Promotion of oral insulin absorption in diabetic rabbits using pH-dependent coated capsules containing sodium cholate.
The hypoglycemic effect of oral insulin (40 U) capsules coated with a pH-dependent soluble polymer (Eudragit S100) and containing various doses of sodium cholate (20, 50, 100 mg) was studied in alloxan-hyperglycemic rabbits and compared with that of s.c. insulin injection (20 U). Sodium cholate (20 and 50 mg/capsule) produced a dose-related enhancement of an insulin-induced decrease in the blood glucose level. Insulin capsules containing sodium cholate (50 mg/capsule) produced a steady reduction of the blood glucose level reaching 69% of the initial values (P < 0.01) by 3 h and 48% (P < 0.001) by 5 h after administration. This capsule produced an AUC0-5 h of 125 +/- 14.8 mg.h/dl with relative hypoglycemia (R.H.) of 25.8% compared with insulin s.c. The capsules containing sodium cholate (100 mg), however, did not significantly (P > 0.05) improve the hypoglycemic effect of insulin more than the smaller dose (50 mg/capsule) producing an AUC and R.H. of 135 +/- 12.3 mg.h/dl and 27.9%, respectively. The capsule coated with Eudragit S100 and containing insulin mixed with sodium cholate seems to be a promising formulation to overcome the unavailability of oral insulin.
Hosny
E A
EA
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ghilzai
N M
NM
Elmazar
M M
MM
D000284:Administration, Oral; D000496:Alloxan; D000818:Animals; D002214:Capsules; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D011817:Rabbits
D002214:Capsules; D002793:Cholic Acids; D007328:Insulin; D000496:Alloxan; D019826:Cholic Acid