ethyl-cellulose and repaglinide

Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR,

Topics: Acetic Anhydrides; Acetylation; Carbamates; Cellulose; Dioscorea; Drug Carriers; Drug Compounding; Drug Liberation; Factor Analysis, Statistical; Hypoglycemic Agents; Kinetics; Microspheres; Particle Size; Piperidines; Plant Extracts; Pyridines; Solutions; Starch; Thermodynamics

A floating granular delivery system consisting of calcium silicate (CS) as porous carrier; repaglinide (Rg), an oral hypoglycemic agent; and hydroxypropyl methylcellulose K4M (HPMC K4M), ethyl cellulose (EC) and carbopol 940 (CP940) as matrix forming polymers was prepared and evaluated for its gastro-retentive and controlled release properties. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, drug content (%) and in vitro drug release was studied. The transit of floating granules of optimized formulation in the gastrointestinal (GI) tract was monitored by gamma scintigraphy in albino rabbits. The optimized formulation was compared in vivo with lactose granules (RgSCLG) prepared from identical polymers with their optimized composition ratio. Repaglinide-loaded optimized formulation was orally administered to albino rabbits and blood samples collected were used to determine pharmacokinetic parameters of Rg from floating granular formulation. Results were compared with pharmacokinetic parameters of marketed tablet formulation of Rg. The optimized formulation (RgSCG4) demonstrated favorable in vitro floating and release characteristics. Prolonged gastric residence time (GRT) of over 6 hr was achieved in all subjects for calcium silicate based floating granules of Rg. The relative bioavailability of Rg-loaded floating granules increased 3.8-fold in comparison to that of its marketed capsule. The designed system, combining excellent buoyant ability and suitable drug release pattern, offered clear advantages in terms of increased bioavailability of repaglinide.

Topics: Acrylic Resins; Administration, Oral; Animals; Biological Availability; Calcium Compounds; Carbamates; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Gastrointestinal Transit; Hypoglycemic Agents; Hypromellose Derivatives; Male; Methylcellulose; Particle Size; Piperidines; Polymers; Porosity; Rabbits; Radionuclide Imaging; Silicates