Improving the drug dissolution profile of poorly aqueous soluble lovastatin using hydrophilic polymers by solid dispersion and physical mixing techniques

Abstract

Background: Improvement of the dissolution rate and solubility of poorly aqueous soluble drugs using solid dispersion (SD) techniques are considered as one of the most attractive processes. The focus of the current research project is to investigate the dissolution property of lovastatin (LVT) using SD technology comprising of drug, excipients, and carrier. Aim and Objectives: The main objective of this study is to augment the dissolution profile of LVT, a statin medication belongs to biopharmaceutics classification system Class II drugs and water-insoluble, by applying SD procedures. Materials and Methods: The melt solvent/fusion and physical mixing (PM) methods were employed to prepare the SDs. PMs of LVT and hydrophilic carriers such as Kollidon 90F and Kollicoat IR were prepared and investigated at three different ratios (1:0.5, 1:1, and 1:2). SD formulation of LVT was prepared by melt solvent or fusion technique using hydrophilic carriers and polyethylene glycol at 1:0.5:5, 1:1:5, and 1:2:5 ratios. The characterization of the prepared SD formulations was investigated by scanning electron microscopy (SEM) and in vitro dissolution studies. Results: Physical characterization experiment showed that SD of LVT prepared by fusion technique demonstrated improved dissolution property compared to the PM formulations or pure drug attributable to the conversion of LVT into an amorphous and/or less crystalline form. The results of in vitro dissolution enhancement order followed the same trend both in SD formulations and in PMs (Kollicoat IR> Kollidon 90F). The SEM analyses indicated that crystallinity of drug decreased in the SD formulation suggesting a portion of LVT could be in an amorphous state. Conclusion: The outcomes suggested a remarkably increased dissolution rate of LVT through SD systems prepared with suitable and correct proportion of polymers by melt solvent method and PM technique when compared with the pure drug dissolution profile. This was because of the hydrophilic carriers which affected the crystal structure of the drug. Hence, this approach of SD technique utilizing the above-mentioned carriers could be employed as a substantial formulation strategy to enhance the in vitro dissolution rate which, in turn, may improve the oral bioavailability of the water-insoluble drugs.