Predictive In-Vitro Evaluation of Food Effect on The In-Vivo Performance of Chlorpropamide Tablet

Abstract

This study compared the disintegration time and dissolution profile of the hypoglyceamic drug product, chlorpropamide marketed in Nigeria as Chlorbinese in simulated gastric fluid (SGF), simulated intestinal fluid SIF, and in food modified gastric fluid (FMSGF) and intestinal fluid (FMSIF) as a measure of the effect of dosing condition on in-vivo drug performance.

Various quality control parameters including weight uniformity, tablet hardness, disintegration, friability and assay were assessed prior the dissolution profile determination. Food containing media was prepared by blending 1.3ml full cream fat containing milk and 25mg of soluble starch  added to 500ml and 300ml of SGF and SIF to make FMSGF and FMSIF respectively, mimicking human gastric and intestinal content after drug administration. The in-vivo performance of the drug at the dosing conditions was also determined using 24 healthy volunteers with post dosing administration of drug and blood sampling at time intervals.

The titrimetric and spectrophotometric assays gave 99.37% and 104.12% of chlorpropamide content respectively (P<0.05). No significant differences were observed between the disintegration time for FMSGF, SGF, SIF and FMSIF being (5s, 4s ,4s and 6s) respectively at P<0.05. There was no significant difference in the percentage drug release in FMSIF compared with SIF (40% v 35%) similarly there was  no difference in the release rate for media simulating dosing conditions in the stomach revealing (28% v 28%) release at P<0.05. There was no significant difference in the change in blood glucose level in the volunteers with respect to the dosing conditions P<0.05.Dosing conditions did not affect the drug release and blood glucose reduction of chlorpropamide tablet.