| Objective:Imitating aspirin enteric-coated tablets for chemical generic drugs,determined the formulation,process and key quality attribute requirementsof aspirin enteric-coated tablets,The in vitro dissolution of test and reference preparations were investigated and the in vivo bioequivalence studies were carried out to evaluate the consistency of quality and efficacy between test and reference preparations.Methods:1.Based on the analysis of the literature and data of reference product,combined with the reverse engineering of the reference product to determine the aspirin enteric-coated tablets of the initial prescription,process and quality control requirements of raw materials.2.Research and examine the particle size distribution,solubility,wettability and other indicators of the purchased aspirin bulk drug,to ensure that the drug substance was available for the formulation research.3.Research and test the conduct dissolution and film dissolution rate of the reference research products to provide guidance for developing test products.4.The prescription screening stage of the test products,through the reverse engineering analysis and confirm the initial prescription,through comparison with the reference research,to explore the model of auxiliary materials in the prescription,the amount of auxiliary materials and the process parameters in the preparation process,the prescriptions and processes with high similarity of release curves were obtained by 16 prescriptions at this stage.5.Small trial production stage,repeat the prescription and process parameters determined in the prescription screening stage to ensure the reproducibility of the formulation and process.6.The pilot production process,to verify the range of the technological parameters,to continuously produce 3 batches of samples in accordance with commercial standards,and to ensure that the quality is consistent with the reference product.7.The fasting and feeding bioequivalence test was evaluated using one batch of pilot-scale test products and two different batches of reference research products(batch number:BJ34297,BJ35000)by a randomized,single-dose and three-cross test design.Results:1.Control the particle size of the drug substance to about 700 mesh 900μm.2.The optimal formulation:Aspirin:100mg;Microcrystalline cellulose G250:15mg;Corn starch:5mg;Eudragit? L30D-55:30mg;Talc powder:9mg;Triethyl citrate:0.9mg;3.Small trial production stage:excipient moisture control:microcrystalline cellulose G250:1.35%,1.44%,corn starch:1.27%,1.58%,mixed for 5min content was 100.4%,RSD was 1.00%,mixed 10min content was 100.1%,RSD was 1.34%,Feed speed for dry granulation:15rpm,Roller speed:l0rpm,Mesh number:20 mesh,Tableting process:pressure:18～24N,tablet weight:± 3%,Coating process:coating weight gain is controlled within the range of 15%～17%,coating parameters:liquid feeding speed:2.7mg/min,tablet bed temperature:28～32 ℃,heat treatment time:60 ℃ 30min,coating time:6～7 hours,gaining between 2%and 3%per hour.The similarity between the reference products and the test products in the in vitro consistency evaluation obtained from the product is higher than 50%.4.Pilot production process:the critical quality attributes of three batches of test products meet the requirements,and the dissolution profile is similar to the reference products.5.Bioequivalence study:The 90%confidence interval of feeding and the fasting studies are both between 80%and 125%.Conclusion:The test products’ preparation formulation is reasonable;the production.process has good reproducibility and stability;The quality of the test products is controllable and conforms with the quality specification of aspirin enteric-coated tablets;The appearance of the test products is the same as that of the reference product(batch number:BJ34297),and the characteristics of in vitro dissolution are consistent.Consequently,the aspirin enteric-coated tablets from this study are bioequivalent with the reference products. |
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