Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats

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• 作者：Camillo Benetti^a ; ¹ ; Lisa Flammini^a ; ¹ ; Valentina Vivo^a ; Paolo Colombo^a ; Gaia Colombo^b ; Lisa Elviri^a ; Carmelo Scarpignato^c ; Francesca Buttini^a ; Ruggero Bettini^a ; Elisabetta Barocelli^a ; Alessandra Rossi^a ; ^{alessandra.rossi@unipr.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Esomeprazole ; Immediate release ; Ex vivo permeability ; Rats ; Pharmacokinetics ; Pharmacodynamics
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 October 2016
• 年：2016
• 卷：239
• 期：Complete
• 页码：203-210
• 全文大小：787 K

文摘

The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted. The results showed an important effect of sodium carbonate and magnesium oxide on the drug release, on the ex vivo trans-mucosal transport and the stability in acid environment. In particular, the presence of sodium carbonate in esomeprazole tablet formulation provided the maximum increase of the drug in vitro transport across the mucosa. Then, the absorption and the antisecretory activity of this proton pump inhibitor orally administered in rats as immediate release tablets containing Na₂CO_3, was superior but not significantly different compared to delayed-release tablets having the same formula. In the adopted animal model, an activity of esomeprazole from immediate release alkaline formulation was seen also in presence of partial gastric absorption allowing inhibition of proton pumps reached via systemic circulation. This esomeprazole immediate release formulation could be used for the on-demand treatment of acid-related disorders such as gastro-esophageal reflux disease.