Development of a Self Micro-emulsifying Tablet of Cyclosporine- a by the Liquisolid Compact Technique

Purpose: The aim of this study was to enhance the dissolution rate of Cyclosporine A, a poorly water-soluble drug by developing a self micro-emulsifying (SME) tablet formulation by using the liquisolid compact technique. A liquisolid system is formed by converting a liquid formulation into a dry, free-flowing and compressible powder mixture with selected carrier material and coating material. This technique has industrial applications for low dose insoluble drugs. Method and Results: The solubility of Cyclosporine A (BCS ClassIIdrug), as a model drug in this study, was determined in several oils, surfactants and co-surfactants using an HPLC method. The self micro-emulsifying system of Cyclosporine A was constructed by using Maisine 35-1 and Lauroglycol FCC (1:1, w/w, oil phase), PEG-35 Castor Oil (surfactant) and PEG 400 (co-surfactant). The ratio of these components in the formulation was 20:50:30 (w/w) and optimized by a pseudo ternary phase diagram. The droplet size of the optimized liquid with drug was 32.9±0.1nm. The stability experiment results showed the model drug in the micro-emulsifying system was stable under storage at 60°C for a period of 10 days. Microcrystalline Cellulose (Avicel PH 101 and Avicel PH 102) and Magnesium Aluminometasilicate (Neusilin® S1) were selected as the carrier material and coating material respectively for preparing the liquisolid compact. The flowability and compactability of different liquid loading factors (Lf) and the ratio (R) of coating material to carrier material were evaluated using several parameters. A liquid loading factor Lf =0.67 and an R=0.6 were optimal for preparation of the liquisolid compact. The obtained powder mixture had good flowability (Hausner’s Ratio=1.243, Carr's Index=19.565) and good compactability (Hardness=5.18±0.33kp, Tensile Strength=0.47±0.03Mpa). The dissolution profiles of the self micro-emulsifying tablets were determined in three different media (Simulated Gastric Fluids (SGF) pH 1.2, Distilled Water (DI) and Simulated Intestinal Fluids (SIF) pH 6.8±0.1). The dissolution results showed that the dissolution rate of SME tablets was much higher when compared to the conventional tablets prepared by direct compression. Conclusion: In this study, the self micro-emulsifying formulation exhibited acceptable flowability and compressibility and the liquisolid tablets displayed significant improvement in dissolution profiles compared to the conventional tablets. Correspondence to Author: