An in vitro biorelevant gastrointestinal transfer (BioGIT) system for forecasting concentrations in the fasted upper small intestine: Design, implementation, and evaluation

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• 作者：Alexandros Kourentas^a ; Maria Vertzoni^a ; Nick Stavrinoudakis^a ; Alexandros Symillidis^b ; Joachim Brouwers^c ; Patrick Augustijns^c ; Christos Reppas^a ; Mira Symillides^a ; ^{simillidou@pharm.uoa.gr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BioGIT ; Gastrointestinal transfer ; Biorelevant evaluation ; Luminal concentrations ; Precipitation ; Weak bases
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：20 January 2016
• 年：2016
• 卷：82
• 期：Complete
• 页码：106-114
• 全文大小：831 K

文摘

Design an in vitro methodology for studying gastrointestinal transfer in the fasted state and implement the methodology in vitro by using a biorelevant gastrointestinal transfer system (BioGIT); evaluate the usefulness of BioGIT in predicting luminal concentrations of lipophilic weak bases in the fasted upper small intestine.

Methods

The methodology was designed after modeling existing luminal data. Its implementation in vitro was based on a three compartment setup. Reproducibility of the transfer process was evaluated under conditions where solutions and/or suspensions were present in gastric and/or duodenal compartment and by using ranitidine, dipyridamole, ketoconazole, and posaconazole as model drugs. The transfer process as well as concentrations of dipyridamole, ketoconazole and posaconazole measured in the duodenal compartment were compared with data previously collected in the upper small intestine, after administration of identical preparations/dosage forms to fasted adults.

Results

Using BioGIT, the transfer process was performed reproducibly in all cases (RSD < 12.9%); data with dipyridamole and ketoconazole were in line with luminal data in humans. Dipyridamole, ketoconazole and posaconazole concentrations in duodenal compartment were also in line with previously measured concentrations in the fasted upper small intestine of healthy adults.

Conclusions

BioGIT system could be useful for the evaluation of the impact of gastrointestinal transfer on concentrations in the upper intestinal lumen during the first hour, after oral administration of dispersing/solution dosage forms of lipophilic weak bases.