Research And Development Of Nifedipine Controlled-release Tablets

Objective:Based on the original product of Bayer AG,a generic formulation of nifedipine controlled-release tablets was developed to achieve the pharmacological equivalence of key quality attributes such as in vitro release profiles and bioequivalence in vivo.Methods:1.Based on the literature investigation of nifedipine controlled-release tablets,the prescription composition of the original research product(trade name:Adalat(?))was obtained as the reference basis for the formulation design of the self-products;2.Combined with the literature,research and examine solubility,stability,particle size from commercially available nifedipine bulk drugs,to ensure compliance with the relevant standards and meet the needs of preparation study;3.Analyze the key quality attributes of the original product,such as the release degree and content,as the main evaluation indicators of the research and development process of the self-made products;4.In the small-scale research phase,referring to the prescription product composition and design of the dosage form,it is planned to use high-shear wet granulation process to prepare the drug-containing layer and the booster layer granules,press the double-layer tablets,control the release coating,film coatin and glaser perforation to obtain small test prescription sample.Using the paddle method+sedimentation basket,100rpm speed as the release method,and f2 similarity factor as the evaluation method,the similarity of the release curve in a pH6.8 phosphate buffer solution containing 1.0%sodium lauryl sulfate was evaluated,to conduct a pilot test screening and process durability review,and to scale up the pilot test to determine the pilot test process;5.The pilot-scale equipment which is consistent with the principle of the small scale production equipment is used to carry out the pilot-scale research,to verify the range of the technological parameters,to continuously produce 3 batches of samples,and to ensure that the quality is is consistent with the original product;6.Three batches of pilot test samples and one batch of original research product(batch number:BJ30140)were simultaneously examined for influencing factors,acceleration,and long-term test stability;7.The bioequivalence test was carried out with one batch of pilot-scale samples(batch number:39-190701)and one batch of original research product(batch number:BJ30140)by single dose,double cross,double cycle test design.Results:1.The purchased drug substance needs to be further pulverized by jet mill before proceeding;2.The best formulation:Nifedipine:31.5mg,hypromellose E5:7mg,polyoxyethylene(low viscosity):118mg,85%ethanol solution:appropriate amount,magnesium stearate:0.5mg,polyoxyethylene(high viscosity):45mg,red iron oxide:4.0mg,chlorine Sodium chloride:35mg,hypromellose E5:0.5mg,85%ethanol solution:appropriate amount,magnesium stearate:0.5mg;3.The small test stage process:mixing 5min,10min content were 104.70%,and 104.57%,RSD values were 0.79%and 0.63%,respectively,the preparation of purified water was controlled at a stirring frequency of 400 rpm,a shear frequency of 1000 rpm,and granulation for 1 min,and a 24 mesh nylon screen.The drying process controlled the moisture to less than 4%,and the total mixing time was 104.33%and 104.41%,respectively.The RSD values were respectively is 0.61%and 0.57%,and the pressure of the tableting process is controlled:70-90 N,slice weight difference between ±4%,the weight gain of the the controlled release coat is between 14.0%and 17.0%,and the weight of the film coat is between 5.0%and 6.0%;4.The test items of the pilot scale amplification sample meet the quality requirements;5.In vitro consistency evaluation:the dissolution curve of the self-product in different media is similar to the original research(f2>50);6.Pilot samples have good stability;7.The results of the bioequivalence test showed that the confidence interval between the product and the original product(batch number:BJ30140)after meals was between 80%and 125%.Conclusion:The self-products preparation formulation is reasonable;the production process has good reproducibility and stability;The quality of the self-produced products is controllable and conforms to the quality standard of risperidone tablets;The appearance of the self-product is the same as that of the original research product,and the characteristics of dissolution in vitro are consistent.Both self-products and original research product are bioequivalent.