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

Abstract

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.

Multilayer Films Based on Chitosan/Pectin Polyelectrolyte Complexes as Novel Platforms for Buccal Administration of Clotrimazole

“…The sharp endothermic peak at 147.59 • C corresponding to the crystal melting point of CLO [62] was recorded (Figure 2). The second one (272.01 • C) might have indicated possible contamination of the sample as, according to Garcia Ferreira et al [63]., decomposition of the drug typically occurs above 340 • C. Similar to the previous scientific reports [64][65][66], the protective effect of the electrostatically interacting polymers on the active substance resulting from inclusion of the drug inside PECs can be observed as no peaks indicating the process of the drug decomposition were recorded. The absence of CLO melting point might have also resulted from undetectable drug amount in the films, crystallinity reduction or transition of CLO to its amorphous form as a result of the solubilizer (PEG 400) addition.…”

Development of an UPLC-MS/MS Method for Quantitative Analysis of Clotrimazole in Human Plasma Samples

“…According to other HPLC methods [16,17], our method uses a column temperature of 40 • C. In addition, according to the stability study of Patricia Garcia Ferreira group [18], the sample of CTZ was dried at 40 • C.…”

Sporotrichosis: a case series from a reference center in the Amazon

“…The therapeutic choice depends on the clinical form of the disease, the immune status of the host, and the species involved 23 . At present, in Brazil, the drugs available are itraconazole, potassium iodine (KI), terbinafine, and amphotericin B 6 .…”