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℃ 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 (L_f) and the ratio (R) of coating material to carrier material were evaluated using several parameters. A liquid loading factor L_f =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.