Synthesis And Polymerization Reaction Kinesics Of β-Cyclodextrin Polymer, And The Release Study Of Tablets Composed With β-Cyclodextrin Polymer And Slightly Soluble Drugs

This paper is to report my work on the optimization of polymerization betweenβ-cyclodextrin (β-CD) and epichlorohydrin (EP), polymerization reaction kinetics and how theβ-cyclodextrin polymer (β-CDP) influences the tablets release of slightly soluble drugs.Firstly according to the L43 orthogonal table, three factors (β-CD content in reaction system,β-CD / EP molar ration and NaOH water-solution concentration) three levels experiments have been designed to determine the reaction condition for water-soluble and high molecular weightβ-CDP in 50℃reaction system. The result showsβ-CD content in reaction system is the main factor onβ-CD molecular weight. Basing on orthogonal result the optimized reaction condition has obtained by single factor investigation. The optimized reaction condition includesβ-CD content in reaction system 50%(w/v),β-CD / EP molar ration 1:8.9, NaOH concentration 20%(w/w).The product's weight-average molecular weight is MW 57316.6.Secondlyβ-CDP concentration has been measured by viscosimetry on time duringβ-CD / EP polymerization process in 50℃.β-CD / EP polymerization reaction order has been determined to be second order and reaction rate constants under all reaction conditions have been worked out. The reaction rate constant is 0.0022 ml·g-1·min-1 under control on the optimazed condition.Five NaOH concentrations(15.0%,17.5%,20.0%,22.5%,25%)have been used inβ-CD / EP polymerization reactions in 50℃to obtain the best NaOH concentration 20.0%.Finally theβ-CDP (MW 57316.6) has been mixed with aspirin and diclofenac sodium (DS) respectively. The mixtures have been pressed to tablets respectively. Tablets release has been measured by the rotating basket method of dissolution test.The release behavior has described in relation of diffusion equations to the determination of the rate of release of drugs into solution from tablet formulatioin.The release data has also substituted into zero, first, Higuchi and Ritger-Peppas equations respectively. The fitting result is that the release of aspirin tablets fit either first equation or Ritger-Peppas equation, and the release mechanism bases on diffusion and corrosion. The release of diclofenac sodium tablets accords with either zero equation or Ritger-Peppas equation, and the release mechanism bases on corrosion.