Development Optimization, and Characterization of Solid Lipid Nanoparticles of Entacapone for Treatment of Parkinson Disease

Introduction: Entacapone is recommended for treating Parkinson's disease. Objectives: Entacapone's high lipophilicity showed limited therapeutic efficacy in therapeutic doses. Moreover, the short half-life enabled frequent dosing, which resulted in high toxicity. Hence, the current research aimed to improve the solubility of Entacapone and thereby accelerate the absorption and efficacy via Solid Lipid Nanoparticles (SLN). Materials and Methods: FTIR assessed the drug identification and compatibility. The DSC and XRD estimation confirmed the thermal nature and crystalline characteristics of the Entacapone. The solubility estimation was performed on several solid lipids and surfactants. SLN was developed using high-speed homogenization and probe sonication methods. Results: Glyceryl monostearate and Tween 20 were identified to be the best lipid and surfactant. The Box-Behnken design model was opted for the optimization of SLN, and further ANOVA was applied. The extent of lipid, surfactant, and sonication time was an independent variable. The particle size and entrapment efficiency were critical quality attributes for developing SLN. The best particle size achieved was 143.1 nm and -13 mV Zeta Potential with F9. The preferred batch F9 showed an entrapment efficiency of 88.67%. The in vitro release from SLN showed rapid release of the drug for an initial 2 hr. and later sustained release for about 24 hr. The optimized batch showed marked stability when assessed at 40ºC and 75 % RH for 3 months. Conclusion: The enormous improvement in solubility was attained via SLN, and the sustained released profile also boosted patient comfort and compliance.