Co-processing of nateglinide with meglumine for enhanced dissolution rate: in vitro and in vivo evaluation

Abstract

Objective

The aim of this work was to investigate dry co-grinding of nateglinide with meglumine for enhanced dissolution rate of nateglinide. The study was extended to investigate the effect of this dissolution enhancement on the hypoglycemic effect of the drug in diabetic rats.

Methods

Nateglinide was subjected to dry co-grinding with increasing proportions of meglumine to prepare products containing the drug with meglumine at 1:1, 1:2, and 1:3 molar ratios. These products were evaluated using combined instrumental analysis which employed Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). Drug dissolution was also monitored before and after processing with and without meglumine. The optimum ratio was used to assess the effect of dissolution enhancement on the hypoglycemic effect of nateglinide on diabetic rats. The unprocessed nateglinide was used as control.

Results

Co-grinding of nateglinide resulted in changes in the FTIR spectral patterns of nateglinide and meglumine. The changes suggested the formation of amide bond between both compounds at 1:1 molar ratio. The new species was confirmed by DTA and XRD. This species exhibited fast dissolution of nateglinide after incorporation of higher proportions of meglumine. Co-grinding was essential as indicated from slower dissolution from physical mixture containing the highest proportion of meglumine. Enhanced dissolution was reflected in vivo as improved rate and extent of hypoglycemia.

Conclusion

Dry co-grinding of nateglinide with meglumine developed new species which liberated nateglinide rapidly and enhanced the rate and extent of hypoglycemia of nateglinide.

Keywords:

• Nateglinide
• meglumine
• salt formation
• dissolution rate
• hypoglycemic effect

Ethical approval

The in vivo study employed male albino rats. The study protocol and animal treatment were revised and approved by the College of Pharmacy, University of Tanta Ethical Committee.

Disclosure statement

The authors declare no conflicts of interest.