_stability_of_API/polymer_blend_amorphous_solid_dispersions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(17)31160-8 DB - PRIME DP - Unbound Medicine ER -