RESUMEN
The purpose of this study was to demonstrate the usefulness and wide applicability of a taste sensor and a new disintegration testing apparatus in the development and/or evaluation of orally disintegrating tablets (ODTs). In this paper, we described methods for the effective utilization of a taste sensor in the development of a new medicine. First we predicted the taste of propiverine hydrochloride, a model drug substance whose taste is unknown, using a taste sensor. Then we screened masking agents for their ability to suppress the bitterness of propiverine hydrochloride, and manufactured ODTs of propiverine hydrochloride with various masking agents. The tastes of these ODTs were then evaluated in chronological order by combining the taste sensor with the new disintegration testing apparatus, ODT-101, to resemble the oral cavity. As a result, we were able to evaluate the taste of propiverine hydrochloride and the effectiveness of various masking agents in ODTs. The result using this combination of taste sensor and ODT-101 shows good agreement with the results of human gustatory sensation testing, thus demonstrating the usefulness and applicability of the taste sensor and disintegration testing apparatus, ODT-101, in the development of new medicine.
Asunto(s)
Bencilatos/farmacología , Química Farmacéutica/métodos , Composición de Medicamentos/instrumentación , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/instrumentación , Evaluación Preclínica de Medicamentos/métodos , Gusto/efectos de los fármacos , Administración Oral , Bencilatos/administración & dosificación , Bencilatos/química , Química Farmacéutica/instrumentación , Humanos , Boca/fisiología , Valor Predictivo de las Pruebas , Saliva/química , Saliva/fisiología , Solubilidad , Edulcorantes/administración & dosificación , Edulcorantes/química , Edulcorantes/farmacología , ComprimidosRESUMEN
The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.
Asunto(s)
Famotidina/química , Saliva/fisiología , Comprimidos/química , Tecnología Farmacéutica/instrumentación , Administración Oral , Humanos , Tecnología Farmacéutica/métodos , Factores de TiempoRESUMEN
The aim of this study was to develop a simple and suitable disintegration method specific for rapid disintegrating tablets (RDTs). The new disintegration method that we propose employs a rotary shaft to exert mechanical pressure on the RDT. To assess our method, we manufactured several placebo RDTs and exposed them to severe storage conditions (60 degrees C/75%RH for 1 week) in order to obtain RDTs with a wide range of disintegration times. These placebo RDTs were utilized to compare the disintegration times obtained by several methods, including the proposed method. As expected, the disintegration time of the placebo RDTs in human sensory test varied widely. The disintegration times determined by the conventional disintegration test were in good correlation to those in human sensory test, but the slope was far from 1 (0.241). There was no correlation between the disintegration time of RDTs in human sensory test and those determined by the conventional dissolution test. In contrast, we acquired good correlation between the disintegration times obtained with the new method and those in human sensory test, and the slope was very close to 1 (0.858). We attribute this to the use of mechanical stress in the new method, similar to that the RDT is subject to in the oral cavity. We therefore concluded that the proposed method was suitable for the measurement of the disintegration time of RDTs. This new method might provide a valuable approach for the establishment of the official disintegration test for RDTs in the future.