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Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture.
Mol Pharm. 2009 Sep-Oct; 6(5):1492-505.MP

Abstract

The objective of this study was to investigate the phase behavior of amorphous solid dispersions composed of a hydrophobic drug and a hydrophilic polymer following exposure to elevated relative humidity. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC) and moisture sorption analysis were performed on five model systems (nifedipine-poly(vinylpyrrolidone) (PVP), indomethacin-PVP, ketoprofen-PVP, droperidol-PVP, and pimozide-PVP) immediately after production of the amorphous solid dispersions and following storage at room temperature and elevated relative humidity. Complete miscibility between the drug and the polymer immediately after solid dispersion formation was confirmed by the presence of specific drug-polymer interactions and a single glass transition (T(g)) event. Following storage at elevated relative humidity (75-94% RH), nifedipine-PVP, droperidol-PVP, and pimozide-PVP dispersions formed drug-rich and polymer-rich amorphous phases prior to crystallization of the drug, while indomethacin-PVP and ketoprofen-PVP dispersions did not. Drug crystallization in systems exhibiting amorphous-amorphous phase separation initiated earlier (<6 days at 94% RH) when compared to systems that remained miscible (>or=46 days at 94% RH). Evidence of moisture-induced amorphous-amorphous phase separation was observed following storage at as low as 54% RH for the pimozide-PVP system. It was concluded that, when an amorphous molecular level solid dispersion containing a hydrophobic drug and hydrophilic polymer is subjected to moisture, drug crystallization can occur via one of two routes: crystallization from the plasticized one-phase solid dispersion, or crystallization from a plasticized drug-rich amorphous phase in a two-phase solid dispersion. In the former case, the polymer is still present in the same phase as the drug, and can inhibit crystallization to a greater extent than the latter scenario, where the polymer concentration in the drug phase is reduced as a result of the amorphous-amorphous phase separation. The strength of drug-polymer interactions appears to be important in influencing the phase behavior.

Authors+Show Affiliations

Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19634917

Citation

Rumondor, Alfred C F., et al. "Phase Behavior of Poly(vinylpyrrolidone) Containing Amorphous Solid Dispersions in the Presence of Moisture." Molecular Pharmaceutics, vol. 6, no. 5, 2009, pp. 1492-505.
Rumondor AC, Marsac PJ, Stanford LA, et al. Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. Mol Pharm. 2009;6(5):1492-505.
Rumondor, A. C., Marsac, P. J., Stanford, L. A., & Taylor, L. S. (2009). Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. Molecular Pharmaceutics, 6(5), 1492-505. https://doi.org/10.1021/mp900050c
Rumondor AC, et al. Phase Behavior of Poly(vinylpyrrolidone) Containing Amorphous Solid Dispersions in the Presence of Moisture. Mol Pharm. 2009 Sep-Oct;6(5):1492-505. PubMed PMID: 19634917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. AU - Rumondor,Alfred C F, AU - Marsac,Patrick J, AU - Stanford,Lindsay A, AU - Taylor,Lynne S, PY - 2009/7/29/entrez PY - 2009/7/29/pubmed PY - 2009/12/16/medline SP - 1492 EP - 505 JF - Molecular pharmaceutics JO - Mol Pharm VL - 6 IS - 5 N2 - The objective of this study was to investigate the phase behavior of amorphous solid dispersions composed of a hydrophobic drug and a hydrophilic polymer following exposure to elevated relative humidity. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC) and moisture sorption analysis were performed on five model systems (nifedipine-poly(vinylpyrrolidone) (PVP), indomethacin-PVP, ketoprofen-PVP, droperidol-PVP, and pimozide-PVP) immediately after production of the amorphous solid dispersions and following storage at room temperature and elevated relative humidity. Complete miscibility between the drug and the polymer immediately after solid dispersion formation was confirmed by the presence of specific drug-polymer interactions and a single glass transition (T(g)) event. Following storage at elevated relative humidity (75-94% RH), nifedipine-PVP, droperidol-PVP, and pimozide-PVP dispersions formed drug-rich and polymer-rich amorphous phases prior to crystallization of the drug, while indomethacin-PVP and ketoprofen-PVP dispersions did not. Drug crystallization in systems exhibiting amorphous-amorphous phase separation initiated earlier (<6 days at 94% RH) when compared to systems that remained miscible (>or=46 days at 94% RH). Evidence of moisture-induced amorphous-amorphous phase separation was observed following storage at as low as 54% RH for the pimozide-PVP system. It was concluded that, when an amorphous molecular level solid dispersion containing a hydrophobic drug and hydrophilic polymer is subjected to moisture, drug crystallization can occur via one of two routes: crystallization from the plasticized one-phase solid dispersion, or crystallization from a plasticized drug-rich amorphous phase in a two-phase solid dispersion. In the former case, the polymer is still present in the same phase as the drug, and can inhibit crystallization to a greater extent than the latter scenario, where the polymer concentration in the drug phase is reduced as a result of the amorphous-amorphous phase separation. The strength of drug-polymer interactions appears to be important in influencing the phase behavior. SN - 1543-8384 UR - https://www.unboundmedicine.com/medline/citation/19634917/Phase_behavior_of_poly_vinylpyrrolidone__containing_amorphous_solid_dispersions_in_the_presence_of_moisture_ L2 - https://doi.org/10.1021/mp900050c DB - PRIME DP - Unbound Medicine ER -