Comparative pharmacokinetics of PLGA & PCL based long acting injectable (LAI) risperidone microsphere formulations

Abstract

The objective of the study was to compare and evaluate the pharmacokinetics of biodegradable PLGA & PCL microspheres with Risperidal Consta TM for achieving the sustained delivery of Risperidone in the schizophrenia therapy. Five microsphere formulations o f risperidone were prepared by using two PLGA copolymers (50:50 and  75:25)  and  PCL  (PCL-45000 and  PCL-80000) polymer. All  the  five  novel  microsphere formulations (PLGA1-4  &  PCL)  and  Risperidal  ConstaTM    was  administered  to  male  Sprague  Dawley  rats  through subcutaneous route at different dose. PLGA & PCL formulations achieved higher exposure than Risperidal constaTM ie among PLGA based formulations ranked in the following order (PLGA1(1.6x) >   PLGA2 (1.5x) > PLGA3 (1.2x) > PLGA4 (0.9x)) whereas PCL formulati on demonstrated 1.3x higher exposure than Risperidal Consta. Simulations of multiple dosing at weekly or 15 -day regimen to predict the in vivo profile of risperidone following subcutaneous administration of PLGA1 -4 and PCL microspheres formulations and compared with marketed Risperidal ConstaTM revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Based on simulations it was observed that PLGA & PCL based formulations can be utilised to provide weekly and once in 15 day dosing regimen which could be an effective approach for sustained delivery of this molecule and a possible alternative to the currently available combination therapy. Therefore based on our study we conclude that development of novel microsphere based formulation by combining the PLGA & PCL systems to prepare long acting dosage forms with atypical antipsychotics will ensure patient compliance, reduce side effects, and improve the quality of life for patients who suffer from schizophrenia.