Oral delivery of insulin from enteric-coated capsules containing sodium salicylate: effect on relative hypoglycemia of diabetic beagle dogs.

The hypoglycemic effect of Eudragit S100 enteric-coated capsules containing sodium salicylate as an absorption promoter formulated with insulin in various ways: as physical mixture, by wet granulation or in suppository bases (polyethylene glycol 4000 or Witepsol W35) was studied in hyperglycemic beagle dogs. The capsules containing insulin formulated with sodium salicylate (50 mg) and prepared by either physical mixing or wet granulation using 10% polyvinyl pyrollidone gave almost the same results producing a maximum reduction in plasma glucose level (C(max)) of 81.53+/-8.21 and 79.59+/-5.75%, T(max) of 6 and 5 h, area under the curve (AUC) of 69.37+/-48.64 and 57.98+/-23.15% reduction hour (% red. h) and resulting in relative hypoglycemia (RH) of 8.73+/-6.12 and 7.29+/-2.91%, respectively. Formulation of insulin with sodium salicylate in PEG 4000 produced a lower AUC of 37.30+/-10.36% red. h and RH of 4.69+/-1.3%. While, formulation in Witepsol W35 (0.5, 1.0 and 2.0 g) that was sieved to produce particle size of 180-315 microm and filled in enteric-coated capsules showed that formulating insulin and sodium salicylate in 1 g base is the best formulation. It produced 25% reduction in plasma glucose levels of the hyperglycemic beagle dogs at T(max) of 4 h and the largest AUC of 100.10+/-25.72% red. h, resulting in the highest RH of 12.59+/-3.23%. In conclusion, 25-30% reduction in plasma glucose levels and RH of about 12.5% relative to subcutaneous injection of regular soluble insulin can be achieved by formulating insulin in Witepsol W35 (1 g) with sodium salicylate (50 mg) as an absorption promoter, reducing the resulting mass into particle size 180-315 microm, packing into hard gelatin capsules and coating with Eudragit S100.