Co-processing of nateglinide with meglumine for enhanced dissolution rate: in vitro and in vivo evaluation.
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.
['Bazeed|Alaa Y|AY|', 'Essa|Ebtessam A|EA|', 'Nouh|Ahmed|A|', 'El Maghraby|Gamal M|GM|']
D000818:Animals D003921:Diabetes Mellitus, Experimental D008536:Meglumine D000077715:Nateglinide D051381:Rats D012995:Solubility D017550:Spectroscopy, Fourier Transform Infrared D014961:X-Ray Diffraction
Nateglinide meglumine dissolution rate hypoglycemic effect salt formation