Hypoglycemic effect of oral insulin in diabetic rabbits using pH-dependent coated capsules containing sodium salicylate without and with sodium cholate.
The hypoglycemic effect of oral insulin (20 U and 40 U) capsules coated with a pH-dependent soluble polymer (Eudragit S100) and containing sodium salicylate (50 mg) without and with sodium cholate (50 mg) was studied in alloxan-hyperglycemic rabbits and compared with that of s.c. insulin injection (20 U). The capsules containing 20 U insulin + sodium salicylate (50 mg) produced a significant reduction in plasma glucose level to 82 and 73% of initial values at 2 and 3 hr after administration, respectively. The blood glucose level slowly returned to normal values at 5 hr. The AUC0-5 hr was 73.7 +/- 43.5 mg.hr/dl compared to 242 +/- 70.5 mg.hr/dl for insulin (20 U, s.c.) with a relative hypoglycemia of 30.4%. A higher dose of oral insulin (40 U) + sodium salicylate (50 mg) was more effective in reducing plasma glucose level which steadily decreased and reached 56% of the initial value by 5 hr (AUC0-5 hr = 132 +/- 41.5 mg.hr/dl and relative hypoglycemia = 27.3%). Sodium cholate (50 mg), however, slightly improved sodium salicylate effect producing an AUC0-5 hr of 139 +/- 37.3 mg.hr/dl with relative hypoglycemia of 28.7%. The relative hypoglycemia of pH-dependent coated capsules reached in the present experiment is the highest found so far.
Hosny
E A
EA
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ghilzai
N M
NM
al-Najar
T A
TA
Elmazar
M M
MM
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D020358:Sodium Cholate; D012980:Sodium Salicylate
D001786:Blood Glucose; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D020358:Sodium Cholate; D012980:Sodium Salicylate