Clopidogrel, effective for the prevention of ischemic stroke and myocardial infarction, is a poorly soluble drug with high crystallinity. In this study, the rotary evaporation method base on the solid dispersion method was used to increase the solubility of clopidogrel drug. At this time, PVP K-30 was used as a water-soluble carrier, and poloxamer was used as a surfactant. Physicochemical analysis of solid dispersions containing clopidogrel was carried out by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). It was possible to know that the solid dispersion was amorphous via SEM, DSC, and XRD. As a result of FTIR, it was confirmed that salt was formed through interaction between clopidogrel and PVP K-30 molecule. Dissolution behavior in a simulated artificial gastric juice (pH 1.2) of clopidogrel in the solid dispersions was measured using HPLC. As a result of comparing the dissolution rates with commercial Reyon clopidogrel, it was confirmed that the solid dispersion dissolution rate through rotary evaporation was higher than Reyon clopidogrel.

허혈성 뇌졸중 및 심근경색 예방에 효과적인 클로피도그렐은 높은 결정성을 갖는 난용성 약물이다. 본 연구에서는 클로피도그렐 약물의 용해도를 높이기 위해서, 고체분산법을 바탕으로 한 회전증발법을 이용하였다. 이때, PVP K-30을 수용성 담체로 사용하였고, 폴록사머는 계면활성화제로 사용하였다. 클로피도그렐을 포접하는 고체분산체의 물리화학적 분석은 SEM, DSC, XRD, FTIR로 측정하였으며, SEM, DSC, XRD를 통하여 고체분산체가 무정형임을 알 수 있었고, FTIR의 결과로 클로피도그렐과 PVP K-30분자간 상호작용을 통해 염을 형성하고 있다는것을 확인할 수 있었다. 또한 제조된 고체분산체는 인공위액(pH 1.2)에서 방출을 실험하였으며 HPLC를 통하여 측정하였다. 시판제인 클로피도그렐 황산수소염(이연제약주식회사)과 용출률을 비교한 결과 회전증발을 통한 고체분산체의 용출률이 클로피도그렐 황산수소염(이연제약주식회사)보다 크다는 것을 확인하였다.

Keywords: clopidogrel, dissolution rate, rotary evaporation, solid dispersion