3-month parenteral PLGA microsphere formulations of risperidone: Fabrication, characterization and neuropharmacological assessments

• Published in: Materials Science & Engineering C Vol. 75; pp. 1496 - 1505
• Main Authors: Chaurasia, Sundeep, Mounika, Kuchukuntla, Bakshi, Vasudha, Prasad, Vure
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2017; Elsevier BV
• Subjects: Animals; Antipsychotic activity; Antipsychotics; Assessments; Calorimetry; Controlled release; Copolymers; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Differential scanning calorimetry; Diffusion; Drug Evaluation, Preclinical; Drugs; Extrapyramidal system; Fabrication; Female; Formulations; Fourier analysis; Glycolic acid; Heat measurement; In vivo methods and tests; Infrared analysis; Infrared spectroscopy; Lactic Acid - chemistry; Lactic Acid - pharmacokinetics; Lactic Acid - pharmacology; Male; Materials science; Microspheres; Pharmacokinetic studies; Pharmacology; Photomicrographs; Physicochemical properties; Poly(lactic-co-glycolic acid); Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacokinetics; Polyglycolic Acid - pharmacology; Polylactide-co-glycolide; Porosity; Rats; Risperidone; Risperidone - chemistry; Risperidone - pharmacokinetics; Risperidone - pharmacology; Side effects; Solvent extraction; Spectrum analysis; Sustained release; Microspheres; Risperidone; Poly(lactic-co-glycolic acid); Antipsychotic activity; Pharmacokinetic studies
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2017.03.065

The study aims at formulation and characterization of three months parenteral risperidone loaded polymeric microspheres (p-RLPMs) as a sustained delivery system and established their in vitro and in vivo assessments. The p-RLPMs formulations were prepared by solvent extraction and diffusion method. The optimized p-RLPMs (batch RPLGA-1) formulation demonstrated favorable different physicochemical properties such as mean particle size (104±5.34μm), percent porosity (44.56±3.11%) and percent drug loading (38.42±2.67%). The physical state characterization, Fourier transformed infrared spectroscopy analysis showed no changes in the chemical structure of risperidone (RPD) in the batch RPLGA-1 formulation and differential scanning calorimetry study confirmed, pure RPD retained its crystallinity in the batch RPLGA-1 formulation. The SEM micrographs of the all p-RLPMs formulations revealed the irregular shapes and indentations. The GC/MS results showed that the residual organic solvent content in the batch RPLGA-1 formulation was below the limits. Pharmacokinetic parameters revealed that optimized RPLGA-1 formulation exhibited an initial burst followed by an excellent sustained release as compared to pure RPD as well as other formulations. Furthermore, in vivo studies of the batch, RPLGA-1 formulation showed an antipsychotic effect that was significantly prolonged over that of pure RPD solution for up to 72h with fewer extrapyramidal side effects. Thus, results of this study prove the suitability of using poly(lactic-co-glycolic acid) copolymer to develop sustained release p-RLPMs formulations that can tailor in vivo behavior and enhance the pharmacological effectiveness of the RPD. [Display omitted] •We have prepared p-RLPMs formulations using solvent extraction and diffusion method.•Optimized p-RLPMs showed favorable physicochemical properties.•Optimized p-RLPMs indicated irregular shapes and indentations.•Optimized p-RLPMs showed sustained release of RPD.•Optimized p-RLPMs demonstrated an antipsychotic effect with fewer EPS effects.