Formulation and characterization of clozapine and risperidone co-entrapped spray-dried PLGA nanoparticles

Abstract

In the current study, polylactide-co-glycolide (PLGA) nanoparticles entrapping both clozapine (CLZ) and risperidone (RIS) were formulated by spray-drying using Buchi Nano Spray Dryer B-90 (Flawil, Switzerland). Parameters such as inlet temperature, spray mesh diameter, sample flow rate, spray rate and applied pressure were optimized to produce nanoparticles having desired release profile using both low- and high-molecular weight PLGA polymer. Smallest size nanoparticle of size around 248 nm could be prepared using a 4.0 μm mesh diameter with low-molecular weight polymer. The load of CLZ and RIS was 126.3 and 58.2 μg/mg of polymer particles, respectively. Entrapment efficiency of drugs in PLGA nanoparticles was 94.74% for CLZ and 93.12% for RIS. Both the drugs released continuously from the nanoparticle formulations. PLGA nanoparticles formulated using low-molecular weight polymer released around 80% of the entrapped drug over 10 days of time. Nature of drug inside polymer particles was amorphous, and there was no chemical interaction of CLZ and RIS with polymer. Polymeric nanoparticles were found to be non-toxic in nature using PC12 cell line. This nanospray drying process proved to be suitable for developing polymeric nanoformulation delivering dual drugs for the treatment of Schizophrenia.