Study On Preparation Of Tolterodine Tartrate Polylactic Acid Sustained-release Microspheres

Tolterodine Tartrate, as a new highly competitive M acetylcholine receptorantagonists, is specific and with high affinity for muscarine. Tolterodine Tartrate ismainly used for relieving symptoms of frequent micturition, urgent urination andurgency incontinence caused by detrusor hyperreflexia.In the preformulation study, High Effective Liquid Chromatogram ColumnAnalyzing Method is initiated to determine the loading and in vitro Release ofmedicines. The mobile phase of High Effective Liquid Chromatogram ColumnAnalyzing Method is Phosphate Buffer（80：20）（add3ml phosphoric acid into waterof500ml, and use diethylamine to make sure the pH is7.2）. This method is easy,quick, accurate and reliable. It determined the solubility of model medicine indifferent solvents and the distribution coefficient of oil/water. The result showed thatthe liposoluble of tolterodine is low and thus double emulsion method isrecommended to adopt for microcapsules preparation.The experiment hereby chooses biodegradable polylactide as carrier, adoptsdouble emulsion method of emulsify-solvent evaporation method to preparetolterodine tartrate polylactic acid microspheres, chooses the diameter, loading,entrapment efficiency and in vitro Release of the microspheres as index to evaluatethe factor of the prescription, including the impact of Molecular Weight of PolylacticAcid, amount of emulsifier, concentration of polylactic acid, volume ratio of organic phase/continuous phase, concentration of PVA and electrolytic concentration overTT-PLA-MS preparation. Meanwhile, technological factors are also examined,including the impact of temperature, stirring speed and volatile time over thepreparation of TT-PLA-MS. Based on the result of above experiment, three factorsthat cause significant impact, which are temperature, amount of emulsifier andvolume ratio of organic phase/continuous phase, are selected to form the bestformulation situation by doing orthogonal design experiment. When taking loading,entrapment efficiency and in vitro Release as index, the best formulation is:temperature is30℃, the amount of emulsifier is800μL, and volume ratio of organicphase/continuous phase is1：50.The average diameter of prepared tolterodine tartrate polylactic acidmicrospheres is6.58±0.2μm (n=500), the microspheres with5.0-11.0μm diameterare more than80%of total microspheres. The microspheres are smooth, even and inideal dispersed state when being observed under optical microscope. The loading is(4.6±0.3)%, entrapment efficiency is (80.7±0.4)%, total release dosage in phosphatebuffer（pH7.4）24d is (83.5±0.3)%. These evidence proves that tolterodine tartratepolylactic acid microspheres have good release-controlling performance.