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

• Published in: The AAPS journal Vol. 16; no. 4; pp. 685 - 697
• Main Authors: Mahmoudi, Zahra N., Upadhye, Sampada B., Ferrizzi, David, Rajabi-Siahboomi, Ali R.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-07-2014
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical; Drug Compounding - methods; Drug Stability; Glipizide - chemistry; Glipizide - pharmacokinetics; Glipizide - pharmacology; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - pharmacology; Lactose - analogs & derivatives; Lactose - chemistry; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Pharmaceutical Preparations - chemistry; Pharmacology/Toxicology; Pharmacy; Polymers - chemistry; Polyvinyls - chemistry; Research Article; Solubility; polyvinyl acetate phthalate (PVAP); hypromellose (hydroxypropyl methylcellulose, HPMC); solubility enhancement; fluid bed drug layering; sugar spheres (Suglets); amorphous solid dispersions
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-014-9590-y

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.