PHARMACEUTICAL STUDIES OF POLYACRYLIC ACID AQUEOUS GEL BASES : ABSORPTION OF INSULIN FROM POLYACRYLIC ACID AQUEOUS GEL BASES FOLLOWING RECTAL ADMINISTRATION IN ALLOXAN DIABETIC RATS AND RABBITS

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The effect of gel preparation on the rate of absorption of a rectally administered insulin which was suspended in a polyacrylic acid aqueous gel base (0.1%, pH 6.5) was investigated in the alloxan diabetic rats and rabbits. The preparation was administered into the in situ rectal loop in rats or infused directly into the rectum in rabbits, and the change in the blood glucose level and plasma insulin value was taken as a measure to evaluate the rate of rectal absorption of insulin. The blood glucose lowering effect in both rats and rabbits was dose-dependent, namely, a slight effect was observed at 1 IU/kg followed by a significant effect with 3 and 5 IU/kg, and a sharp hypoglycemic effect was recorded with 10 IU/kg which lasted for 5 hr. The plasma insulin level exhibited a rapid increase at 30 minutes after the dosing of the insulin gel at 3 IU/kg, which is indicative of a facilitated rectal rate of absorption of insulin by the polyacrylic acid aqueous gel base. However, the plasma level quickly diminished in 1 hr. Contrary to our expectation, an addition of a non-ionic surfactant such as Tween 80 under pH 4-8 did not show further enhancement of the absorption. In an attempt to simulate a clinical condition in which insulin was given after a meal, the insulin gel was administered into the rectal loop in diabetic rats following the i.v. injection of glucose. A satisfactory result was obtained in which 5 IU/kg dose was able to suppress a rise in the blood glucose after the glucose loading.
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PHARMACEUTICAL STUDIES OF POLYACRYLIC ACID AQUEOUS GEL BASES : ABSORPTION OF INSULIN FROM POLYACRYLIC ACID AQUEOUS GEL BASES FOLLOWING RECTAL ADMINISTRATION IN ALLOXAN DIABETIC RATS AND RABBITS

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