Investigation On The Test Method For The Release Of Nifedipine Modified-release Tablets

Nifedipine,as a clinical first-line antihypertensive drug,has significant antihypertensive effects.The drug has small individual differences,and has a clear antihypertensive effect on all types of hypertension in all ages.Nifedipine is a short-acting preparation.After clinical use,patients may experience large fluctuations in drug plasma concentrations after oral administration,resulting from a short half-life of 1.7-3.4 h only.It leads to adverse reactions such as hypotension,insufficient blood supply to the brain,tachycardia,palpitations,headaches,etc..Therefore,slow-release preparation of nifedipine is often clinically used currently.Nifedipine modified-release tablets can not only achieve the same therapeutic effect,but also have the characteristics of stable action,long duration and high anti-hypertensive peak-to-valley ratio.The effect of nifedipine modified-release tablets vary depending on the manufacturer.But the dissolution and release of drug is a best in vitro replacement experiment to predicting bioavailability of drugs in vivo.Therefore,the investigation of the release of nifedipine modified-release tablets is usually used to evaluate the batch-to-batch quality of products and differentiate products from different production processes.Most of the current domestic standards for nifedipine modified-release tablets use paddle apparatus.While the paddle apparatus is weak in distinguishing the products from different companies.In this work,which combined the standard of nifedipine modified-release tablets in foreign pharmacopoeia,we investigate the release of nifedipine modified-release tablets by using the reciprocating cylinder apparatus.And will made a comparison of these two methods.This thesis is divided into five chapters,the main contents are as follows:The first chapter introduced current status of hypertension and its therapeutic drugs.At the same time,it also expounded the significance of investigating the drug dissolution and release.And briefly introduced the history and advantages and disadvantages of various dissolution and release test devices.Moreover,the clinical application of nifedipine and the current domestic and international standards for nifedipine modified-release tablets were also summarized and compared.We hope that the discussion on the two methods for measuring the release rate of nifedipine modified-release tablets will provide reference for the development and quality control of nifedipine modified-release tablets.Meanwhile,it is hoped that the establishment process of reciprocating cylinder apparatus of nifedipine modified-release tablets can be used as a reference for the promotion and application of this method in China.The second chapter investigated the release of nifedipine modified-release tablets using the paddle apparatus.A total of nine samples from three companies were selected.According to the method of dissolution and release of the 2015 Chinese Pharmacopoeia,the filtrates were respectively taken at 4,8,12,16 and 24 h,and the average cumulative release percentage was plotted against time.It was found that the paddle method can control the quality stability of the batch products of the same enterprise,but the products produced by different enterprises using different production processes are very indistinguishable.The third chapter investigated the release of nifedipine modified-release tablets using the reciprocating cylinder apparatus.The condition of measuring the drug release is determined by using the cumulative amount released as an indicator to select dissolution medium and reciprocation rate using reciprocating cylinder apparatus.0.9% Tween 80 in phosphate buffer(pH=6.8)was finally selected as dissolution medium and 10 times/min as reciprocation rate.These dissolution conditions are more reasonable,operability and scientific.At the meantime,the reciprocating cylinder apparatus can also control the quality stability of batch products.And can distinguish the products from different production processes.The fourth chapter compared the paddle apparatus with reciprocating cylinder apparatus.This chapter introduced the release of nifedipine modified-release tablets abroad.It was found that the release test method for nifedipine modified-release tablets in China is single and general,and it is urgent to develop a new and more targeted method.After experiments,it is found that the reciprocating cylinder apparatus has better distinguishing ability than the paddle apparatus.The reciprocating cylinder apparatus can distinguish products from different production processes.It can not only ensure the safety of clinical medication,but also can promote companies to optimize their processes to get better quality products.However,not all nifedipine modified-release tablets can use the reciprocating cylinder apparatus.The most appropriate method should be selected according to its specific prescription,process and in vitro release behavior.The fifth chapter summarized the research results of this thesis and proposed the direction of further research work.