Development of a Method for the Quantification of Clotrimazole and Itraconazole and Study of Their Stability in a New Microemulsion for the Treatment of Sporotrichosis

Molecules

Carolina Guimarães de Souza Lima¹  MarcelaCristina de Moraes¹  Fernandode Carvalho da Silva¹  LetíciaLorena Noronha²  Débora Omena Futuro²  Vitor Francisco Ferreira²  Patricia Garcia Ferreira²  Alessandra Lifsitch Viçosa³ 

[1] Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Niterói-RJ 24210-141, Brazil;Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal Fluminense, Niterói-RJ 24241-000, Brazil;Fundação Oswaldo Cruz (FIOCRUZ), Farmanguinhos-Manguinhos, Avenida Sinzenando Nabuco 100, Rio de Janeiro-RJ 21045-900, Brazil;

关键词: pre-development process;    clotrimazole;    itraconazole;    stability;    method validation;    sporotrichosis;   

DOI  :  10.3390/molecules24122333

来源: DOAJ

【 摘 要 】

Sporotrichosis occurs worldwide and is caused by the fungus Sporothrix brasiliensis. This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be effective against S. brasiliensis yeasts. This association was formulated as a microemulsion containing benzyl alcohol as oil, Tween^® 60 and propylene glycol as surfactant and cosurfactant, respectively, and water. Initially, the compatibility between clotrimazole and itraconazole was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (PXRD). Additionally, a simple and efficient analytical HPLC method was developed to simultaneously determine the concentration of clotrimazole and itraconazole in the novel microemulsion. The developed method proved to be efficient, robust, and reproducible for both components of the microemulsion. We also performed an accelerated stability study of this formulation, and the developed analytical method was applied to monitor the content of active ingredients. Interestingly, these investigations led to the detection of a known clotrimazole degradation product whose structure was confirmed using NMR and HRMS, as well as a possible interaction between itraconazole and benzyl alcohol.

【 授权许可】

Unknown