Preparation And Quality Control Of Azilsartan Tablets

Objectives: Azilsartan,a novel AT-1 angiotensin II receptor blocker(ARB),mildly reduces blood pressure without nonproductive cough side effect.Azilsartan was introduced by Takeda Pharmaceutical Company Limited in January 2012.In this study,we developed a preparation process of Azilsartan tablets,determined the formula and processing technique,and compared the quality of our products with Azilsartan tablets from Takeda pharmaceutical.As a result,generic Azilsartan tablets were successfully achieved with pharmaceutical equivalence to the references.Methods: Based on comprehensive quality research of the references and the characteristics of quality obtained,the preparation process of Azilsartan tablets has been developed successfully.The original manufacturer of Azilsartan tablets was Takeda Pharmaceutical Company Limited.According to the drug instructions,the fomula compositions were lactose,starch,microcrystalline cellulose,hydroxypropyl cellulose,low substituted hydroxypropyl cellulose,magnesium stearate,polyethylene glycol 6000,hydroxypropyl methylcellulose,two titanium oxide and iron oxide.Through analysis,polyethylene glycol 6000,hydroxypropyl cellulose,titanium dioxide and iron oxide were coating material,whereas the remainings were core materials.Based on the original formulation and the results of excipient compatibility,we designed the formulation and preparation process of Azilsartan tablets.In this research,the formulation dosage of fillers,lubricants and adhesives were screened,while the particle size of Azilsartan,drying temperature,mixing time,coating powder dosage and other parameters were also studied.Using dissolution curve similarity factor(F2)as an indicator,we determined the formulation and preparation process of Azilsartan tablets.To ensure the quality of the Azilsartan tablets,indicators includingappearance,dissolution,related substances and content were studied in detail,whereas the testing methods were also built.The main indicators of quality standards include: appearance,identification,weight variation,dissolution,related substance,content determination.Result: The final formulation and preparation process:1 Formulation(1000 tablets)Azilsartan 40 g,lactose 45.8g,starch 26.0g,microcrystalline cellulose13.0g,hydroxypropyl cellulose 3.9g,L-HPC 0.65 g,magnesium stearate0.65 g.Film coating pre mixed agent 6.0g,purified water 54.0g.2 Process stepAzilsartan and lactose were mixed at the mass ratio of 1:1 and crushed at0.2 MPa by jet mill(D95≤15μm)for use.The remaining lactose,starch,microcrystalline cellulose,low substituted hydroxypropyl cellulose and hydroxypropyl cellulose of the formulation were weighed and sieved(80meshes)for use.Lactose,hydroxypropyl cellulose,microcrystalline cellulose and starch were mixed according to the order from small to large amount then blended with Azilsartan Wee powder to make soft material with purified water as adhesive;18 mesh sieve granulation,60 ℃ drying,18 mesh size.Low substituted hydroxypropyl cellulose and magnesium stearate were added and mixed evenly.The particle content was determined to calculate the theoretical tablet weight.Shaped punch of φ9.1mm×5.1mm was adopted for compression after adjusting pressure and tablet weight.The film coating pre mixed agent was added to the purified water,and the coating solution with solid content of 10% was prepared.The qualified cores were poured to the coating pot and coated.The coating weight gain was about 3.0%-4.0%.Qualified coated tablets were then packed with blister.A comparison of the indicators between self-made tablets and the reference:Dissolution curve: in four different dissolution media,the dissolution curve similar factor between self-made tablets and the reference were allgreater than 50.Related substances: Impurity profile of self-made products and the reference are basically the same,while the content of every single impurity and total impurities were lower than those of the original products.Others: in accordance with Chinese Pharmacopoeia,all indicators of self-made tablets and the reference were compared in sequence.No significant difference was found.Conclusions:The results showed that the indicators such as identification and content of our products were consistent with those of the reference.The related substances of our products were also same as those of the reference with lower content.In addition,the dissolution curve similar factors between self-made and reference preparations were greater than 50 in a variety of solvents,indicating the dissolution behavior of the both samples are basically the same.In summary,it is considered that the self-made Azilsartan tablets and reference are pharmaceutically equivalent.