Central composite design optimization for a controlled valsartan release from polycaprolactone microspheres

• Published in: Journal of applied polymer science Vol. 139; no. 5
• Main Authors: Sadoun‐Daikha, Ounissa, González Rodríguez, María Luisa, Azouz, L' Hachemi, Rabasco, Antonio M., Rezgui, Farouk
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 05.02.2022; Wiley Subscription Services, Inc
• Subjects: biocompatibility; biodegradable; biomedical applications; Design factors; Design of experiments; Design optimization; drug delivery systems; Encapsulation; High performance liquid chromatography; Independent variables; Materials science; Microspheres; Particle size; Polycaprolactone; polyesters; Polymers; Sustained release; Thermal analysis
• ISSN: 0021-8995; 1097-4628
• DOI: 10.1002/app.51584

This investigation aimed to develop polycaprolactone (PCL) microspheres, which provide better control of valsartan release. Central composite experimental design (2‐factor, 3‐level) was used to study the effect of two independent variables, namely drug amount (X1) and organic phase volume (X2), on encapsulation efficiency (Y1) and particle size (Y2). The drug‐containing microspheres were prepared by a single emulsion solvent evaporation method and characterized by various techniques including high performance liquid chromatography, thermal analysis, X‐ray diffraction analysis, scanning electron microscopy, and particle size analysis. The optimum conditions found by the quadratic models were yielded microspheres with an encapsulation efficiency of about 79% and a particle size of 51 μm. The optimal formulation improved drug release in simulated gastric fluid for the first 2 h, while it provided a sustained release, in phosphate buffered saline (pH 6.8). The formulations prepared with a lower organic phase volume (4 ml) have reduced the burst effect and therefore provided better control of valsartan release. Mathematical modeling studies showed that the encapsulated drug release was governed by Fickian‐diffusion mechanism. Valsartan was successfully encapsulated in polycaprolactone microspheres. The application of central composite design optimization gives an optimal formulation having an EE of 79.045% and a particles size of 50.975 μm. The formulations prepared with a low organic phase volume provided a reduction of the burst release at pH 6.8. The encapsulated drug release was governed by Fickian‐diffusion mechanism.