Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-beta-cyclodextrin.
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.
Sridevi
S
S
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India.
Chauhan
A S
AS
Chalasani
K B
KB
Jain
A K
AK
Diwan
P V
PV
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003505:Cyclodextrins; D004337:Drug Carriers; D004339:Drug Compounding; D005612:Freeze Drying; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; C479658:hydroxypropyl-alpha-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C010969:gliquidone