Buccoadhesive tablets for insulin delivery: in-vitro and in-vivo studies

In the present work, insulin (6 U/kg) was formulated into bioadhesive buccal tablets using Carbopol 934, Hydroxypropyl cellulose (HPC) or Hydroxypopylmethyl cellulose (HPMC) and different absorption promoters. The effect of different ratios of HPC or HPMC to Carbopol on the rate of water uptake was studied. The axial and radial detachment force as well as the duration of adhesion of tablets to a porcine buccal tissues were also investigated. Furthermore the hypoglycemic effect of some formulations containing HPMC and Carbopol in different ratios with different additives and enhancers was studied using diabetic male beagle dogs. The rate of water uptake of tablets prepared with 3:1, 1:1 or 1:3 of HPC or HPMC: Carbopol was directly proportion to the Carbopol content of the tablet. The incorporation of enhancers (10%) to tablets prepared with HPMC: Carbopol of 1:1 ratio did not affect to a great extent the rate of tablets hydration. On the other hand, coating one side of the tablet with 50 mg of the impermeable cutina led to a significant reduction in the rate of tablets' water uptake reaching 50% to 75% in comparison with the uncoated tablets. Carbopol had the most influential effect on both mucoadhesion force and duration followed by HPMC. Tablets prepared with 100% HPC completely eroded within 6 hours during the measurement of the duration of adhesion. The incorporation of Carbopol with this polymer significantly improved its mucoadhesion duration reaching more than 24 hours with the 1:3 HPC: Carbopol. Ten percent of either sodium salicylate (NaSal) or sodium deoxycholate (NaDC) did not affect the duration of mucoadhesion of tablets prepared with 1:1 HPMC: Carbopol while 10% of Witepsol or Cacao butter and 1% of polyoxyethylene-9-lauryl ether (POELE) significantly reduced it. Tablets made using a polymer mixture of HPMC: Carbopol 934, 1:3 resulted in improved pharmacodynamic parameters producing a relative hypoglycemia (RH) of 6.72%. Furthermore, tablets made using polymer mixture of HPMC: Carbopol 934 in a ratio of 1:1 and containing 1% POELE resulted in 26% reduction in plasma glucose levels and producing 9.42% RH. Inclusion of other promoters such as 10% sodium deoxycholate or 10% sodium salicylate gave rise to RH values of 7.93 and 8.65% respectively.