| Objective: Guide by the theory of pharmaceutics, the physico-chemical property of NCTD and absorption characteristic of intestine in rats was mastered. The matrix-diffusion type and membrane-moderated type sustained-release NCTD pellets were prepared.The pharmacokinetics of sustained–release pellets was investigated.Methods:(1) The physico-chemical property of NCTD was mastered by documents. HPLC method was utilized to determine the NCTD content in pellets and release of sustained-release pellets. The dissolubility and n-octyl alcohol /water partition coefficient were determined. The existence condition of NCTD was investigation by spectrums. (2) The intestine in rats was cannudated for in situ recirculation, UV and HPLC were used to determine the concentrations of UV spectrums of phenol red and NCTD, respectively.The absorption of NCTD was studied at different intestine segments, and with different concentration of NCTD. (3) Extrusion-spheronization method was used to prepare pellets. The effects of process variables and formulation variables on pellets preparation and drug release were investigated. (4)A fluid bed spray processor was adopted for coating the pellets of NCTD. The best parameter of machines was controlled. The best coating solution was optimized with uniform design test. The best results were repeated and the data of release curve was fitted.(5)The matrix tablets of NCTD were prepared with HPMC and lactose. The effect of the amount of HPMC and lactose on the release of tablets was studied. The best formulation was optimized with orthogonal experiment. (6)The analytical method of NCTD in vivo was established。The pharmacokinetics parameters was obtained with 3P97.Results: (1) The solubility of NCTD in water is big. The n-octyl alcohol /water partition coefficient decreases when pH increases. (2) The absorption rate constants (Ka) at duodenum, jejunum, ileum, and colon were 0.0306,0.0278, 0.0151, 0.0044h-1, respectively. Ka from intestine at NCTD concentration of 70, 80, 90μg/ml were 0.0499, 0.0525, 0.0489h-1. (3) The main factors affecting the release rate were the type of material applied and the temperature of drying. Release of the drug from pellets was in accordance with Higuchi equation.(4)The best formulation of coating solution: plasticizer 24%,HPMC14%,antisticking agent20%,anstatic agent0.060%.The curve fitting of the best formulation is Ritger-Peppas equation. (5)The best result(100 tablets):HPMC12g,lactose 1.5g,the concentration of alcohol is 90%,the amount of alcohol is 10ml.(6) The Tmax of pellets is 4.49h and the Tmax of tablets is 2.42.The relative bioavailability is 104.5%。Conclusion: (1) The method of HPLC is stable and accurate. It is possible that the sustained-release preparations were designed with NCTD.(2) The concentration of NCTD had no distinctive effect on the absorption kinetics. The absorption of NCTD was a first-order process with passive diffusion mechanism. NCTD was well absorbed at the superior and middle segments of intestine in rats, which indicate that NCTD could be prepared as sustained-release dosage form for administration once a day.(3) The method and the formulation are successful in providing slow and steady release of NCTD from sustained—release pellets.(4)The coating sustained-release pellets with EC release slowly. The type of drug release of the sustained-release pellets is diffusion and corrosion. (5)As the main material of gel-matrix tablets, the HPMC is determinative factor of drug release. (6) The pellets release slowly in vivo compared with tablets.
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