Buccal absorption of diazepam is improved when administered in bioadhesive tablets—An in vivo study in conscious Göttingen mini-pigs

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• 作者：Emil Meng-Lund^a ; Jette Jacobsen^a ; ^{jette.jacobsen@sund.ku.dk} ; Anette Mü ; llertz^a ; Erling B. Jø ; rgensen^b ; René ; Holm^a ; ^c ; ¹
• 关键词：Diazepam ; Buccal drug delivery ; Chitosan ; Mucoadhesive ; Mini-pigs ; Amorphous
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 December 2016
• 年：2016
• 卷：515
• 期：1-2
• 页码：125-131
• 全文大小：616 K
• 卷排序：515

文摘

Buccal delivery may be clinically beneficial for compounds with a high gastrointestinal and hepatic first pass metabolism or in situations where a fast systemic absorption is desired. The delivery of a crystalline low soluble compounds, e.g. diazepam, may be limited due to the low volume of saliva available to facilitate solvation in order to drive the permeation of drug through the buccal mucosa. Therefore, the present study investigated the potential benefits of administering diazepam either as an amorphous or as a crystalline form in mucoadhesive tablets to conscious Göttingen mini-pigs. Presentation of the compound in the amorphous form lead to a very fast absorption, however, the obtained bioavailability was at the same level observed following buccal administration of a commercially immediate release tablet. Addition of chitosan, as a mucoadhesive excipient, resulted in a higher absolute bioavailability compared to tablets without chitosan. The absorption rate for the chitosan-based tablets was significant slower, probably due to the slower diffusion of the compound out of the tablet. In vitro release data was able to predict the variations in tmax, but otherwise no correlation could be found between in vitro and in vivo data.