| Extract from the leaves of Ginkgo biloba., as the effective part of herb, is widely used for treatment and prevention of cardiovascular and cerebrovascular diseases, which has the advantage of good therapy and little side-effect. To act further quickly and be suitable to industrial production, a fast release droppill was designed and prepared with polyethylene glycol 6000(PEG6000).Firstly, UV spectrophotometry was developed for the stability and dissolution experiments of EGb or EGb preparation in different pH solution; complexing-colorimetry spectrophtometry was developed for determining the flavone glycosides of EGb in order to select formulations and measure intestinal absorption. Choosing Rutin and Quercetin as standard sample respectively, HPLC with UV detection was applied to evaluate stability and quality of EGb or EGb preparation and to analysis the plasma sample in dogs. The methods above are accurate, liable, convenient and rapid, which all reach the requirement of measurement.In the preformulation researches, the physicochemical properties of EGb were investigated, which were connected closely with pharmaceutic form design. The result that the absorption of EGb by UV in distilled water, 0.1mol/L HC1 and pH6.8 phosphate buffer appeared no change showed better stability of EGb in these mediums and the study on solubility showed that the equilibrium solubility in the above three kinds of mediums were 0.30, 0.22, 0.30g/mL, respectively. The apparent oil-water partition coefficient(Papp) decreased with the increase of pH value in different pH n-octanol/water systems and changed violently about pH3.0. The melting range of EGb was 153.5-191.6 C; the critical relative humidity(CRH) was about 80%. In addition, the chemical stability of EGb was observed and the result indicated that exposure to air, light, humidity and temperature 40 C had little effect on it, but under temperature 60 C, the content of the flavone glycosides in EGb reduced. The determination ofpowder properties showed that the EGb powder had bad fluidness.To clarify the absorption of EGb from gastrointestine, the absorption rate constant, the absorption amount and the absorption percentage were measured by utilizing the rat intestinal recirculating method in situ. The result suggested that the mechanism of the rat intestinal absorption of EGb was via passive diffusion method by investigating absorption in lumen solutions with different concentrations. The experiment in different intestinal parts including duodenum, jejunum and ileum found that the absorption in the utter intestine was better, and best in the duodenum.Droppills were prepared in this process: disperse EGb into the excipients by melting and drip the molten suspension into the condensation fluid, then drops were contracted, cooled and solidified into droppills. By the criterion of particle size, droppill weight, degree of circularity and dissolution rate, the amounts range of EGb and excipients were obtained through single factor experiment. The formulation was optimized on the basis of three factors and three levels orthogonal design by evaluating time of dissoluting 50 percent(T50) and the dripping condition was optimized using the same design by assessing mean variance of weigh. EGb droppills were prepared according to the best components and dripping condition. The repeatability of three batch samples and stability of accelerating test showed that fast release EGb droppills were stable, quality-controlled and met the purpose and requirement of dosage form design.In the study of fast release mechanism, EGb-PEG6000 solid dispersion and physical mixture were analyzed by phase diagrams drew through measuring melting point and DSC method. Both analytical methods suggested that EGb and PEG6000 interact in molten state to form some kind of complex. Solubility of EGb in different concentrations of PEG6000 aqueous solution and dissolution rate of dispersions which had a range of EGb concentrations were investigated. Related to dissolution models, the result was spec... |
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