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Development of a Targeted Mucoadhesive Drug Delivery System for the Peroral Administration of lnsulin

Shehla A. Uraizee a , Andrea M. McPhillips b , Wolfgang A. Ritschel, and Adel Sakr

Industrial Pharmacy Program, College of Pharmacy, University of Cincinnati, Ohio (USA)

Present adress: BF Goodrich Co. a , Brecksville, OH (USA), Roxane Laboratories Inc. b , Columbus, OH (USA)

A mucoadhesive drug delivery system (MDDS) that targeted the release of insulin at its site of maximal absorption (ileum) was developed and tested in vivo. The proposed delivery system was coated capsules filled with mucoadhesive granules containing insulin. Carbopol 974P® (PAA), a polyacrylic acid polymer was used as the mucoadhesive and a combination of Eudragit® L100 and Eudragit ® S100 was used as the pH-dependent coating system. A Central composite design along with response surface methodology was used to optimize the coating system to obtain drug release at the pH of the ileum (6.8). Sodium deoxycholate and Bowman-Birk inhibitor were incorporated in the dosage form as absorption enhancer and enzyme inhibitor, respectively. Initial in vivo studies indicated that the capsules were retained in the stomach and, therefore, 1 mm coated tablets were used for the final in vivo study. The four formulations tested were: (A) insulin (control), (B) insulin + enzyme inhibitor + absorption enhancer, (C) insulin + PAA + enzyme inhibitor + absorption enhancer (optimum), (D) insulin + PAA. The rank order of formulations in improving the p.o. bioavailability of insulin were as follows: D > C > B > A. The results indicate that incorporation of PAA in the delivery system helped improve the peroral bioavailability of insulin.

Key words Drug targeting · Insulin, peroral administration · Mucoadhesive drug delivery systems