In vitro and in vivo evaluation of an oral multiple-unit formulation for colonic delivery of insulin

详细信息    查看全文

• 作者：Alessandra Maroni^a ; Maria Dorly Del Curto^a ; Stefano Salmaso^b ; Lucia Zema^a ; Alice Melocchi^a ; Paolo Caliceti^b ; Andrea Gazzaniga^a ; ^{andrea.gazzaniga@unimi.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Oral drug delivery ; Colon delivery ; Pulsatile release ; Oral peptide delivery ; Insulin ; Swellable/erodible coating
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：108
• 期：Complete
• 页码：76-82
• 全文大小：1384 K

文摘

A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2 h of testing in 0.1 N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4 °C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6 h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds.