Paliperidone palmitate depot microspheres based on biocompatible poly(alkylene succinate) polyesters as long-acting injectable formulations

Abstract

The aim of this study was to design and evaluate biodegradable microspheres for the sustained delivery of Paliperidone Palmitate (PDP) towards the treatment of schizophrenia. The PDP-loaded microspheres were based on a series of five biocompatible poly(alkylene succinate)s, namely poly(ethylene succinate) (PESu), poly(butylene succinate) (PBSu), poly(hexylene succinate) (PHSu), poly(octylene succinate) (POSu), and poly(decylene succinate) (PDeSu), which were previously synthesized via a two-stage melt polycondensation method. Results showed that the molecular weight was higher (∼30-33k g/mol) for the polyesters synthesized using diols of lower molecular weight (PESu and PBSu), and significantly decreased (∼20k g/mol) for the three polyesters prepared with diols of higher molecular weight (PHSu, POSu and PDeSu). All polymers were of semi-crystalline nature and the melting temperatures were varying from 64.2 °C to 117.8 °C. The size of the PDP-loaded microspheres ranged from 20 to 50 μm, while XRD analysis revealed an encapsulated amorphous API. In vitro release studies revealed that PDP release is controlled by melting temperature of the polyesters. A detailed modeling analysis of the release curves was made to reveal the release mechanism. Overall results prove the suitability of the prepared polyesters to develop long-acting formulations that could enhance pharmacological effectiveness of the drug.