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Tasteless mosapride resin composite Orally Disintegrating Tablets

Author: SunYunDong
Tutor: ZhangXiangRong；LiSanMing
School: Shenyang Pharmaceutical University
Course: Pharmacy
Keywords: Mosapride Citrate ion exchange resin taste masking orally disintegrating tablets in vitro disintegrating time in vitro release
CLC: R944
Type: Master's thesis
Year: 2009
Downloads: 24
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Abstract

Gastrointestinal tract disease is a kind of common, frequently-occurring disease, the incidence rate is about 60%. Prokinetic agents are widely used in functional dyspepsia (FD), reflux esophagitis (GERD), such as the treatment of chronic gastritis. Mosapride, a selectively serotonin (5-HT4) receptors agonist, is mainly used in clinical functional dyspepsia. It was first developed by the Dainippon Sumitomo Pharma Co., Ltd. and post-marketed first in Japan in December 1998. The approved formulations is available at dose of 2.5 mg/tablet,5 mg/tablet and 1% powder, known as Gasmotin. At present, oral solution formulations at label amount 5 mg/tablet,5 mg/capsule and 5 mg/10 mL oral solution have been approved in the USA Japan market. But orally disintegrating tablet is not approved or reported. In order to facilitate patients to swallow the drug, we studied and prepared Mosapride Citrate orally disintegrating tablets with good taste.Mosapride resinate (MR) were prepared, in order to get higher drug loading and drug availability, the factors such as ethanol aqueous solution concentration, drug concentration were studied. The method was optimized with MC concentration of 0.8 mg·mL-1, the ratio of drug and resin was 2:1, the resin particle size of above 300 mesh and the operation temperature was 288 K. In this condition, the drug availability and drug loading was 99.0% and 1.5g·g-1 respectively. MR was characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), the result showed mosapride combined with IER in a chemical way. Thermodynamics and kinetics of the ion exchange process were studied also, data showes thermodynamic equilibrium constant (K) was decreases with temperature and the values of reaction enthalpy (△Hθ) was-10.345, indicated that more efficient adsorption will be reached at lower temperature. The best fit of experimental data shows that the adsorption kinetics of ion exchange can be described by second-order model, and the second-order rate constant(k2) decreases with temperature also which confirmed the result of the thermodynamics, so the temperature of the ion exchange was set at 288 K.The MR tablet was designed to be orally disintegrated by direct compression (DC) method and wet granulation (WG) method respectively. For DC method, the excipients of the formulation were screened by studied their character. Based on the single factor design, the optimized formulation (each tablet contains MR suitable amount, mannitol 98 mg, MCC 74 mg, LHPC 20 mg, sodium stearyl fumarate lmg, orange flavor 0.5 mg) was get by the response surface method, the oral disintegration time of the optimized formulation was 18 seconds. For WG method, the optimized formulation (each tablet contains MR suitable amount, mannitol 172 mg, MCC 12 mg, CCMC-Na 8 mg, sodium stearyl fumarate 1 mg and 3% pvp water solutions suitable amount) was obtained by orthogonal design method, the oral disintegration time was 17 seconds.The in vitro disintegration time was studied by modified dissolution tester methods, modified disintegration apparatus method, glass-surface vessel methods and magnetic stirring methods. The result indicated that the glass-surface vessel methods and the modified disintegration apparatus method were both suitable for the two different kind of tablets, stirring methods was just suitable for fast dissolving tablets. The effect of taste masking and sandness feel was evaluated by six volunteers, it was found that the resin can mask the bitter taste perfectly; the tablets prepared by WG methods with no sandness feel, but the tablets which prepared by the DC methods has slightly sandness feel.The release of mosapride contained in the orally disintegrating tablets was studied according to the appendix XC (third method) of Chinese Pharmacopoeia 2005 edition. The effect of dissolution medium, dissolution conditions on the drug release were investegated, the data showed the release of drug could reach to 100% in 0.1 mol·L-1 HCl solutions within 10 minutes, which implied the tablets can release rapidly in the similar environments such as in stomach. The studies of the drug release in vitro showed that the release rate was increased with the decreased of the resinate particles size. The release of mosapride from the resin particles was controlled by a particle diffusion process according to Viswanathan’s equation.

Tasteless mosapride resin composite Orally Disintegrating Tablets

Abstract

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