The objective of this study was to develop oral bilayered film comprising a drug-containing mucoadhesive layer and a drug-free protective layer. The mucoadhesive layer was composed of a mixture of drug and γ-polyglutamic acid (γ-PGA), and the protective layer was composed of a mixture of cellulose acetate (CA) and hypromellose (HPMC). The bilayered film was prepared by laminating the protective layer onto the mucoadhesive layer. This bilayered structure was expected to provide unilateral drug delivery to oral mucosa and to avoid loss of drug due to salivary flow in the oral cavity. Lorazepam (LOR), a mild tranquilizer in the class of drugs known as benzodiazepines and described as effective for patients with psychiatric maladies, was used as a model drug in this study. From the SEM observation of the surface of the protective layer, it appeared that the shape of fine pores and the pore size and distribution were well controlled by altering the mixing ratio of CA and HPMC. The water absorption behavior and the disintegration time were affected by the mixing ratio of CA and HPMC: an increase in the amount of CA increase the amount of water absorbed and an increase in the amount of HPMC shortened the disintegration time. Furthermore, an increase in the amount of HPMC accelerated the release of LOR through the protective layer. These results indicate that the laminating of the protective layer onto the mucoadhesive layer seems to be effective to prevent the loss of LOR caused by salivary flow.
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.
There have been several reports about compatibility in the mixing of eye drops. A large part of the reports examined the mixing of two kinds of eye drops, and then observed only visual changes in appearance after mixing. To assess the compatibility, we attempted to develop an examination by mixing artificial tears with eye drops. In addition, we measured the number of minute particles and the contents of drugs. We selected 14 combinations that were used in our hospital for outpatients. By adding the artificial tears, the number of minute particles and the contents of drugs were improved. As a result, this method with artificial tears was helpful to evaluate compatibility in mixing eye drops.