Effect of bio-adhesive polymers, sodium salicylate, polyoxyethylene-9-lauryl ether and method of preparation on the relative hypoglycemia produced by insulin enteric coated capsules in diabetic beagle dogs.
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 bio-adhesive polymers, sodium salicylate and non-ionic surfactants. A comparative study of the bio-adhesive 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 a relative hypoglycemia (RH) values ranged from 4.3 +/- 2.3% to 6.5 +/- 5.1%. It was also found that the method of preparation of the mixture of the bio-adhesive 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 ranged 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 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 id not significantly change. Insulin capsules containing polyoxyethylene-9-lauryl ether (POELE) used in its optimum concentration (2%), found in these experiments, produced a RH of 9.5 +/- 6.8% when prepared as granules by wetting with few drops of absolute alcohol in 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 28% reduction in plasma glucose levels and RH of 9.6 +/- 6.8%.
Hosny
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EA
Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia.
al-Shora
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HI
el-mazar
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MM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D004285:Dogs; D005079:Excipients; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers; D012980:Sodium Salicylate / Q000737:chemistry*; D013608:Tablets, Enteric-Coated; D014014:Tissue Adhesives / Q000737:chemistry*
D001786:Blood Glucose; D002214:Capsules; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D013608:Tablets, Enteric-Coated; D014014:Tissue Adhesives; D000077423:Polidocanol; D011092:Polyethylene Glycols; D012980:Sodium Salicylate