Polymorphic transformation of febuxostat after crystallization in presence of bentonite dispersion: characterization by the heat of fusion and heat of transition rule, and dissolution.

OBJECTIVE

Febuxostat (FBX) has been crystallized using bentonite dispersion as an antisolvent, and characterized by heat of fusion and heat of transition rule for possible polymorphic transformation and improved dissolution.

SIGNIFICANCE

Polymorphic transformation may exhibit significant alteration of melting temperature, solubility, dissolution rate, and stability. FBX is known for polymorphic/hydrate/solvate transformation in many forms wherein stable form has hardly been reported.

METHODS

Aqueous bentonite dispersion was used as antisolvent for crystallization of FBX and characterized by heat of fusion and heat of transition rule, and the effect of bentonite concentration on drug dissolution has also been confirmed.

RESULTS

Monotropic and enantiotropic relationships between the pair of polymorphs have been established with the help of transition enthalpy and transition entropy rule. Energy-entropy interplay showed that the transition occurred above the melting temperature indicating the monotropic relation between the FBX crystal pairs (from A to Q). Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies also confirmed the transformation of A (pure FBX) to Q form and its stability (40 °C, 75%RH, 3 months). The crystallite size was estimated from the graphical plot of major important XRD peaks using the least square method of altered Scherrer equation which is supposed to minimize the error associated with the original Scherrer equation. Williamson-Hall equation was used properly for determining strain from the positive slope avoiding misperception of negative slope.

CONCLUSIONS

Prepared form Q was found stable and displayed drug dissolution in an improved and controlled manner.