Development of liquid oral sustained release formulations of nateglinide: In vitro and in vivo evaluation

The objective of this work was to develop calcium free alginate and alginate/chitosan in situ gelling systems of nateglinide. Nateglinide dispersions containing alginate or alginate-chitosan were prepared in presence or absence of calcium chloride. The viscosity, gelling capacity and drug release were monitored before evaluating the hypoglycemic effect of selected formulations. In situ gel formation was achieved at gastric pH in presence and absence of calcium ion. Chitosan increased the gelling capacity and reduced the rate of drug release in gastric and intestinal phase. The in vivo results revealed extended hypoglycemic effect after administration of calcium free formulations compared to aqueous suspension of the drug. In absence of calcium ions an acid gel was formed as a result of inter and intra-molecular hydrogen bonding with the protonated carboxylic groups playing an important role. This gel dissolves readily in the intestinal conditions. Addition of chitosan strengthened the gel via polyelectrolyte complexation between alginate and chitosan. This gel maintained its strength irrespective to the pH. In conclusion calcium free alginate based in situ gelling system was able to sustain the release of nateglinide with the efficacy being enhanced in presence of chitosan.

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