Formulation of glibenclamide nanocrystals by a solvent change process. Influence of polymers on the dissolution rate.

EVA CAROLINA ARRUA; CLAUDIO J. SALOMON

Congreso; 3º Reunión Internacional de Ciencias Farmacéuticas; 2014

FORMULATION OF GLIBENCLAMIDE NANOCRYSTALS BY A SOLVENT CHANGE PROCESS. INFLUENCE OF POLYMERS ON THE DISSOLUTION RATE.Arrúa E.C.,1 Salomon C.J.1,21IQUIR-CONICET, Rosario, Argentina. 2Área Técnica Farmacéutica, Departamento Farmacia. Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 531, S2002LRK Rosario, Argentina. arruacarolina@gmail.comGlibenclamide (GB), originally described as a K+-ATP transporter blocker that interacts with sulfonylurea receptors, is a second generation sulphonylureas oral hypoglycemic agent used for the management of diabetes mellitus. Glibenclamide belong to BCS class II. Thus, its bioavailability is erratic and incomplete. Reducing the particle size of a drug to a nano-scale leads to an increased surface area-to-volume ratio, increased dissolution velocity and adhesiveness, and improved in vivo performance of poorly soluble drugs. The aim of this work was to formulate GB nanocrystals via nanoprecipitation. The influence of preparation parameters on particle size, stabilizer type and concentration, and type of drying were evaluated. For a basic formulation, GB and Eudragit RLPO were dissolved in acetone/etanol (2:1) at 25°C to form uniform organic solution. The prepared organic solution was then injected slowly dropwise with the help of a syringe into an aqueous phase, with or without PEG6000, containing a defined amount of a poloxamer derivative (P-188 or P-407) kept under high-speed agitation to get desired dispersion. The resulting dispersion was then stirred magnetically at 500 rpm at room temperature for 12 h to evaporate organic solvent. Solids were collected after filtration, washed with deionized water and dried at 40 oC or freeze drying. All samples were prepared in triplicate. The results showed that the GB crystals size and stability was dependent on the type of polymer used. Micron and sub-micron size particles were obtained by modifying the drying process. The results also showed that the dissolution of GB crystals was affected by changing the drug: polymer ratio and also the type of poloxamer. In conclusion, GB nanocrystals, consisting of pure drug and a minimum of surface active agents required for stabilization is a convenient approach to modify the drug dissolution rate.Key words: Glibenclamide, nanoprecipitation, poloxamers freeze drying.Acknowledgments: The authors express their gratitude to the National University of Rosario (U.N.R.), and The National Council Research (CONICET, Argentina). E.C.A. gives thanks to ANPCYT, Argentina for a fellowship.