Determination and modelling of in vitro release kinetics of mebendazole in simulated intestinal fluid from solid dispersion formulations as infinite reservoirs

Abstract

Mebendazole (MBZ) is a wide-spectrum antihelmintic drug and, more recently, has proven to be active in various types of cancer. In both cases, its efficacy is limited by insufficient bioavailability due to its very low solubility and inadequate release kinetics. This paper presents the preparation and in vitro availability of solid dispersions of MBZ and polyethylene glycol (PEG) 6000, which were combined with Ludiflash as a disintegrant and croscarmellose as a superdisintegrant in tablets, by direct compression processing technology. The release was determined in simulated intestinal fluid, and the kinetics were analyzed using square root, Noyes-Whitney, Peppas, and Weibull models. An improvement of release in a simulated intestinal medium has been achieved due to the formation of solid dispersion and presence of disintegrants, leading to tablet disintegration in about 15 min in the case of 1: 1 solid dispersion and between 30 min and 1 h in the case of 1: 2.5 solid dispersion. The amount of MBZ released was approximately 60% in 3 h for the 1: 1 dispersion, 100% for the 1: 2.5 dispersion, and only 6% for the tablets without PEG. The release was described well and unitary by square root laws in both pre- and post-disintegration phases. The square root model was argued to describe the release from an "infinite reservoir" (i.e., a generalized square root law, similar to those applied in heat transfer) and not released under the conditions of the Higuchi model.