The Study Of Quality Standard Of Nanoparticles Of Docetaxel For Injection

Objective:Nanoparticles as a novel drug delivery vehicle. They have so many advantages, such as, improved absorption of oral unstable drugs and poorly soluble drugs, prolonged drug circulation time in vivo, increased the capacity of the drugs through the biof ilm barrier, increased drug targeted and so on. that are widely used in the field of anti-tumor. At production and preparation,transportion and storage of nanoparticles, leakage may occur, which could produce harmful degradation products. Currently, there is no uniform quality standards for the nanoparticles preparation. In this parper, studied of quality control technology of nanoparticles of docetaxel for injection, nanoparticles’physical and chemical properties (including nanoparticles appearance, size distribution and zeta potential, acid value, peroxide value), assay, encapsulation efficiency, in vitro release, residual solvents, harmful impurities lysophosphatidylcholine detection, to provide reference quality control for nanoparticles preparation.Methods(1)Studied of physicochemical properties of nanoparticles of docetaxel for injection;Evaluation of the appearance of nanoparticles;Determination of particle size distribution and zeta potential of nanoparticles used dynamic light scattering instrument and Static light scattering method;study of acid value and peroxide value of nanoparticles;(2)Used HPLC method to assay of nanoparticles of docetaxel for injection, and established methodology validation;(3) Studied the separation methods of free drug and nanoparticles to evalue nanoparticles’encapsulation efficiency; Studied of ultracentrifugation, microcolumn centrifugation, sephadex column chromatography and dynamic dialysis method to separate free drug and nanoparticles, choosed the most suitable method for determining entrapment efficiency of nanoparticles of docetaxel for injection.(4) The determination of the condition release in vitro of nanoparticles of docetaxel for injectionAccording to the third mehod of dissolution in the second2010edition of "Chinese Pharmacopoeia", dialysis bag with suspension of nanoparticles was fixed on the stripping small oar, put it in the mediumto sudy the release codition of nanoparticles.(5) Determination of the residual ethanol by different injection methods of GC.(6) Determination of the content of lysophosphatidylcholine with two different types detector of high performance liquid chromatography,ultraviolet detector and evaporative light scattering detector.ResultsThe appearance of nanoparticles of docetaxel for injection was white freeze-dried lumps and color uniformity;The average particle size of nanoparticles of docetaxel for injection was about117nm, and particle size that more than200nmwas less than5%, Zeta potential was about-3.54mv measured by dynamic laser scattering method;Acid value not more than2and peroxide value not more than3;The assay of nanoparticles of docetaxel for injection was9.94mg·g-1using the HPLC method;Preliminary study on vitro release of nanoparticles, and according to cumulative release in vitro release was fitted for order all kinetics equation;The contect of residual ethanol in nanoparticle preparation was0.2%by the headspace gas chromatography method, that accordance with ICH;Extractiing phospholipid composition by ultrasound and centrifugal and then detected the contect of lysophosphatidylcholine, that was0.24%by HPLC-ELSD method, while it wasn’ t detected using HPLC-UV method.ConclusionThe established methods of nanoparticles of docetaxel for injection, such as the physicochemical properties, assay, encapsulation efficiency determination using dynamic dialysis-HPLC, the condition release in vitro, the detection content of harmful impurities of lysophosphatidylcholine is feasible, reliable and controllable, that could provide basis for the quality standard reference of nanoparticle preparation.