Estudos químico-farmacêuticos de formas sólidas de alopurinol

Abstract

Allopurinol (C5H4N4O) is an active pharmaceutical ingredient (API) widely used in the treatment of hyperuricemia and gout. It is a drug classified as class IV in the biopharmaceutics classification system (BCS). There are descriptions of three crystalline solid forms of allopurinol in the Cambridge database: freebase (ALOBL), allopurinol hydrochloride (ALOCL) and allopurinol hemisulfate. Since each solid form of an IFA can exhibit particular physicochemical properties, studies in IFAs about the effects of solid state variations on the quality of raw materials and medicines are of great relevance. Thus, the main objective of this work was to obtain at least one solid form of allopurinol different from the commercialized form and to perform characterization, accelerated stability, solubility and intrinsic dissolution studies. For studies involving quantitative analysis, a stability-indicating high performance liquid chromatography (HPLC) method was optimized and validated. Validation studies showed that all parameters meet ANVISA resolution RDC no. 166/2017. ALOBL has been identified in the raw materials and ALOCL was obtained from recrystallization of ALOBL in 0.1 mol.L-1 hydrochloric acid. The results of characterization by infrared spectroscopy (IR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the techniques are effective for differentiation of the studied forms. Solubility studies have shown that ALOCL is more soluble than ALOBL at 37 ° C in pH 4.5 and 5.4 media after 48 hours of study. However, the solubility of both forms was equal after 72 hours probably due to the conversion of ALOCL to ALOBL. Intrinsic dissolution studies revealed that ALOCL showed lower dissolution rate than ALOBL at pH 1.2 due to the common ion effect. Accelerated stability studies have shown that ALOCL partially converts to ALOBL after conditioning up 6 months under described conditions. Considering that some methods for synthesis and purification of allopurinol described in the literature use hydrochloric acid, there is a possibility of formation of ALOCL in raw materials. Thus, this work contributed to the understanding of important aspects related to the quality of allopurinol. Therefore, chemical and pharmaceutical studies of different solid forms of an IFA are of great relevance for ensuring the quality of drugs and medicines.