丁基原啡因經皮貼片劑之體外皮膚穿透性研究   全文下載

In Vitro Skin Permeation of Buprenorphine Transdermal Patch

此研究目的為開發含丁基原啡因之經皮吸收配方，以改善其皮膚穿透性。以pH 1.2 至10.0 的緩衝液為水相，測量丁基原啡因的油水分配係數。在pH 6.8 的0.1 M 磷酸緩衝液中，丁基原啡因的溶解度為12.97 μg/mL。使用固定式的體外擴散試驗裝置（Franz diffusion cells）研究於不同pH 值溶媒、感壓膠與穿透促進劑下，對於丁基原啡因穿透裸鼠皮的影響。丁基原啡因的穿透參數（Jss） 會隨著穿透試驗溶媒pH 值的下降而上升，後續研究選用pH 6.8 的溶媒做為皮膚穿透試驗的條件。評估polyisobutylene （PIB）、polystyrene-block-polyisoprene-block-polystyrene （SIS） 與壓克力等感壓膠的差異。不加促進劑的條件下，使用PIB 或SIS 之感壓膠時，其對丁基原啡因之皮膚穿透性較於壓克力感壓膠佳。使用丙二醇與其它促進劑以改善丁基原啡因的皮膚穿透性，發現其穿透的促進效應依序為lauric acid > linolenic acid > menthol > oleic acid > N-methyl-2-pyrrolidone （NMP） > laurocapram > glabridin。本研究使用之丁基原啡因的間質型經皮給藥系統是由壓克力型感壓膠、丙二醇與lauric acid 所組成。此系統之Jss 為2.68 ± 0.20 μg/cm2/h，且丁基原啡因對裸鼠皮的穿透率為31.68%。

This study was aimed to develop the new transdermal formulation to improve the permeability of buprenorphine. The apparent partition coefficients of buprenorphine were measured using the buffers at pH 1.2 to 10.0 as aqueous phase. The solubility of buprenorphine was 12.97 μg/mL in the 0.1 M phosphate buffer at pH 6.8. The influences of vehicles at different pH, adhesives, and permeation enhancers on the penetration of buprenorphine through nude mouse skin were investigated using the static Franz diffusion cells. The permeation parameter Jss of buprenorphine increased along with the reduction of the pH of receptor fluid, and the vehicle at pH 6.8 was used in the following skin permeation studies. The pressure sensitive adhesives (PSA) including polyisobutylene (PIB), polystyrene-block-polyisoprene-block-polystyrene (SIS), and acrylic adhesives were evaluated. The permeability of buprenorphine was higher in the PIB or SIS adhesives than that in the acrylic adhesives under the condition without enhancer. When combined the enhancers with propylene glycol (PG) to improve the penetration of buprenorphine, the permeation-enhancing effects of enhancers were in the following order: lauric acid > linolenic acid > menthol > oleic acid > N-methyl-2-pyrrolidone (NMP) > laurocapram > glabridin. Finally, a matrix-type transdermal delivery system for buprenorphine was formulated using acrylic adhesive, PG, and lauric acid. The Jss parameter was 2.68 ± 0.20 μg/cm2/h and buprenorphine permeated across the nude mouse skin was 31.68%.