Predicción de la solubilidad del mebendazol en mezclas disolventes / Solubility prediction of mebendazole in solvent mixtures

Los estudios de solubilidad proporcionan una valiosa información que puede emplearse en optimizar el proceso en las fases previas en el desarrollo de medicamentos. En los últimos años, se han desarrollado diferentes métodos de predicción de la solubilidad. En esta investigación se han probado dos modelos de Jouyban con el mebendazol (MB) a 298,15 K en mezclas binarias formadas por etanol y agua y etanol-acetato de etilo. Estos modelos son sencillos de aplicar y resultan muy útiles puesto que sólo se requiere un número pequeño de resultados experimentales. El primer modelo utilizado fue el siguiente: lnXm, = f1 lnX1 + f2 lnX2 + f3 lnX3, B1 (f12f2) + B2 (f1f2) + B3 (f32f2) + B4 (f3f2) (ec.1) en la que, X1, X2, y X3 son las solubilidades del soluto en los disolventes puros 1-3, respectivamente, B1-4 son constantes del modelo. El otro modelo semiempírico de predicción fue: lnXm,T = f1 lnX1,T +(1-f1) lnX2,T +f1 (1-f1) [T T85,254 735,662 (1 ) 1 1 F - - F+ ] (ec. 2)en la que f1 es la fracción de volumen de la mezcla agua-etanol, y T, la temperatura experimental. El tercer término es el factor de exceso de Jouyban-Acree (Factor JA). Los dos modelos semiempíricos de predicción empleados proporcionan una excelente reproducibilidad del perfil de solubilidad. Se concluye que los modelos propuestos, pueden ser útiles en preformulación para predecir el incremento de solubilidad en mezclas disolventes, ahorrando determinaciones experimentales, que consumen tiempo y un importante gasto económico en el diseño de formulaciones líquidas(AU)

Solubility studies provide valuable information that can be used to optimize the process in the previous stages in development of drugs. In recent years, different methods of prediction of solubility have been developed. In this research, two models of Jouyban was tested with mebendazole (MB) to 298,15 K in binary mixtures of water- ethanol and ethanol-ethylacetate. These models are very easy to apply and useful since only a small number of experimental results is required. The first model used was the following: lnXm, = f1 lnX1 + f2 lnX2 + f3 lnX3, B1 (f12f2) + B2 (f1f2) + B3 (f32f2) + B4 (f3f2) (ec.1) where X1, X2 and X3 are the solubility of the solute in the pure solvents, respectively, B1-4 are constant model. The other semiempirical prediction model tested was: lnXm,T = f1 lnX1,T +(1-f1) lnX2,T +f1 (1-f1) [T T85,254 735,662( (1 ) 1 1 F - - F+ ] (ec.2) where f1 is the fraction of the volume of the mixture ethanol-water, and T, the experimental temperature. The third term is the factor of excess Jouyban-Acree (Factor JA). The two semiempirical prediction models employed offer an excellent reproducibility of the profile of solubility. It is concluded that the proposed models may be useful in preformulación to predict increased solubility in mixing solvents, saving experimental determinations, which consume time and economic effort in the design of liquid formulations(AU)

Synthesis and characterization of a new mebendazole salt: mebendazole hydrochloride.

Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ.HCl indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. (

Synthesis and antiparasitic activity of albendazole and mebendazole analogues.

Albendazole (Abz) and Mebendazole (Mbz) analogues have been synthesized and in vitro tested against the protozoa Giardia lamblia, Trichomonas vaginalis and the helminths Trichinella spiralis and Caenorhabditis elegans. Results indicate that compounds 4a, 4b (Abz analogues), 12b and 20 (Mbz analogues) are as active as antiprotozoal agents as Metronidazole against G. lamblia. Compound 9 was 58 times more active than Abz against T. vaginalis. Compounds 8 and 4a also shown high activity against this protozoan. Compounds 4b and 5a were as active as Abz. None of the Mbz analogues showed activity against T. vaginalis. The anthelmintic activity presented by these compounds was poor.