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

ARRÚA E; SALOMON C.J

Congreso; 3er. Reunión Internacional de Ciencias Farmacéiuticas; 2014

Glibenclamide (GB), originally described as a K+-ATP transporter blocker that interacts withsulfonylurea receptors, is a second generation sulphonylureas oral hypoglycemic agent used for themanagement of diabetes mellitus. Glibenclamide belong to BCS class II. Thus, its bioavailability is erraticand incomplete. Reducing the particle size of a drug to a nano-scale leads to an increased surface area-tovolumeratio, increased dissolution velocity and adhesiveness, and improved in vivo performance ofpoorly soluble drugs. The aim of this work was to formulate GB nanocrystals via nanoprecipitation. Theinfluence of preparation parameters on particle size, stabilizer type and concentration, and type of dryingwere evaluated. For a basic formulation, GB and Eudragit RLPO were dissolved in acetone/etanol (2:1) at25°C to form uniform organic solution. The prepared organic solution was then injected slowly dropwisewith the help of a syringe into an aqueous phase, with or without PEG6000, containing a defined amountof a poloxamer derivative (P-188 or P-407) kept under high-speed agitation to get desired dispersion. Theresulting dispersion was then stirred magnetically at 500 rpm at room temperature for 12 h to evaporateorganic solvent. Solids were collected after filtration, washed with deionized water and dried at 40 oC orfreeze drying. All samples were prepared in triplicate. The results showed that the GB crystals size andstability was dependent on the type of polymer used. Micron and sub-micron size particles were obtainedby modifying the drying process. The results also showed that the dissolution of GB crystals was affectedby 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 convenientapproach to modify the drug dissolution rate.