Preparation and Characterization of Carvedilol-Loaded Poly (D, L) Lactide Nanoparticles/Microparticles as a Sustained Release System

Background: Polymeric nano and micro particles are promising delivery systems for the enhancement of the bioavailability of highly lipophilic drugs prone to first pass metabolism. Purpose: This study aims at preparing carvedilol polymeric nanoparticles and microparticles with high loading efficiency. Other objective was to study carvedilol release profile from the obtained particles at room and body temperatures. Method: Carvedilol PDLLA nanoparticles and microparticles were prepared using nano-precipitation method. PVA was used as emulsifying agent. The effect of the solvents (acetone, tetrahydrofuran, acetonitrile, ethanol and dichloromethane) and the polymer amount on the size, size distribution and morphology of the formed particles were studied using atomic force microscope (AFM). Results: Spherical polymeric particles were obtained in all solvents used. The used method is easy, rapid, reproducible, effective (high loading capacity of carvedilol) and consequently can be used as new strategy for the development of carvedilol controlled release dosage forms. The in vitro release profile of carvedilol has shown a sustained release pattern with a little rapid release rate at body temperature in comparison to that at room temperature. Conclusion: The carvedilol loaded PDLLA nanoparticles have been successfully prepared with high loading efficacy and small particle size when acetone was used as the organic solvent and 12.5 mg of PDLLA polymer was used. Microparticles obtained when dichloromethane was used. The Korsmeyer Peppas with T lag model was the best one to explain the sustained release behavior.Chapter One