Effect of bioadhesive 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 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%.
Hosny
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Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ehosny@ksu.edu.sa
al-Shora
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Elmazar
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D000179:Acrylates / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004285:Dogs; D004337:Drug Carriers; D004339:Drug Compounding; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D065347:Hypromellose Derivatives; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000737:chemistry*; D012980:Sodium Salicylate / Q000737:chemistry*; D013608:Tablets, Enteric-Coated
D000179:Acrylates; D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic; D001786:Blood Glucose; D002214:Capsules; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D013608:Tablets, Enteric-Coated; D000077423:Polidocanol; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C030312:calcium polycarbophil; D008747:Methylcellulose; C453622:carbopol 934P; D012980:Sodium Salicylate