RELATIVE PHYSICAL STABILITY OF THE SOLID FORMS OF AMILORIDE HCL

Amiloride HCI is available in two polymorphic dihydrate forms, either of which can be dehydrated to an anhydrous crystalline form. The anhydrate rapidly rehydrates to polymorph A of the dihydrate upon exposure to ambient relative humidity. The polymorph A and polymorph B dihydrates have similar melting points, FTIR spectra, and solubilities. X-ray powder diffraction can differentiate the two polymorphs, and quantitative estimates for mixed phase samples can be obtained. This technique was used to show that the composition of USP grade material varies by both vendor and lot number. Polymorph A was found to be more physically stable than polymorph B by using X-ray powder diffraction to follow solid-state transformations upon milling or compressing both forms.