RESUMEN
The pharmacokinetic evaluation of guar gum-based colon-targeted tablets of mebendazole against an immediate release tablet was carried out in human volunteers. Six healthy volunteers participated in the study and a crossover design was followed. Mebendazole was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablets. On oral administration of colon-targeted tablets, mebendazole started appearing in the plasma at 5 h, and reached the peak concentration (C(max) of 25.7+/-2.6 ng/ml) at 9.4+/-1.7 h (T(max)) whereas the immediate release tablets produced peak plasma concentration (C(max) of 37.2+/-6.8 ng/ml) at 3.4+/-0.9 h (T(max)). Colon-targeted tablets showed delayed t(max) and absorption time, and decreased C(max) and absorption rate constant when compared to the immediate release tablets. The results of the study indicated that the guar gum-based colon-targeted tablets of mebendazole did not release the drug in stomach and small intestine, but delivered the drug to the colon resulting in a slow absorption of the drug and making the drug available for local action in the colon.
Asunto(s)
Antinematodos/administración & dosificación , Antinematodos/farmacocinética , Colon/metabolismo , Mebendazol/administración & dosificación , Mebendazol/farmacocinética , Adolescente , Adulto , Algoritmos , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Sistemas de Liberación de Medicamentos , Galactanos , Semivida , Humanos , Masculino , Mananos , Gomas de Plantas , Solubilidad , ComprimidosRESUMEN
The present study was carried out to find the in vivo performance of guar gum-based colon-targeted tablets of metronidazole as compared to an immediate release tablets in human volunteers. Six healthy volunteers participated in the study and a crossover design was used. Blood samples were obtained at different time intervals and the plasma concentration of metronidazole was estimated by reverse phase HPLC. The immediate release tablets of metronidazole produced peak plasma concentration (Cmax of 2990 +/- 574.6 ng/mL) within 2.8 +/- 0.6 h. On oral administration of colon-targeted tablets, metronidazole started appearing in the plasma between 5 h and 8 h, and reached the peak concentration (Cmax of 1940.0 +/- 528.4 ng/mL) at 11.1 +/- 2.1 h (Tmax). The AUC(0-infinity) and t(1/2) of metronidazole were unaltered on administering the drug as a colon-targeted tablet indicating that the extent of absorption and elimination were not affected by targeting the drug to the colon. However, colon-targeted tablets showed delayed tmax and absorption time (ta), decreased Cmax and decreased absorption rate constant as compared to immediate release tablets. This in turn indicated that metronidazole was delivered to the colon resulting in a slow absorption of the drug and making it available for local action in the colon.
Asunto(s)
Antiprotozoarios/administración & dosificación , Antiprotozoarios/farmacocinética , Colon/metabolismo , Excipientes , Galactanos , Mananos , Metronidazol/administración & dosificación , Metronidazol/farmacocinética , Adolescente , Adulto , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Sistemas de Liberación de Medicamentos , Femenino , Semivida , Humanos , Absorción Intestinal , Masculino , Gomas de Plantas , Solubilidad , ComprimidosRESUMEN
The objective of the present study is to develop colon targeted drug delivery systems for mebendazole using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The amount of mebendazole released from the matrix tablets at different time intervals was estimated by a high-performance liquid chromatography method. Guar gum matrix tablets released 8-15% of the mebendazole in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids the matrix tablets containing 20% of guar gum released another 83% of mebendazole after degradation into 2-3 pieces. The matrix tablets containing 30% of guar gum also released about 50% of mebendazole in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that matrix tablets containing either 20% or 30% of guar gum are most likely to provide targeting of mebendazole for local action in the colon. The mebendazole matrix tablets containing either 20% or 30% of guar gum showed no change either in physical appearance, drug content or dissolution pattern after storage at 45 degrees C/75% relative humidity for 3 months. Differential scanning calorimetry indicated no possibility of interaction between mebendazole and guar gum.