The
hypoglycemic effect of oral
insulin capsules coated with pH-dependent
Eudragit S100 and containing various absorption promoters was studied in hyperglycemic beagle dogs. The absorption enhancers used were bioadhesive
polymers,
sodium salicylate, and non-ionic
surfactants. A comparative study of the bioadhesive
polymers,
polycarbophil (PC),
hydroxypropyl methylcellulose (HPMC), and
carbopol 934 in
insulin-coated capsules revealed no significant difference between the
insulin capsules containing these
polymers, giving relative
hypoglycemia (RH) values ranging from 4.3 +/- 2.3% to 6.5 +/- 5.1%. It was also found that the method of preparation of the mixture of the bioadhesive
polymer with
insulin either by physical mixing or freeze-drying did not affect the RH values obtained.
Sodium salicylate, when used in
insulin enteric-coated capsules (50 mg) mixed with
insulin as a physical mixture, or prepared by wet granulation using 10%
polyvinyl pyrollidone (PVP), or by freeze-drying, produced RH values ranging from 7.3 +/- 2.9% to 9.4 +/- 3.7%. When
sodium salicylate (100 mg) was used with
insulin in freeze-dried granules an RH value of 10 +/- 2.6% was produced. As the dose of
insulin increased from 6 to 9 U/kg, the area under curve (AUC) of the enteric-coated capsules containing 50 mg
sodium salicylate increased from 73.2 +/- 27.8% to 121.4 +/- 102.7% reduction, but the RH did not change significantly.
Insulin capsules containing polyoxyethylene-9-lauryl
ether (POELE) used in its optimum concentration (2%), found in these experiments, produced RH of 9.5 +/- 6.8% when prepared as granules by wetting with a few drops of
absolute alcohol in the presence of PC (50 mg).
Insulin capsules containing lower (1%) or higher (3%) concentrations of POELE and prepared with PC, 50 mg by wet granulation produced lower RH of about 6%. The enteric-coated oral
insulin capsules containing
insulin (6 or 9 U/kg) and
sodium salicylate (50 mg) as an absorption promoter, together with the bioadhesive
polymer polycarbophil (50 mg), and prepared either by wet granulation using
ethanol or by freeze-drying, are the best formulations to be used. They achieved a reduction in plasma
glucose levels of about 25-30% and RH of about 10%. Also
insulin (9 U/kg) capsules containing 2% POELE produced a 28% reduction in plasma
glucose levels and RH of 9.6 +/- 6.8%.