Study On The Prescription Process Of Isosorbide Mononitrate Extended-release Tablets

Isosorbide mononitrate(isosorbide 5-mononitrate)is a new generation nitrate lipid antianginal drug developed by Astra Zeneca in the UK.Its chemical name is 1,4:3,6-dianhydro-D-sorbitol-5-Mononitrate can promote the relaxation of vascular smooth muscle and dilate blood vessels,dilate the veins to reduce the return of blood in the veins,thereby reducing the load on the heart.Isosorbide mononitrate is characterized by no liver first-pass effect,complete and rapid absorption through the gastrointestinal tract,and bioavailability of almost 100 %.Clinically,isosorbide mononitrate sustained-release tablets are suitable for long-term treatment of coronary heart disease,prevention of vasospasm and mixed angina,as well as treatment after myocardial infarction and long-term treatment of chronic heart failure.At present,isosorbide mononitrate sustained-release tablets have been widely used in many countries in the world,and its clinical effectiveness and safety have been fully affirmed by the clinic.In this project,Astra Zeneca Pharmaceutical Co.,Ltd.'s product Imdur 60 mg tablet(listed in China)was used as a reference listed drug,and the isosorbide mononitrate sustained-release tablets,which were bioequivalent and stable in quality,were developed by imitation.Research method: By analyzing the prescription and quality of the reference listed drug,combining the original cooking properties of isosorbide mononitrate and screening the excipients for the compatibility test of the original excipients,the type of excipients selected for the prescription is initially determined;The types and dosage of agents and lubricants are screened to determine the final prescription of this product is hydrogenated vegetable oil,lactose,hydroxypropyl cellulose,micronized silica gel,magnesium stearate,talc and ethanol.The key preparation process conditions of each process were investigated,and the dissolution rate,particle size,tablet hardness,appearance,etc.were used as the inspection indicators to determine the final granulation time of 1 min and the dry granulation speed of 3500 rpm.Dry moisture is ?1.0 %,drying temperature is 45 ?±5 ?,mixing time is 10 min,particles with qualified uniformity,qualified moisture,good fluidity and tableting requirements can be obtained;the hardness of the tablet is determined to be 60 N-100 N,coating weight gain is1.0 %-3.0 %,the appearance of the obtained product is smooth,the color is good,and it is similar to the dissolution of the reference preparation.The verification of small and pilot production shows that this process is stable and feasible,and provides a basis for industrial production of this product.In this test,by examining the stability of isosorbide mononitrate sustained-release tablets,it was placed under accelerated conditions and long-term conditions for 6 months respectively.Its appearance,shape,in vitro dissolution,related substances and contents were compared with the 0-day samples,No significant difference,in line with quality standards.The results show that the quality of isosorbide mononitrate sustained-release tablets is stable.In this experiment,the isosorbide mononitrate sustained-release tablets obtained by the final prescription and preparation process are stable in process and the quality meets the standards.The similarity of the dissolution curves of the commercially available isosorbide mononitrate sustained-release tablets in the four dissolution media is similar.In which20190401 batch of F2 similarity factors are 72.9,67.1,65.4,61.8;it is proved that the self-developed agent is of the same quality as the reference preparation,the safety and effectiveness are basically the same as the reference preparation,the prescription process can achieve industrial production,Realizing value for the company and the society can bring the gospel to the majority of patients with coronary heart disease.