We have previously developed a formulation of oral rapidly disintegrating tablets for hydrophilic model drug ascorbic acid and hydrophobic model drug ethenzamide. Since most of the drugs have some unpleasant taste like a bitter taste, the bitter taste of a drug should be suppressed or masked when developing oral rapidly disintegrating tablets. Therefore, in this work, we aimed to develop oral rapidly disintegrating tablets that can disintegrate rapidly in the oral cavity and suppress the bitter taste of drugs.
A model drug with bitter taste, pyridoxine hydrochloride (VB6), was processed into core particles using water-insoluble polymer ethyl cellulose (EC) or sucrose esters of fatty acids with a low melting point (SE) as the excipient. The core particles were then coated with a powdered mixture of SE and lactose, and compressed into tablets. Oral rapidly disintegrating tablets with rapid disintegration and masking of bitterness was achieved. It was found that the formulation of core particles and the binder composition determine the ability to mask the bitter taste of VB6. The dissolution profile of VB6 from the tablets fitted the Higuchi equation. Accordingly, we supposed that VB6 dissolves quickly from the particular matrix in a diffusion manner, following the fast disintegration of the tablet in the oral cavity.
Scanning electronic microscopy (SEM) observation and differential scanning calorimetry (DSC) found that SE was uniformly spread on the surface of core particles after heat treatment, and thereby the bitter taste of VB6 was masked. Furthermore, heat treatment also made the core particles porous and easily collapsible, facilitating the dissolution of VB6.
DSC measurement of raw material of SE showed that the low endothermic peak of 53.2°C disappeared after the heat treatment of SE, assuming the transformation to stable crystal forms. The heat treatment also increased the mechanical strength of core particles as compared to those untreated, and probably maintained the integrity of core particles during the compression step. SEM observation found much micro-porous structures in the tablets prepared from heat-treated particles, but with no difference to heat untreated tablets in terms of the size distribution of porous structures.
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