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In Vitro Characterization of a Novel Polymeric System for Preparation of Amorphous Solid Drug Dispersions

  • Research Article
  • Theme: Develop Enabling Technologies for Delivering Poorly Water Soluble Drugs: Current Status and Future Perspectives
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Abstract

Preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, often a single polymer may not bring about a significant enhancement in solubility or amorphous stability of a poorly water-soluble drug. This study describes application of a unique and novel binary polymeric blend in preparation of solid dispersions. The objective of this study was to investigate amorphous solid dispersions of glipizide, a BCS class II model drug, in a binary polymeric system of polyvinyl acetate phthalate (PVAP) and hypromellose (hydroxypropyl methylcellulose, HPMC). The solid dispersions were prepared using two different solvent methods: rotary evaporation (rotavap) and fluid bed drug layering on sugar spheres. The performance and physical stability of the dispersions were evaluated with non-sink dissolution testing, powder X-ray diffraction (PXRD), and modulated differential scanning calorimetry (mDSC). PXRD analysis demonstrated an amorphous state for glipizide, and mDSC showed no evidence of phase separation. Non-sink dissolution testing in pH 7.5 phosphate buffer indicated more than twofold increase in apparent solubility of the drug with PVAP–HPMC system. The glipizide solid dispersions demonstrated a high glass transition temperature (T g) and acceptable chemical and physical stability during the stability period irrespective of the manufacturing process. In conclusion, the polymeric blend of PVAP–HPMC offers a unique formulation approach for developing amorphous solid dispersions with the flexibility towards the use of these polymers in different ratios and combined quantities depending on drug properties.

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Authors and Affiliations

  1. Colorcon Incorporated, 275 Ruth Road, Harleysville, Pennsylvania, 19438, USA

    Zahra N. Mahmoudi, Sampada B. Upadhye, David Ferrizzi & Ali R. Rajabi-Siahboomi

Authors
  1. Zahra N. Mahmoudi
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  2. Sampada B. Upadhye
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  3. David Ferrizzi
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  4. Ali R. Rajabi-Siahboomi
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Corresponding author

Correspondence to Ali R. Rajabi-Siahboomi.

Additional information

Guest Editors: Ping Gao and Lawrence Yu

Zahra N. Mahmoudi and Sampada B. Upadhye contributed equally to this project.

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Mahmoudi, Z.N., Upadhye, S.B., Ferrizzi, D. et al. In Vitro Characterization of a Novel Polymeric System for Preparation of Amorphous Solid Drug Dispersions. AAPS J 16, 685–697 (2014). https://doi.org/10.1208/s12248-014-9590-y

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  • DOI: https://doi.org/10.1208/s12248-014-9590-y

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