Study On Polymorphism Of Adefovir Dipivoxil

Polymorphs existing in drug system have an influence on making technology, quality and stablition.Diverse physical and chemical properties of polymorphs connect with bioavailability.Controlling polymorphs become an essential issue on the study of drugs.Polymorphs aspectswere carried out in this paper, and adefovir dipivoxil was chosen as the research system,the detailed werefollowed.Form-Ⅰ and Ⅴ was prepared by using solvent-out crystallization method,Form-Ⅸ cooling crystallization.The quantitative analysis of two forms adefovir dipivoxil mixture was measured by Differential scanning calorimetry, Powder X-ray diffraction and Raman spectrometer.Then,the calibration curve was built to quantify the amount of Ⅴ and Ⅰ-form adefovir dipivoxil in powder mixture.The optimized method was compared by calculating relative deviation RE.The solubility of two forms adefovir dipivoxil in mixed solvates which include n-hexane and methylene chloride according to volume ratio 12:1 was measured by a dynamic method. The solubility data is correlated by experience formulation, then,estimatedenthalpy and entropy of dissolution of two forms based on regression of the line.Non-isothermal thermogravimetry was applied to study the thermal decomposition processes of adefovir dipivoxil Ⅰ-form, which include three thermal decomposition stages, thermal decomposition process was just adefovir dipivoxilburning. By getting activation energy E and mechanism function g(α) respectively without any integral error,decomposition mechanism and kinetics function of every stage were obtained.In order to explore growthmechanism, the metastable zone and induction time was measured.The influence factors of metastable zone contain cooling speed and agitation speed, the effect of temperature and supersaturation on induction time were investigated.At last, Nucleation mechanismwas sured on the basis of fitting f(S) and (lnS) correlation coefficient R2.Forms component and solution concentration of adefovir dipivoxil during transformation was analyzed by in-line Raman spectrometer intinal,the result was not reached as supposed.The effect of transformation including seed, agitation rate,temperature,different volume ratio and the ratio of solvate volume and Ⅴ-forms mass was studied by using out-line DSC.Solid transform model mechanismof adefovir dipivoxil Ⅴ-form to Ⅰ-form was sured and crystallization transform rate with different crystal condition at the same time was made a brief analysis. Optimized transform form V to form Ⅰ processing was sured:temperature 30℃、include n-hexane and methylene chloride volume ratio 12:1、seed mass fraction 5%.