Formulation predictive dissolution (fPD) testing to advance oral drug product development: An introduction to the US FDA funded '21st Century BA/BE' project

被引：40

作者：

Hens, Bart ^{[1
,2
]}

Sinko, Patrick D. ^{[1
]}

Job, Nicholas ^{[1
]}

Dean, Meagan ^{[1
]}

Al-Gousous, Jozef ^{[1
]}

Salehi, Niloufar ^{[3
,4
]}

Ziff, Robert M. ^{[3
,4
]}

Tsume, Yasuhiro ^{[1
]}

Bermejo, Marival ^{[1
,5
]}

Paixao, Paulo ^{[1
,6
]}

Brasseur, James G. ^{[7
,8
]}

Yu, Alex ^{[1
]}

Talattof, Arjang ^{[1
]}

Benninghoff, Gail ^{[1
]}

Langguth, Peter ^{[9
]}

Lennernas, Hans ^{[10
]}

Hasler, William L. ^{[11
]}

Marciani, Luca ^{[12
,13
,14
]}

Dickens, Joseph ^{[15
]}

Shedden, Kerby ^{[15
]}

Sun, Duxin ^{[1
]}

Amidon, Gregory E. ^{[1
]}

Amidon, Gordon L. ^{[1
]}

机构：

[1] Univ Michigan, Dept Pharmaceut Sci, Coll Pharm, Ann Arbor, MI 48109 USA

[2] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, B-3000 Leuven, Belgium

[3] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA

[5] Miguel Hernandez Univ, Dept Engn, Pharm Sect, Alicante, Spain

[6] Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Av Prof Gama Pinto, P-1649003 Lisbon, Portugal

[7] Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA

[8] Univ Colorado, Dept Aerosp Engn Sci, Boulder, CO 80309 USA

[9] Johannes Gutenberg Univ Mainz, Dept Pharmaceut Technol & Biopharmaceut, Staudinger Weg 5, D-55099 Mainz, Germany

[10] Uppsala Univ, Dept Pharm, Uppsala, Sweden

[11] Univ Michigan, Div Gastroenterol, Dept Internal Med, Ann Arbor, MI 48109 USA

[12] Nottingham Univ Hosp NHS Trust, Nottingham Digest Dis Ctr, Nottingham NG7 2UH, England

[13] Nottingham Univ Hosp NHS Trust, NIHR Nottingham Biomed Res Ctr, Nottingham NG7 2UH, England

[14] Univ Nottingham, Nottingham NG7 2UH, England

[15] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2018年 / 548卷 / 01期

关键词：

In vivo dissolution; Bioequivalence; Bioavailability; Oral absorption; MRI; Manometry; Computational fluid dynamics; IN-VIVO DISSOLUTION; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; DIFFUSION-CONTROLLED DISSOLUTION; GASTROINTESTINAL SIMULATOR GIS; DOSAGE FORMS; INDUCED VARIABILITY; VITRO DISSOLUTION; WORKSHOP REPORT; ABSORPTION; MODEL;

D O I：

10.1016/j.ijpharm.2018.06.050

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.

引用

页码：120 / 127

页数：8