Investigation of solid lipid particles containing isradipine

Abstract

The research aims to increase dissolution rate of isradipine – an antihypertensive poorly water-soluble drug - through proposing a novel type of drug delivery system in which solid dispersion base is incorporated to form solid lipid particles (SD-SLs). Solid dispersion was formed by melting method. Ultrasonication was used to obtained micro-sized solid lipid particles. Samples were prepared by two methods which included and excluded the solidified step in solid dispersion formation. Different drug to polymer ratios were also studied in order to optimize the formulations. The dissolution tests were perform according to USP basket method in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8). The mechanism of dissolution enhancement was determined by investigations of crystalline structure, molecular interactions, and particle size. The enhancement of drug release was depended on preparation method and appropriate polymer content in the solid dispersion bases. The drug release from SD-SLs significantly increase in comparison with drug release from solid dispersion or solid lipid particles alone. The instrumental analyses indicated the reduction of crystallinity and particle size without any chemical interactions. This combined method of solid dispersion and solid lipid particles may provide a new strategy to enhance the dissolution rate of IDP and further improve its bioavailability for treatment.