Current Applied Polymer Science - Volume 7, Issue 1, 2024

Discontinuation and poor compliance with long-term oral medicine are major therapeutic issues in psychosis treatment. Poorer long-term outcomes may result from non-compliance as well as a higher chance of relapse. In order to sustain therapeutic drug plasma levels, co-administration of oral antipsychotics is necessary for commercially available long-acting injections of second-generation antipsychotics, as they have a lag period of approximately three weeks during the drug release process.

Poly(lactic-co-glycolic acid) (PLGA) encapsulated microspheres loaded with risperidone were fabricated in the current research for intramuscular administration. The single emulsion solvent evaporation technique was applied for the fabrication of microspheres. Risperidone microspheres were prepared using PLGA grade 75:25. Particle size, drug content and entrapment efficiency with a central composite design were the main optimization parameters for the formulation. The microspheres were characterized by different techniques, namely Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug content, entrapment efficiency, morphology, particle size, and in vitro release profiles, along with release kinetics of the risperidone microspheres, were studied.

The microspheres produced by the single emulsion solvent evaporation approach show smooth and spherical morphology, with particle size ranging from 3 μm to 6 μm, drug content of 99.7%, and entrapment efficiency of 98.2% with little burst release of 3% to 10%, providing drug release for 45 days and exhibiting zero order release kinetics and Korsmeyer-Peppas model for non-fickian drug release from the polymeric matrix. By applying the Quality by Design (QbD) approach and formulation parameters, microspheres with appropriate particle size, morphology, enhanced drug content, entrapment efficiency and desirable drug release profile for depot formulation can be obtained successfully.

The optimized microspheres, in comparison to the marketed Risperdal Consta™, show enhanced potential for a better depot formulation, which can further improve patient compliance.

Poly(lactic-co-glycolic acid) (PLGA), an FDA-approved copolymer, is widely recognized for its biocompatibility, biodegradability, and versatility in drug delivery systems. Despite its advantages, challenges, such as poor drug loading and burst release, motivate the exploration of innovative modifications. The current research aimed to modify the linear PLGA to lipoyl ester terminated star PLGA polymer to minimize initial burst release by increasing the molecular weight and fabricate risperidone-loaded microspheres.

In this study, we have presented a novel approach involving the synthesis of star PLGA through the direct melt polycondensation of PLGA with pentaerythritol, followed by conjugation with lipoic acid to form lipoyl ester terminated star PLGA. Structural confirmation was done by Fourier Transform Infrared spectroscopy (FT-IR), proton Nuclear Magnetic Resonance (¹H-NMR), and Gel Permeation Chromatography (GPC). Microspheres were fabricated from lipoyl ester terminated star PLGA and characterized for their particle size and surface morphology by Scanning Electron Microscopy (SEM) and in vitro drug release by dialysis bag method.

The results of the study have indicated successful conjugation of lipoic acid to star PLGA forming lipoyl ester terminated star PLGA, as confirmed by FT-IR, ¹H-NMR, and GPC analyses. Microspheres developed from the synthesized polymer exhibited particle sizes ranging from 4.64 μm to 11.7 μm and demonstrated sustained drug delivery, with 99.8% release over 45 d, in contrast to the plain drug that achieved complete dissolution within 3 h.

The resulting material has demonstrated unique bioresponsive and multifunctional properties, with evidence of successful synthesis provided through comprehensive characterization techniques, and suitability for the fabrication of microspheres for sustained drug delivery systems.