Quantification of Losartan Potassium Polymorphs Using Powder X-Ray Diffraction.

BACKGROUND

Losartan potassium, a common antihypertensive drug on the market, has multiple polymorphs, of which form I is used as a pharmaceutical crystal form. Form I can be partially converted to form III under some circumstances. The quantification of losartan potassium polymorphs is important to control the quality of pharmaceuticals.

OBJECTIVE

To establish a method to determine the contents of losartan potassium polymorphs.

METHODS

Pure form I and form III of losartan potassium were obtained by recrystallization, and characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy, Raman spectroscopy, and thermal analysis. A powder X-ray diffraction method was developed to characterize form I and form III of losartan potassium. Peak area and weight percentage were used to establish calibration curve.

RESULTS

The calibration curve was linear over the range of 1-50% (w/w), using the characteristic peak area ratio of form I at 11.13° 2θ and form III at 5.64° 2θ as the quantitative parameter. The precisions were excellent between 0.6-4.9%, and the limit of quantification was 2.02% (w/w).

CONCLUSIONS

This PXRD method can be used to analyze mixtures of losartan potassium polymorphs (forms I and III) quantitatively and control the quality of bulk drug.

HIGHLIGHTS

This is a new method of quantifying the amount of form III in polymorphic forms of losartan potassium using data obtained by PXRD. It is consistent, sensitive, and accurate.