Research And Development Of Ibrutinib Capsules

Ibrutinib is an BTK inhibitor.It can effectively prevent the tumor from B cells to the lymphatic tissue adapted to the tumor growth environment.In November 2013 ibrutinib was approved by the FDA for the treatment of mantle cell lymphoma,and later in February 2014 for the treatment of chronic lymphocytic leukemia.Ibrutinib is also indicated for the treatment of patients with Waldenstrom’ s Macroglobulinemia(WM).The dosage form of Ibrutinib is capsule,strengths for 140mg.This study aims at of ibrutinib for capsules of the prescription and process research,and quality analysis and stability study on to determine feasibility of prescription.The main contents of this paper is the following:(1)PreformulationTo provide basis for the study of prescription and process,We have studied the pH-solubility,particle size,hygroscopicity,Drug-excipients compatibility of ibrutinib.The results show that:ibrutinib is practically insoluble in water,in 0.1 mol/L hydrochloric acid in the highest solubility was pH dependent dissolution;The compatibility of Excipients combined with ibrutinib is good.(2)Prescription screeningOrthogonal method was performed in order to choose suitable disintegrant,surfactant,lubricant by using dissolution as indexes.The experimental results indicated sodium lauryl sulfate was the chief factor of influencing dissolution of Ibrutinib Capsules.The optimum formulation was composed of croscarmellose sodium 13.2mg,sodium lauryl sulfate 13.2mg,magnesium stearate 1.8mg.(3)Process researchThe preparation of ibrutinib capsules were investigated.Select the dry granulation production of the product,and to observe the process parameters,control API particle size D90 is not greater than 10 microns.Through the test of three pilot scale batches of samples production,to determine the production process,for ibrutinib capsules.(4)quality analysisAnalysis of the key quality indicators of the three pilot scale batches of samples,including dissolution,related substances,assay,weight variation,etc..The analysis showed that the dissolution behavior was similar to that of the original drug,and the other quality indexes were in accordance with the regulations.(5)stability studyTo test the three pilot scale batches of samples to carry on the influence factor,the acceleration,the long-term inspection,the inspection index is the dissolution,the Appearance,assay and related substances.After investigation,all results from the supportive batches are within acceptance criteria and no significant changes are observed。The stability of the product was good.In summary,detailed study of the prescription process,quality analysis and stability aspects,not only to ensure the quality,and to ensure the safety and stability of the clinical use provides the necessary conditions,so this product which we study is detailed and comprehensive.The prescription process of ibrutinib capsule is stable and controllable,is suitable for industrial production.