title: In vitro evaluation and in vivo performance of lyophilized gliclazide.
abstract: Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic agent, gliclazide, by the aid of lyophilization was investigated. Mannitol, sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble excipients in the formulation. Lyophilized systems were found to exhibit extremely higher in vitro dissolution rate compared to the unprocessed drug powder. Solid state characterization of the lyophilized systems using X-ray powder diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry techniques revealed that dissolution enhancement was attributable to transformation of gliclazide from the crystalline to an amorphous state in the solid dispersion formed during the lyophilization process. The gastrointestinal absorption and hypoglycemic effect of the lyophilized gliclazide/SLS system were investigated following oral administration to Albino rabbits. Cmax and area under the plasma concentration-time curve of gliclazide (AUC0-12) after administration of the lyophilized formulations were significantly higher than those obtained after administration of the unprocessed gliclazide.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Minia University , El Minia , Egypt.
authors.forename: Heba F
authors.initials: HF
authors.lastname: Mansour
authors.forename: Usama F
authors.initials: UF
authors.lastname: Aly
mesh_terms: D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D065569:Gastrointestinal Absorption; D005907:Gliclazide / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D033362:Powder Diffraction; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions
chemical_list: D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol; D011205:Povidone; D005907:Gliclazide
keywords: Dissolution; gastrointestinal absorption; gliclazide; hypoglycemic effect; lyophilization