Betamethasone Sodium Phosphate albumin microspheres의 제조와 그 용출특성에 관한 연구

Abstract

수용성 corticosteroid계 소염제인 Betamethasone Sodium Phosphate를 함유하는 albumin microspheres를 emulsion method에 의하여 제조하고 변성조건은 chemical denaturation과 heat denaturation 두 가지로 하였다. 열 변성시킨 albumin microsphere가 terephthaloyl chloride로 화학적 변성시킨 albumin microsphere보다 구형으로 성형성이 좋고 입도분포가 비교적 균일하였으며 평균입자경은 약 10μm이었다. 가열 시간 변화 및 crosslinking agent의 농도 변화에 따른 albumin microsphere중의 약물함량의 차이는 관찰되지 않았으며 albumin microsphere내로의 약물 봉입효율이 좋았다. 약물 원말이 2분 이내에 거의 100% 용출되는데 비하여 열 변성시킨 albumin microspheres로부터의 약물용출은 heating time이 길어짐에 따라 T_(100%)가 각각 10분, 20분, 90분으로 지연되었고, 화학적 변성시킨 albumin microspheres로부터의 약물용출은 albumin에 대한 terephthaloyl chloride의 비를 증가시켰을 때 T_(100%)가 각각 420분, 480분, 840분으로 지연되었다.;Albumin microspheres containing freely water soluble Betamethasone Sodium Phosphate were prepared by chemical denaturation method using terephthaloyl chloride(TP) as a crosslinking agent, and by heat denaturation method. Their shape, size distribution of albumin microspheres, drug content in albumin microspheres and in vitro release profiles were studied. The shape of albumin microspheres prepared by chemical denaturation was irregular and rough, whereas the shape of albumin microspheres prepared by heat denaturation was spherical, smooth and compact, relatively. And the size distribution was affected by the preparing conditions, the amount of crosslinking agent or heating time, of albumin microspheres. BSP powder was released completely within 2 min, whereas T_(100%) drug release from chemically denatured microspheres were 420, 480 and 840 min for BSA:TP ratio of 1:0.5, 1:1.0 and 1:1.5 respectively. And T_(100%) drug release from heat denatured microspheres were 10, 20 and 90 min for heating time of 30, 60 and 120 min respectively.