Supersaturation in human gastric fluids

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• 作者：Jan Bevernage^a ; Bart Hens^a ; Joachim Brouwers^a ; Jan Tack^b ; Pieter Annaert^a ; Patrick Augustijns^a ; ^{Patrick.Augustijns@pharm.kuleuven.be}
• 关键词：Supersaturation ; Biorelevant ; Precipitation inhibition ; Solubility ; Excipients
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2012
• 期刊代码：16_09396411
• 类别：pha
• 出版时间：May, 2012
• 卷：81
• 期：1
• 页码：184-189
• 文件大小：483 K

摘要

Purpose

The current study reports on supersaturation, precipitation and excipient mediated precipitation inhibition of five poorly soluble drugs (loviride, glibenclamide, itraconazole, danazol, and etravirine) in human and simulated gastric fluids.

Method

Upon induction of supersaturation in human gastric fluids (HGFs), simulated gastric fluid (SGF), and fasted state simulated gastric fluid (FaSSGF) using a solvent shift method, supersaturation and precipitation were assessed as a function of time. In addition, the precipitation inhibitory capacity of three polymers (Eudragit庐 E PO, HPMC-E5, and PVP K25) was investigated.

Results

Supersaturation in human gastric fluids was observed for all model compounds, but proved to be relatively unstable (fast precipitation), except for itraconazole. Only modest excipient-mediated stabilizing effects on supersaturation were observed using HPMC-E5 and Eudragit庐 E PO whereas PVP K25 exerted no effect. In contrast to SGF, the observed precipitation behavior in FaSSGF was similar to the behavior in human gastric fluids.

Conclusion

The present study demonstrates that supersaturation stability of drugs in human gastric fluids is in general inferior to supersaturation stability in intestinal fluids. As the potential for excipient mediated precipitation inhibition in gastric fluids was only limited, our data suggest that supersaturation should preferably be targeted to the intestine.