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Influence of humidity on the phase behavior of API/polymer formulations.
Eur J Pharm Biopharm. 2015 Aug; 94:352-62.EJ

Abstract

Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH=25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as a function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions.

Authors+Show Affiliations

TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. Electronic address: Gabriele.Sadowski@bci.tu-dortmund.de.

Pub Type(s)

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

Language

eng

PubMed ID

26117187

Citation

Prudic, Anke, et al. "Influence of Humidity On the Phase Behavior of API/polymer Formulations." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 94, 2015, pp. 352-62.
Prudic A, Ji Y, Luebbert C, et al. Influence of humidity on the phase behavior of API/polymer formulations. Eur J Pharm Biopharm. 2015;94:352-62.
Prudic, A., Ji, Y., Luebbert, C., & Sadowski, G. (2015). Influence of humidity on the phase behavior of API/polymer formulations. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 94, 352-62. https://doi.org/10.1016/j.ejpb.2015.06.009
Prudic A, et al. Influence of Humidity On the Phase Behavior of API/polymer Formulations. Eur J Pharm Biopharm. 2015;94:352-62. PubMed PMID: 26117187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of humidity on the phase behavior of API/polymer formulations. AU - Prudic,Anke, AU - Ji,Yuanhui, AU - Luebbert,Christian, AU - Sadowski,Gabriele, Y1 - 2015/06/24/ PY - 2015/04/15/received PY - 2015/06/09/revised PY - 2015/06/16/accepted PY - 2015/6/29/entrez PY - 2015/6/29/pubmed PY - 2016/4/27/medline KW - Indomethacin KW - Naproxen KW - PC-SAFT KW - Phase behavior KW - Poorly-soluble pharmaceutical KW - Relative humidity KW - Thermodynamic model KW - Water sorption SP - 352 EP - 62 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 94 N2 - Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH=25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as a function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/26117187/Influence_of_humidity_on_the_phase_behavior_of_API/polymer_formulations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(15)00269-6 DB - PRIME DP - Unbound Medicine ER -