Formulation deverlopment and stability studies of capsule containing cyclosporin a self-microemulsifying drug deliverys system

Abstract

Cyclosporin A is a white powder, insoluble in water but soluble in oil and organic solvent. The purpose of this study was to prepare capsules containing cyclosporin A self-microemulsifying drug delivery to improve solubility in water and provide good stability. The effect of type and quantity of oil, surfactant and co-surfactant to form self-microemulsion was investigated. Medium chain triglyceride was used as oil phase. The surfactants used were Cremophor® EL, Tween80 and Solutiol® HS 15. The cosurfactants used were propylene glycol, glycerine, polyethylene glycol400 and ethanol. Pseudoternary phase diagrams were constructed to evaluate the microemulsion existing area. From the results, it was found that the systems of Cremophor® El and Tween 80 provided the largest microemulsion area. Solutol® HS15 provided the smallest microemulsion area and the most phase are separation. Combined surfactants, Cremophor® El and Tween 80 yielded microemulsion regions similar to used single surfactant. Propylene glycol provided the highest solubility of cyclosporin A in oil. Increasing of co- solvent content the increased solubility but decreased the microemulsion area. The suitable system for incorporation into gelatin capsule was the system of oil : Cremophor® El : Tween80 at the ratio of 35:32.5:32.5 with propylene glycol and ethanol each 5% w/w of formulation. Each capsule contained cyclosporin A 25 mg and 100 mg. The droplets size after diluted in water were 69.19±1.36 and 74.69±1.71 nm respectively. Viscosity of formulation were 167±1.00 and 250±0.00 cP respectively which were suitable to be filled by liquid filling machine. The stability study at accelerated conditions for 4 months found that the content of drug were non significant difference from initial (p>0.05). However the storage condition had effect on dissolution of drug from capsule because capsule shell was intolerance to high temperature and high humidity that caused changing of capsule property leading to undissolved and unable to release drug.Formulation was absorbed onto microcrystallene cellulose to be dry powder and granule for filling into capsule. It was found that the dissolution rate of drug in dry power capsules was slower than that form of liquid preparation capsules.