Justification of Biowaiver and Dissolution Rate Specifications for Piroxicam Immediate Release Products Based on Physiologically Based Pharmacokinetic Modeling: An In-Depth Analysis

被引：26

作者：

Li, Xiaoting ^{[1
]}

Yang, Yuanhang ^{[1
]}

Zhang, Yu ^{[1
]}

Wu, Chunnuan ^{[2
]}

Jiang, Qikun ^{[1
]}

Wang, Weiping ^{[1
]}

Li, Huixin ^{[1
]}

Li, Jing ^{[3
]}

Luo, Cong ^{[1
]}

Wu, Wenying ^{[1
]}

Wang, Yingli ^{[1
]}

Zhang, Tianhong ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Wuya Coll Innovat, Dept Pharmaceut Anal, 103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China

[2] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Dept Pharm,Tianjins Clin Res Ctr Canc, Tianjin 300060, Peoples R China

[3] Shenyang Med Coll, Sch Basic Med Sci, Liaoning Key Lab Environm Pollut & Microecol, 146 Huanghe North St, Shenyang 110016, Liaoning, Peoples R China

来源：

MOLECULAR PHARMACEUTICS | 2019年 / 16卷 / 09期

关键词：

biowaiver; interspecies extrapolation; dissolution specifications; PBPK modeling; piroxicam; PARTICLE-SIZE SPECIFICATIONS; CLASSIFICATION-SYSTEM; ORAL ABSORPTION; DRUG; SIMULATION; BIOEQUIVALENCE; PERFORMANCE; PERMEABILITY; VARIABILITY; SOLUBILITY;

D O I：

10.1021/acs.molpharmaceut.9b00350

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A quantitative prediction of human pharmacokinetic (PK) profiles has become an increasing demand for the reduction of the clinical failure of drug formulations. The existing in vitro and in vivo correlation (IVIVC) methodology could achieve this goal, but the development of IVIVC for immediate release (IR) products is challenging. Herein, we report that for certain weakly acidic biopharmaceutical classification system (BCS) class II molecules (piroxicam, PIRO), physiologically based PK (PBPK) modeling could be used as a tool to quantitatively predict PK in beagle dogs and to conduct an interspecies extrapolation to humans. First, robust PBPK models were constructed in beagle dogs under both fasted and fed states. Then, a Z-factor model was integrated to assess the effect of in vitro dissolution rates on the in vivo PK performance, and the results illustrated that PIRO IR products had a much wider dissolution space than was anticipated by bioequivalence. In addition, the parameter sensitivity analysis (PSA) assay showed that good oral absorption was achieved only when the particle size was below 150 mu m. Finally, the combined PBPK models were extrapolated to humans to specify a quality control strategy; this extrapolation constituted an extension of a biowaiver for PIRO IR formulations. The results showed that the developed method can be utilized to quantitatively predict human PK, which would be meaningful for future scale-up or postapproval changes.

引用

页码：3780 / 3790

页数：11