Study On Formulation And Preparation Of Pomalidomide Capsules

Pomalidomide Capsules are solid oral preparation,for treatment of patients with multiple myeloma who have received at least two prior therapies,including lenalidomide and bortezomib,and have demonstrated disease progression on or within 60 days of completion of the last therapy.Pomalidomide Capsule was developed by US Celgene(Celgene),approved by Food and Drug Administration(FDA)on February 8,2013,and obtained marketing authorization by The European Agency for the Evaluation of Medicinal Products(EMA)on August 2013.Strength:1mg/capsule,2mg/capsule,3mg/capsule and 4mg/capsule,trade name:Pomalyst~?.We imitated pomalidomide with the following specifications:dosage form:capsule,Drug specification:4 mg by refer to RLD product formulations,specifications and combined with the RLD clinical dosage.The present research was designed to study pomalidomide capsule formulation and preparation process by stability study to provide the basis for industrial production.This thesis is divided into five chapters,the main contents include the following chapters.Chapter 1 Introduction.In this chapter,we introduced the pomalidomide capsule mechanism and characteristics,the registration situation and the market prospect of the domestic and foreign research and development,and briefly described the significance of the research and research ideas.In this study,the formulation process of the capsule was investigated from the aspects of the analysis of the original research,the compatibility of raw materials,the prescription screening,the particle size investigation,the process research,the prescription process validation and the stability study.Chapter 2 Formulation study of pomalidomide capsules.Between capsules and RLD,we set the consistency of in vitro dissolution behavior as an evaluation index,determined the prescription of pomalidomide capsules by formulation selection,scale-up batch validation and pilot batch validation.Final determined prescription containing pomalidomide 4.0 g,mannitol172.4 g,pregelatinized starch 60.0 g and sodium stearyl fumarate 3.6 g in per 1000 capsules.Chapter 3 Process study of pomalidomide capsules.Using dissolution and related substances as evaluation index,selected by process route investigation,pomalidomide particle size research and environmental humidity influence study,we determined the process parameters for pomalidomide capsules.The process is as follows:API particle size distribution:D90<10?m,D50<5?m;environmental humidity controlled within RH 60%.In mixing pocess,adding the prescribed amount pomalidomide and 1/3 pregelatinized starch,mixed fully through 60 mesh,then added the prescribed mannitol by mixing 5 min,finally added the remaining amount of pregelatinized starch by mixing 5 min with dry granulation,24 mesh sieve.Plus the amount of prescription sodium stearyl fumarate,a mixture of 5 min,filling in 2#gelatin hollow capsule.Chapter 4 Stability study of pomalidomide capsules.In this chaper,stress condition test,long-term test and accelerated test results showed that,there's no significant difference in products'performance,assay,related substances and dissolution during the stability study.Our in-house products'stability is good.Chapter 5 Conclusion.The main experimental results are summarized in this chapter.Further experimental investagations were proposed and future prospects were speculated.