Novel tablet formulation of amorphous indomethacin using wet granulation with a high-speed mixer granulator combined with porous calcium silicate

摘要

Solid dispersion techniques are useful for improving the dissolution of poorly water-soluble drugs. This study aimed to produce and evaluate solid dispersion tablets improving the solubility and oral bioavailability of a poorly water-soluble indomethacin (IND) by wet granulation method with a highspeed mixer granulator combined with porous calcium silicate (PCS). A low density of PCS is a major disadvantage which is a bulky volume and scattering. So, it is necessary to prepare a high density PCS granule. Our system is very simple. At first, IND ethanol solution was added to PCS in a high-speed mixer granulator. After mixing, the granulation started the addition of the binder water solution to the PCS/IND mixture. The solid dispersion granules were obtained after drying the mixture. The dissolution rates of IND from PCS tablets were markedly enhanced compared with the dissolution rate of the pure drug. IND did not recrystallize in granules prepared using water and this formulation provided superior bioavailability in rats. Our amorphous solid dispersions have been successfully employed to enhance both solubility and oral bioavailability of IND. Though the use of PCS, it may be possible to maximize the bioavailability benefit of amorphous solid dispersions administered as tablet dosage forms. (C) 2016 Elsevier B.V. All rights reserved.