Physicochemical characterization and solubility enhancement studies of allopurinol solid dispersions

Abstract

Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with treatment of diuretic conditions. One of the major problems with the drug is that it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation, kneading method, co-precipitation method, co-grinding method and closed melting methods to increase its water solubility. Hydrophilic carriers such as polyvinylpyrrolidone, polyethylene glycol 6000 were used in the ratio of 1:1, 1:2 and 1:4 (drug to carrier ratio). The aqueous solubility of allopurinol was favored by the presence of both polymers. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, UV and Fourier Transform Infrared spectroscopy. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure allopurinol, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with polyvinylpyrrolidone showed highest improvement in wettability and dissolution rate of allopurinol. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the present study showed that polyvinylpyrrolidone and polyethylene glycol 6000 have a significant solubilizing effect on allopurinol.Uniterms: Allopurinol. Polyethylene glycol 6000. Solid dispersions. Closed melting method. Dissolution enhancement.Alopurinol é fármaco comumente utilizado no tratamento de gota crônica ou hiperuricemia associada com o tratamento em condições diuréticas. Um dos maiores problemas com o fármaco é que este é praticamente insolúvel em água, o que resulta em baixa biodisponibilidade na administração oral. No presente estudo, dispersões sólidas de alopurinol foram preparadas pela evaporação do solvente, pelos métodos de amassamento, de coprecipitação, de comoagem e fusão fechada para aumentar sua solubilidade em água. Transportadores hidrofílicos, como polivinilpirrolidona, polietilenoglicol 6000 foram utilizados nas proporções de 1:1. 1:2 e 1:4 (fármaco: transportador). A solubilidade aquosa do alopurinol foi favorecida pela presença de ambos os polímeros. Estas novas formulações forma caracterizadas no estado líquido pelos estudos de solubilidade de fase e no estado sólido pela calorimetria diferencial de varredura, difração de Raio-X, espectroscopia de UV e de IV com transformada de Fourier. As caracterizações do estado sólido indicaram que o alopurinol estava presente como material amorfo e embebido em matriz polimérica. Ao contrário da velocidade de dissolução lenta do alopurinol puro, a dispersão do fármaco nos polímeros aumentou consideravelmente a taxa de d...

Formulation and Evaluation of Allopurinol Loaded Chitosan Nanoparticles

“…3. The principal peaks at 3360, 3043, 1705, 1764 and 1593 cm −1 were obtained in the spectrum of AL [20]. The spectra of HMW chitosan showed a broad band at 3416 cm −1 (OH) and sharp peaks at 2956 cm −1 (CH) and 1654 cm −1 (NH).…”

Topical Allopurinol-Loaded Nanostructured Lipid Carriers: A Novel Approach for Wound Healing Management

“…Additional tests will be desirable to confirm if AP present in the NLC is mostly in an amorphous state with only few partially crystallized drug molecules, as scarce information exists on allopurinol-to-lipids interaction. According to the literature concerning solid state characterizations of polymer matrix, allopurinol is present as an amorphous material entrapped in polymers, and this condition considerably enhances the dissolution rate of the drug [ 31 ]. Recent studies have shown that the use of amorphous actives in topical products responsible for higher saturation solubility creates an increased concentration gradient between the formulation and skin, thus improving the diffusive flux into the skin [ 32 ].…”

A Brief Review of Analytical Methods for the Estimation of Allopurinol in Pharmaceutical Formulation and Biological Matrices

“…It is soluble in dilute alkali hydroxides solutions. It is white to almost white, crystalline powder [ 5 ].…”