The Research On Pharmaceutics Of Small Molecule Anticancer Drug LY989

LY989 capsules are mainly used in the treatment of hormone receptor-positive advanced breast cancer.On the basis of reference to foreign original preparation,this topic has carried on the imitation research according to the domestic demand,LY989 capsules similar to the dissolution behavior in vitro of the reference preparation were prepared.An ultraviolet spectrophotometry method for the determination of the dissolution rate of LY989 capsules was developed and validated.The concentration of LY989 was good linear with absorbance(4.016~29.116 ?g/mL,r=0.9996).The recovery was between 98% and 102%,and the RSD of the precision test was less than 2%,which indicated that the method was simple,quick and specific.At the same time,the dissolution of the reference preparation in four dissolution media was investigated,and the preparation process of the preparation was determined as dry granulation.Referring to the kind of excipients of the reference preparation,microcrystalline cellulose and lactose were selected as the filler,silica as the glidant,magnesium stearate as the lubricant and sodium carboxymethyl starch as the disintegrant.The effects of many factors including formulation and procedure on the dissolution of LY989 capsules were investigated.At the same time,the best prescription was screened by orthogonal test.In addition,three batches of samples were prepared using the optimized formulation,and the optimized formulation was validated.The results showed that the self-made sample was consistent with the dissolution behavior of the reference preparation,and reproducibility was good.The dissolution curves of self-made samples and reference formulations under different dissolution media(0.1 mol/L hydrochloric acid solution,pH4.5 acetate buffer solution,pH6.8 phosphate buffer solution,water)were investigated,the similarity factor(?2)method was used to evaluate the similarity,the results showed that the dissolution behavior of self-made samples was similar to that of reference formulations.At the same time,the homogeneity of the dissolution of the same batch of samples and the reproducibility of the dissolution between multiple batches of samples were compared,the results showed that the homogeneity and reproducibility of self-made samples were good.A preliminary study on the quality standard of the capsule was conducted,such as trait,identification,volume difference,dissolution test,content determination and so on.The results showed that the content of LY989 capsules was light yellow powder or granules,the UV-Vis spectrophotometry and HPLC were used to identify them,and checking the gross deviation met the requirement for capsules in the Chinese Pharmacopoeia of 2015 edition.The content of LY989 capsules was determined by high performance liquid chromatography(HPLC),and its method was validated.The results showed that the linear relationship between LY989 concentration and peak area was good in the range of 2.5~80 ?g/mL.The recovery was between 98% and 102%,RSD of the precision test was less than 2%,indicating that the method was fast,accurate and specific.