In vitro characterization of a novel polymeric system for preparation of amorphous solid drug dispersions.
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 (Tg) 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.
Colorcon Incorporated, 275 Ruth Road, Harleysville, Pennsylvania, 19438, USA.
Zahra N
ZN
Mahmoudi
Sampada B
SB
Upadhye
David
D
Ferrizzi
Ali R
AR
Rajabi-Siahboomi
D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005913:Glipizide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D012995:Solubility
D007004:Hypoglycemic Agents; D004364:Pharmaceutical Preparations; D011108:Polymers; D011145:Polyvinyls; C509290:hydroxypropylmethylcellulose-lactose matrix; C036125:polyvinylacetate phthalate polymer; D008747:Methylcellulose; D007785:Lactose; D005913:Glipizide