Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-beta-cyclodextrin.

Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-beta-cyclodextrin.
November 1, 2003
S Sridevi, AS Chauhan, KB Chalasani, AK Jain, and PV Diwan
Pharmazie
Medline Abstract
HighWire Press
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India.
The virtual insolubility of gliquidone in water results in poor wettability and dissolution characteristics, which may lead to a variation in bioavailability. To improve these characteristics of gliquidone, binary systems with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were prepared by classical methods such as physical mixing, kneading, co-evaporation and co-lyophilization. The solid state interaction between the drug and HP-beta-CD was assessed by evaluating the binary systems with X-ray diffraction, differential scanning calorimetry and IR- spectroscopy. The results establish the molecular encapsulation and amorphization of gliquidone. The phase solubility profile of gliquidone in aqueous HP-beta-CD vehicle resulted in an A(L) type curve with a stability constant of 1625 M(-1). The dissolution rate of binary systems was greater than that of pure drug and was significantly higher in the case of co-lyophilized and co-evaporated systems. Upon oral administration, [AUC]-alpha was significantly higher in case of co-lyophilized (2 times) and co-evaporated systems (1.5 times) compared to pure drug suspension while other binary systems showed only a marginal improvement. The study ascertained the utility of HP-beta-CD in enhancing the oral bioavailability of gliquidone, and points towards a strong influence of the preparation method on the physicochemical properties.
Publication Type:
Journal article
MeSH Terms:
Animals
Biological Availability
Calorimetry, Differential Scanning
Crystallography, X-Ray
Cyclodextrins*
Drug Carriers
Drug Compounding
Freeze Drying
Hypoglycemic Agents
Male
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Skin Absorption
Solubility
Spectrophotometry, Infrared
Sulfonylurea Compounds
alpha-Cyclodextrins*
beta-Cyclodextrins*
PMID: 14664337
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