#53 Optimization of controlled release intramuscular formulation for antipsychotic drug

Abstract

Presented work was aimed for optimization of poly (D,L-lactide-co-glycolide) PLGA based microsphere formulation for schizophrenia which provides 15 days sustained release for antipsychotic drug. The parenteral intramuscular route is the most preferable route of administration for efficient delivery of active substances with poor bioavailability and with a narrow therapeutic index. Schizophrenia is characterized by cycles of psychosis relapse and remission which requires a long-term treatment of antipsychotics for the prevention of relapses. As per the requirement of treatment, it is desirable to maintain drug levels in systemic circulation within the therapeutic window for a longer period. Poly (D,L-lactide-co-glycolide) (PLGA) polymers microsphere is prepared to control the release profile of anti-psychotic drug in the body. Different poly (D,L-lactide-co-glycolide) (PLGA) polymers of varying molecular weight and copolymer composition provides different release profile. Among different grades of Poly (D,L-lactide-co-glycolide) (PLGA) polymer, Poly(D,L-lactide-co-glycolide) PLGA polymer (50:50) was found suitable and further optimized during optimization trials. Biodegradable poly (D,L-lactide-co-glycolide) (PLGA) microspheres were prepared by solvent extraction and evaporation method. The release profile of the active substance is monitored for a period of 15 days in-vitro. The formulation is optimized with the use of a central composite design. During optimization trials, drug-polymer ratio, drug phase: Continuous phase ratio, and stirring speed were evaluated among formulation variables and process variables. Optimized formulations were optimized based on %entrapment efficacy, particle size distribution, burst release, day 1 release, day 7 release, and day 15 release. In-vitro releases were evaluated using bottle rotating apparatus with suitable media. In conclusion, optimized poly(D,L-lactide-co-glycolide) PLGA based intramuscular microsphere is a promising approach for controlled release injectable formulation which reduced administration frequency, increase patient compliance, increased bioavailability, prolonged therapeutic effect, minimized dose-dependent side effect, and extended-release for 15 days.