Absorption Kinetics Of NZTD And Development Of NZTD Sustained-release Tablet

The objective of this study was to develop NZTD gastric retention sustained-release tablet which could steadily release drug in 12 hours in vivo, under the direction of biopharmaceutics.Absorption kinetics of NZTD was studied by method of in situ perfusion of rat before NZTD formulation developed because the preparation of oral formulation could be guided by absorption rate and kinetics. HPLC methods were established respectively to determine the concentration of NZTD in gastric juice and the concentration of NZTD and phenolsulfnphthalein in the intestinal perfusate. The result indicates that NZTD can be well absorbed in stomach of rat and the average absoption rate of high, middle and low dose in 2 hours is 80.9±4.46%, and the absorption of NZTD in intestine of rat is poor. Considering of the pharmacokinetics data of NZTD(T_max is about 1.2h , T_1/2 is about 2h) and its clinical dosage regimen (300 mg·d^-1 or 150 mg, b.i.d, or t.i.d.), we prepared to design its sustained-release formulation, in order to diminish the fluctuation of blood concentration of NZTD and elevate the compliance of patients.The HPLC method was established for the content determination of NZTD in the NZTD sustained-release tablet. The formulation and preparation technology was filtrated by the index of dissolution, granule fluidity and appearance of tablet. Based on the basic formulation , the type and usage amount of main backbone materials was chosen and a certain proportion of disintegrating agent and surfactant was added to adjust the dissolution behavior of the sustained-release tablet. The dissolution profile of 3 bathes of tablet indicate that the dissolution of NZTD sustained-release tablet had well reproducibility and homogenicity and accorded with demond of sustained-release formulation.The identification methods and the HPLC method for the content determination of NZTD were set up in the quality study of the NZTD sustained-release tablet. The dissolution rate at 2 h, 6 h, 10 h was 20～30%,55～65% and above 80% respectively in regulation . The examining method of the correlated material was founded. The studying results according to items of the quality evaluating showed the evaluating method was reasonable and the quality of the NZTD sustained-release tablet was under the control. The release mechanism was studied, the Higuchi equation was the best one. The release parameter of n of Ritger-Peppas equation equals to 0.7529,0.45＜n＜0.89, it means that the release mechanism is the synergism of diffusion and matrix erosion.The stability showed that light had not abvious effect on the NZTD sustained-release tablet but high temperature and high humidity influenced its stability. The result suggested that it should be packed in moistureproof material and stored in dry, cool and shady place.The NZTD sustained-release tablet was prepared based on the absorption kinetics of NZTD in stomach and intestine under the direction of biopharmaceutics. The research result of this study could to be reference of the other dosage form of NZTD.