Injectable In-Situ Forming Depot Based on PLGA and PLGA-PEG-PLGA for Sustained-Release of Risperidone: In Vitro Evaluation and Pharmacokinetics in Rabbits

Abstract

In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA® were compared in rabbits. Formulation containing 50% (w/w %) of PLGA-PEG-PLGA triblock revealed sustained release for about one month. Scanning electron microscopy (SEM) showed a porous structure for ISFI, while a structure with fewer pores was observed in the triblock. Cell viability in ISFG formulation in the first days was more than ISFI due to the gradual release of NMP to the release medium. Pharmacokinetic data displayed that optimal PLGA-PEG-PLGA creates a consistent serum level in vitro and in vivo through 30 days, and histopathology results revealed nearly slight to moderate pathological signs in the rabbit’s organs. The shelf life of the accelerated stability test didn’t affect the results of the release rate test and demonstrated stability in 24 months. This research confirms the better potential of the ISFG system compared with ISFI and Risperdal CONSTA®, which would increase patients’ compliance and avoid problems of further oral therapy.

Keywords

• risperidone
• PLGA
• PLGA-PEG-PLGA
• Risperdal CONSTA^®
• ISFI
• ISFG