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.