Solid state characterization, solubility, intrinsic dissolution and stability behavior of allopurinol hydrochloride salt

Abstract

Since each solid form of an active pharmaceutical ingredient (API) can exhibit particular physicochemical properties, the objectives of this work were to characterize and study the solubility/stability properties of allopurinol hydrochloride salt (ALO-HCl) for the first time. ALO-HCl was obtained through an unreported recrystallization process and studied by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). All characterization techniques were effective for the differentiation of ALO-HCl from the preferred pharmaceutical form (ALO). DSC and TGA studies showed a solid-state conversion from ALO-HCl to ALO upon HCl loss. Solubility and dissolution tests showed that ALO-HCl converts to ALO in aqueous media. Moreover, the effect of the common ion decreased the amount of drug released from ALO-HCl during the intrinsic dissolution assay in HCl medium. The stability studies showed a partial conversion from ALO-HCl to ALO after 6 months of storage. The results indicate that comparative studies between crystalline forms of APIs are of great importance, as they contribute to the understanding of aspects related to the quality of medicines.

Keywords:

• Solid state characterization
• X-ray powder diffraction
• thermal analysis
• Fourier transform infrared spectroscopy
• solubility
• stability

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgments

The authors thank FAPEMIG (APQ-01931-16), FINEP (Refs. 134/08 and 179/12) and CNPq for their financial support and the Laboratory of Crystallography of UNIFAL/MG for the PXDR analysis.

Additional information

Funding

This study was partially financed by the Coordenação de Aperfeiçoamentode Pessoal de Nível Superior – Brazil (CAPES) – Finance Code 001; Financiadora de Estudos e Projetos; Fundação de Amparo à Pesquisa do Estado de Minas Gerais.