설린닥의 경구용 지속성 제제설계 및 생체이용율

• 영문명: The Formulation and Bioavailability of Oral Sustained Release Sulindac Delivery System
• 발행기관: 대한약학회
• 저자명: 이계주(Gye Ju Rhee) 박선희(Sun Hee Park) 황성주(Sung Joo Whang)
• 간행물 정보: 『약학회지』제41권 제1호 (1997년), 60~73쪽, 전체 14쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1997.01.31

영문 초록

In order to design a 24 hr sustained release preparation of sulindac for oral administration, fast release pellet (FR), slow release pellet (SR) and two combined formulation (1 : 1 and 1 : 2) were prepared. The pharmacokinetic effect of such preparations has been evaluated using rabbits as a suitable in vivo model, and tested in man. Dose determination was carried out using curve fitting according to RSTPJP II program. In bioavailability test using rabbit, AUCs of sulindac in a few designed formulations were similar to each other. Cmax- of RF and SR were 1.8 times and 1.2 times higher, respectively, compared to that of combined formulation (FR:SR=1:1). While plasma concentration of FR and SR decreased rapidly, that of combined formulation (FR:SR 1:1) lasted at the level close to Cmax for 24 hrs. Plasma concentration of sulfide form from the combined pellet(FR:SR=1:1) lasted for 24 hrs, and its AUC value was 1.4-fold, 2.7-fold. and 1.2-fold greater than FR pellet, SR pellet and combined pellet (FR:SR 1 : 2). Thus, the combined pellet of 1:1 ratio was found to be the most effective for oral sustained release formulation. Bioavailability test in human showed that AUC of sulfide from TSRP (1 : 1) was approximately 1.5 times greater than total AUC of Immbaron(R) administered twice in a day. While Tmax of sulfide from lmmbaron(R) was 4.33 +/- 1.37 hr (lst administration) and 3.33 +/- 0.82 hr (2nd administration), respectively, that of sulfide from TSRP increased to 7.17 +/- 2.86 hr. Plasma concentration of sulfide from TSRP was sustained at more, than 1.0mcg.hr/ml until 24 hrs after one dose administration. In addition, TSRP may decrease local adverse reaction in the stomach, since plasma concentration of sulfide from the combined pellet was low within 2hrs in the stomach. In conclusion, it is suggested that TSRP formulation may be effective for oral 24 hr sustained release formulation of sulindac dosing 300 ~ 350mg once a day.

키워드

Bioavailability Immbaron TSRP Sustained release pellet AUC Tmax.