| Project/Area Number |
15K18946
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Hiroshima International University |
|---|
Principal Investigator |
Tanaka Yusuke 広島国際大学, 薬学部, 助教 (10435068)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
|---|
| Keywords | 過飽和溶解 / 消化管吸収 / 難溶解性薬物 / 消化管内薬物濃度 / 過飽和 / 塩 / 溶解 |
|---|
| Outline of Final Research Achievements |
The aim of this study is to clarify the key factors to determine oral absorption of supersaturated drugs, and applying the knowledge to in vitro predictive methodology and/or physiologically based pharmacokinetic model.
In the case of study using cinnarizine, it was clarified that the re-dissolution was key process for the intestinal absorption. Also, since cinnarizine rapidly precipitated in the duodenum, different supersaturation stabilities in different doses observed in in vitro precipitation experiment was not reflected to in vivo absorption. The study using pioglitazone revealed that the absorbed amount of a supersaturated drug is determined by the balance between the absorption and precipitation rate in the GI tract, and therefore there is possibility that precipitation process may be overestimated if evaluated in a closed dissolution system.
We believe that our findings are of significance in the development of an ideal PBPK model and in vitro predictive dissolution tool.
|
