Studies on spironolactone polymorphic forms

Abstract

The phenomenon of polymorphism of spironolactone was studied using melting point and aqueous solubility determinations, infrared spectroscopy, differential thermal analysis, X-ray powder diffraction and powder dissolution. The results showed that spironolactone crystals obtained from ethyl acetate had the lowest melting range, while those obtained from acetonitrile had the highest range. The aqueous solubility data indicated the presence of different forms of spironolactone, each with a specific solubility, although practically all of these forms could be considered to be water-insoluble. The infrared spectra were not useful in clearly distinguishing between the different forms. Differential thermal analysis curves indicated that some of the forms obtained by treating spironolactone with different solvents were somewhat similar, others were variable, but all of them were different from the original form of the drug. Moreover, the thermal study proved the absence of any solvates. X-ray patterns were different in spacing (d) values and intensities of radiation absorption, confirming the presence of four different forms of spironolactone. The form obtained from ethyl acetate had the highest dissolution rate, while that obtained from acetonitrile had the lowest rate.

Spironolactone is known to crystallize out from different solvents in different polymorphic forms and to undergo structural rearrangements on heating.^{1, 2} The study was mainly concerned with the infrared identification of steroids, and the results showed that sample preparation techniques have a profound effect on the spectra of these steroids.

Florence and Salole³ undertook a brief investigation into the effects of grinding on the crystalline properties of spironolactone. The results showed no major changes in infrared spectrum after grinding, apart from a decrease in resolution of the absorption peaks. The premelting behavior of the drug was altered, which would indicate that grinding significantly affected the spironolactone crystallinity.

El-dalsh et al.⁴ showed that spironolactone co-precipitate with povidone using different solvents such as absolute ethyl alcohol, acetonitrile and chloroform had a different X-ray diffraction pattern which may be explained on the basis of various polymorphic forms.

The purpose of the present work is to carry out studies to specify the number of polymorphs of spironolactone under the crystallization conditions.