Relative hypoglycemic effect of insulin suppositories in diabetic beagle dogs: optimization of various concentrations of sodium salicylate and polyoxyethylene-9-lauryl ether.
The effect of insulin suppositories containing different amounts and concentrations of sodium salicylate (50, 100 mg) and polyoxyethylene-9-lauryl ether (POELE 1, 3, 4%), respectively, on the plasma glucose concentration of diabetic beagle dogs was investigated after rectal administration. Comparison of the effects of these formulations was made with that produced after subcutaneous insulin injections. Insulin suppositories containing sodium salicylate (50 mg) produced a maximum reduction of plasma glucose concentration (Cmax) of 55 +/- 11%, an area under the curve (AUC) of 252 +/- 59% reduction h; and a relative hypoglycemia (RH) of 49 +/- 12% relative to subcutaneous injection of insulin (4 U/kg). Increasing sodium salicylate to 100 mg/suppository did not improve the hypoglycemic effect of insulin suppositories further. Investigation of the influence of insulin suppositories containing different concentrations of the nonionic surfactant POELE (1, 3, 4%) showed that; the suppositories containing the lowest concentration (1%) produced the highest hypoglycemic effect with a Cmax of 68%, AUC of 332 +/- 67% reduction h, and RH of 55 +/- 11%. Incorporation of sodium salicylate 50mg in insulin suppositories containing 1% POELE did not improve further the effects found with these suppositories. In conclusion, a relative hypoglycemic effect of about 50-55% can be achieved using insulin suppositories containing Witepsol W35 as a base, insulin (5 U/kg), and sodium salicylate (50 mg) or POELE (1%) as rectal absorption enhancers.
Hosny
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Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. ehosny@ksu.edu.sa
Al-Shora
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HI
Elmazar
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MM
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012980:Sodium Salicylate / Q000008:administration & dosage*; D013488:Suppositories; D014014:Tissue Adhesives / Q000008:administration & dosage
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013488:Suppositories; D014014:Tissue Adhesives; D000077423:Polidocanol; D011092:Polyethylene Glycols; D012980:Sodium Salicylate