title: Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide.
abstract: Solid dispersion technique is widely used to improve the dissolution rate of drugs. Most investigators relied on the in-vitro characterization and considered the enhanced dissolution as an indication of improved bioavailability. The current study investigated the effects of binary and ternary solid dispersions of gliclazide with polyethylene glycol 6000 (PEG 6000) and/or pluronic F68 (PL F68) on the dissolution of gliclazide. The study also investigated the intestinal absorption in presence of solid dispersion components. The latter employed the in-situ rabbit intestinal perfusion technique. Preparation of binary solid dispersion with PEG 6000 or PL F68 significantly enhanced the dissolution rate compared to pure drug. The ternary solid dispersion of gliclazide with both polymers resulted in rapid drug dissolution with most drug being released in the first five minutes. The intestinal perfusion indicated the possibility of complete drug absorption from the small intestine. This, together with slow dissolution of pure drug suggested that the absorption of gliclazide is dissolution rate limited. The presence of PEG 6000 did not alter the intestinal absorption but PL F68 showed a trend of enhanced intestinal absorption of the drug. Ternary solid dispersion can thus provide rapid absorption due to rapid dissolution and potential increase in intestinal permeability.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Gamal Mohamed
authors.initials: GM
authors.lastname: El-Maghraby
authors.forename: Abdullah Hasan
authors.initials: AH
authors.lastname: Alomrani
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003106:Colon / Q000378:metabolism; D005907:Gliclazide / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010477:Perfusion; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D044366:Transition Temperature; D014867:Water / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D000277:Adjuvants, Pharmaceutic; D014867:Water; D020442:Poloxamer; D011092:Polyethylene Glycols; D005907:Gliclazide