| Captopril(Cap) is one of the angiotensin converting enzyme inhibitor, Which is a commonly-used and relatively effective drug for the clinical treatment of different kinds of high blood pressure diseases. In the research, elementary osmotic pump (EOF) were prepared.Based on the comprehensive pre-formulation research, NaCl, HPMCKis, MCC, lactose were used to make the tablet core. Celluse acetate (CA) , dibutylphthalate (DBP)and polyethylene glycol 400 (PEG-400) were selected as the coating material.Two analystical approaches in vitro were established in study and practiced in different experiments. Captopril exists in the form of disulphide in plasma, so it was first reduced with NaBELt, then it was derivated with OPA and D-phenylalanine.As a result, drug concentration of Cap in the plasma was determined. This method, with high specialness and sensitivity is effective in determing the drug concentration of Cap in plasma.In the paper, physics-chemistry character of Cap and character of CA dissociation membrane were studied.Base on the Stability investi-gatio,good antioxidation was found.lt established foundation for filtrating prescription.The release behavior in vitro of the Cap EOF complied with zero order release rule. Drug release rate was mostly affected by such factors as type and amount of osmotic pressure promoting agent and the amount of PEG-400. To a certain extent, it was less affected by the size of the drug release orifice and pressure of the tablet core .It had nothing to do with the dissolution method and rotation speed. Meanwhile, the effect ofABSTRACTcoating technique on the drug release was studied. The coating formation and process are optimized by orthogonal design ,having the accumulative release amount in 8h and in 2h, the liner correlation coefficient of the accumulative release amount and time ( r ) in 8h as the evaluation standard.mvestigation about the drug release mechanism proved that the release kinetic derives from the difference of the osmotic pressure across the membrance.Studies were also made about the various effect factors on the drug release of Cap MPOP. The results suggested that osmotic pressure promoting agent, pore former and coating weight had marked effect on the drug release, whereas dissolution method, rotation speed and pressure of the tablet core had less effect. By orthogonal experimental design, the best coating formulation was optimized. Investigation about the drug release mechanism proved that the release rate of Cap MPOP was driven by the osmotic pressure difference across the membrane. Compared with MPOP, EOF had no problem of time lag and its drug release was affected by fewer factors and restrictions on certain factors can be relaxed. The drug release of MPOP tended to have the problem of time lag and was affected by more factors, so it was difficult to control in industry production. The stability test results showed that Cap EOP and Cap MPOP is unstable under high temperature and high humidity, whereas good stability was found under light .The accelerating test indicated that the drug content and appearance of the packaged preparation do not changed.With quick release tablets in the market as the reference, studies were made about relative bioavailability and pharmacokinetics study of dogs in vivo by means of HPLC.The Cmax of Cap EOP and reference tablets are 805.1 and 1725.3ng/ml , the Tmax is 6.5h and 1.75L Cap EOP has good correlation between absorption in vivo and drug release in vitro.
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