친수성고분자 및 비이온성 계면활성제를 이용한 펠로디핀 서방정제의 설계

Abstract

Felodipine, a calcium-antagonist of dihydropyridine type, is a poorly water soluble drug and has very low bioavailability. As preceding studies, use of solid dispersion systems and surfactants (solubilizers) has been suggested to increase dissolution and to improve bioavailability of felodipine. But in case of solid dispersion systems, large amount of toxic organic solvents should be used and manufacturing process time become longer than conventional process. In case of using surfactants, as time elapsed, decreasing of dissolution rate of felodipine due to crystallization has been reported. In this study, Copovidon as a hydrophilic polymer and Transcutol® as a surfactant were combined to formulations in order to increase dissolution of felodipine and conventional wet granulation process were applied to manufacturing of formulations. The effect of Copovidon and Transcutol® on the dissolution of felodipine was investigated in-vitro. When Copovidon and Transcutol® used simultaneously, the dissolution rate of felodipine was prominently increased compared with when used separately and the maximum increase in the dissolution of felodipine was 5.8 fold compared to control. This is most probably due to synergy effect by combination of Copovidon and Transcutol®. Felodipine sustained release tablets were successfully formulated using several grades of HPMC as a release retarding agent. The stability of felodipine sustained release tablet was evaluated after storage at accelerated condition (40oC/75% RH) for 6months in HDPE (High density polyethylene) bottle. Neither significant degradation nor change of dissolution rate for felodipine was observed after 6months. In conclusion, felodipine sustained release tablet was successfully formulated and dissolution of felodipine, poorly water soluble drug, was prominently increased and also stability was guaranteed by using combination system of hydrophilic polymer and surfactant.