The Research On The Preparation And Quality Of Palbociclib Capsules

Palbociclib is an inhibitor of CDK4/6 which studied by Pfizer.It is used in the treatment of female patients with ER positive breast cancer in clinical.Because of its outstanding effect in clinical trials,the U.S FDA approved its listing on February 3th,2016,and its brand name is Ibrance,and in the first year its annual sales was more than$700 million,which has a huge market value.At present,palbociclib have not been listed in any other country yet except the United States,also there are no relevant reports of its preparation both at home and abroad.In this paper,the capsule prescription,production technology,its quality standard and stability were studied according to the drug instructions.In the prescription and prescription technology research process,the prescription was selected by orthogonal test method and formulation technology was preliminary determined based on physical and chemical properties of raw materials.Finally the optimum prescription and production process were determined by the appearance of the particles,the fluidity and the dissolution of the capsules,which was palbociclib 7.5g,microcrystalline cellulose 11g,lactose monohydrate 5.6g,sodium carboxymethyl starch 1.59g,colloidal silica 0.26 g,magnesium stearate 0.55 g for 100 capsules.3%sodium carboxymethyl starch as adhesive for wet granulation.Drying at 60℃,then fill the capsule.In order to investigate the prescription and preparation process of rationality and stability,the quality of the three batch of product finished in the optimum prescription and preparation process was detected.The quality of the results are in accordance with the provisions.Related substances,content and dissolution were main detection indicators for the quality standards of products which were tested by the new established dissolution method and HPLC method for the product content and related substances.And the new method were given in the corresponding methodology validation,verification results showed that new method met the requirements of the relevant methods which could be used for quality detection capsule of this prescription and its prescription craft.A preliminary study on the stability of the product was carried out on the basis of the relevant guidelines of the Pharmacopoeia.Respectively the influence factors test,accelerated test and long-term test were carried out to investigate the changed of appearance,moisture content of the product.The results showed that the products were more sensitive to light as the related substances were.increased under strong light.Besides,under the condition of high temperature,the moisture content changes greatly.Therefore,the products were suitable for storage in a cool ventilated and light-avoiding environment.The results of accelerated and long-term experiments showed that each index of the samples changed little,which indicated that the samples prepared by the prescription and production process were relatively stable.