Prediction of food effects on the absorption of BCS class III drug based on dissolution testing : The correlation of in vitro dissolution and in vivo absorption
Prediction of food effects on the absorption of BCS class III drug based on dissolution testing
- 주제(키워드) food effect , IVIVC
- 발행기관 아주대학교
- 지도교수 박영준
- 발행년도 2016
- 학위수여년월 2016. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학
- 실제URI http://www.dcollection.net/handler/ajou/000000021943
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
The purpose of this study is to simulate the impact of food intake on drug release and absorption in vivo using in vitro dissolution method in fed condition and to establish in vitro/in vivo correlation that could predict the bioavailability of drug instead of using difficult, time-consuming and expensive in vivo bioequivalence studies. The dissolution of Entecavir (BaracludeTM), model compound of BCS class Ⅲ, was studied using the basket apparatus and paddle apparatus based on a method described in USP. The dissolution media of fed condition maintained at 37.0±0.5℃. Rotation speed of 50, 75 and 100 rpm was used. For in vivo bioavailability test in fed condition, Entecavir was orally administrated with meal in the beagle dogs and assayed the blood concentration of entecavir by LC MS/MS. The previous study, absorption of BaracludeTM was altered with food intake, as evidenced by a decrease in Cmax 63%, AUC0-t of 22% and delay in Tmax. It shows that BaracludeTM was dissolved more than 75% under fed condition with paddle method at all of rotation speeds. But it shows 10.4%, 56.2% and 67.4% at rotation speed of 50, 75 and 100 rpm under fed condition with basket method. As a result of in vivo beagle dog test, oral exposal of Fast was higher than that of Slow in proportion of in vitro dissolution rate.
more목차
1. Introduction 1
2. Materials and methods 10
2.1. Materials & instruments 10
2.2. Preparation of simulated dissolution media 11
2.3. In vitro simulation dissolution method 13
2.4. High performance liquid chromatography 14
2.5. Pharmacokinetic study 16
2.6. Formulation study 17
3. Results and discussion 18
3.1. Pharmacokinetic study 18
3.2. Recovery test of entecavir in simulated gastric fluids 20
3.3. Various in vitro conditions for predicting in vivo profiles 22
3.4. Verification of dissolution method in fed state 26
3.5. Enhancement absorption for entecavir formulation 30
3.5.1. Differences of dissolution rate in Ursodeoxycholic acid content 30
3.5.2. Differences of dissolution rate in Tartaric acid content 32
3.5.3. Differences of dissolution rate in Citric acid content 34
3.5.4. In vitro simulation dissolution and in vivo pharmacokinetic study 36
4. Conclusions 38
5. References 39
국문초록 42
