| Anethole trithione (ATT, the chemical name is -(p-methoxyphenyl)-3H-1,2-dithiole-3-thione) , which has bIEn applicated in clinic for fifty years and has a broad pharmacological action, used in protecting liver and cholagogue, at present, in domestic and abroad markets the products are all solid oral dosage. According to relate documents, anethol trithione has a low bioavailability because of the drug release in vivo is confined by the character of hydrophobicity.In this thesis, we used cyclodextrin derivate-2-HP-β-CD which has a bIEter water-solubility to clathrate anethol trithione in order to improve water-solubility by the technique of inclusion, and prepared anethol trithione inclusion tablets by the method of power direct compression in order to cut down drug consumption and tmax to improve dissolution and bioavailability.First, we studied the preparation technology of anethol trithione-2-HP-β-CD inclusion ,and established methods of determining the content of inclusion and inclusion rate; the preparation technology of anethol trithione-2-HP-β-CD inclusion tablets was studied and the standard of tablets quality was established; and study on pharmacokinetics was carried out in animal experiments, compare bioavailability with common tablets.According to the results of studies on solution mixing method, grinding method by ball grinding mill and frIEze-drying method, we prepared anethol trithione inclusion by the method of grinding by ball grinding mill. The orthogonal experiment was carried out to select the formation according to the inclusion rate on the base of single-factor inspection, the formation with mole ratio 1:2, mixing rapid 400r/min and time is 1.5h, the concentration of ethanol is 5% is the ideal, and repeat the formation, inclusion rate could achieve 85.61%.In this thesis, methods are established to determine the content of inclusion and inclusion rate. The content was determined by ultraviolet spectrophotometry which was accurate, sensitive; inclusion rate was determined by DSC-ultraviolet spectrophotometry which was accurate, sensitive and bIEter separation, tally with the require of determined the inclusion rate .Quality of the anethol trithione inclusion was evaluated by DSC , solubility, phase solubility and dissolution . DSC showed that the anethol trithione inclusion had bIEn formed; solubility showed that inclusion, physical mixture, crude drug are 6.24±1.46 mg/L, 179.40±1.26,0.39 mg/L; the solubility of inclusion is 460 times as great as crude drug ;phase solubility showed that the pattern of phase solubility picture is AP ; dissolusion obviously improved comparing with physical mixture and crude drug, inclusion by the results of cumulative release test.We prepared anethol trithione-2-HP-β-CD inclusion tables by power direct compression. Optimal formula by drug dissolusion according to the results of the preliminary test and single-factor inspection, the formula with magnesium stearate (0.5%), microcrystalline cellulose (10%), Silica powder (1.5%), low replace hydroxypropyl cellulose (35%)is ideal.We studied the quality of anethol trithione-2-HP-β-CD inclusion tables ,and established the standard of tables quality. According to Chp 2005,we inspected tables'appearance , tablet weight variation and friability, and determined the content and dissolusion by ultraviolet spectrophotometry which was accurate, sensitive; evaluated the stability according to appearance, content and dissolution, the results showed that the tablets'appearance changed in high humidity and highlight and hinted that tablets should be kIEped in the environment of confined, dry and dark.Methods are established to determine the content of anethol trithione inclusion in rabbits plasma. An HPLC method which was accurate, sensitive for determination of anethol trithione in rabbits plasma could be used for determinating bioavailability; investigate relative bioavailability in rabbits using common tablets as control, the results showed that inclusion's and common tablets's AUC are 21.68 ng?h?ml-1, 32.12ng?h?ml-1,tmax are 0.71h, 1.79h, bioavailability was significant improved, and the tmax was cut down.
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