| Solina succinate tablet has obvious advantages in the comparison of drugs for the treatment of overactive bladder(OAB).At present,the original product is facing patent expiration,and there is no report on the development of domestic generic drug technology.Effective generic drug products are used for domestic market registration.In this paper,the physical and chemical properties,prescription composition,dissolution curve,etc.of the original research reference product are studied to confirm that the original research reference product is a light yellow round film-coated tablet.The self-developed product must maintain the same size and appearance as the original research tablet,No nicks;confirm the dissolution curve behavior of the original reference material in 4 media,the original research tablets dissolve quickly,and the dissolution in 15 minutes of the four media are all close to 85%,no obvious pH dependence,use 0.1M HCl as the distinction medium The nature of the drug substance was studied and it was determined that Solinacin succinate is a highly soluble and highly permeable active ingredient,which belongs to the BCS Class I.Through the degradation experiment,influencing factor experiment and stability experiment of API,it is determined that Solinaxin is unstable to oxidation conditions or alkaline combined oxidation conditions,and is prone to degradation;The light conditions are very stable.Excipient compatibility experiments indicate that the selected excipients include pregelatinized starch,lactose monohydrate,hypromellose,povidone K30,BHT,citric acid,magnesium stearate,Opadry 03B620030 and API Capacitive is ideal and can be used for subsequent product prescription development.In the process of prescription design and prescription screening,different adhesives,wetting agents,antioxidants,lubricants were screened and used,and the amount of coating powder was inspected.The final prescription of the product was determined:internal granulation Part:68.32%lactose monohydrate,12%pregelatinized starch,8%povidone K30,antioxidant 0.02%BHT and 1.33%anhydrous citric acid,isopropyl alcohol as a wetting agent for wet granulation;Granulation part:1%magnesium stearate,6%povidone K30;use Opadry 03B620030/03B640020 coating.On this basis,small-scale process development was carried out on self-developed products,and the amount of wet granulation solvent,wet granulation time,crystal form stability during the production process,etc.were inspected one by one,and each quality index met the target product’s The quality requirements determine the best process parameters for the small test:isopropyl alcohol addition:48g/5000 tablets to 53g/5000 tablets,additional granulation time:120s,drying time:1.5 hours(90 minutes)or more,screen Aperture:φ0.8mm,sheet hardness:6kp(4-8kp).After the successful development of the small trial process,the amplification process was developed according to the principle of amplification of the process parameters,and the key quality attributes during the amplification process were studied,including the LOD uniformity during the granulation process,the fluidized bed drying process,and the whole granulated dry particles,Particle mixing,tablet hardness,tablet speed,tablet process stability,coating process inspection,the experimental results show that the key quality indicators of all batches meet the predetermined acceptable standards,verifying the feasibility of the proposed enlargement process.Finally,the dissolution curves of the four self-developed products and the original research products were compared in the four dissolution media,related substances,and the crystal form of the preparation.The comparison results showed that the dissolution curves in the four media were similar.The characteristic impurities and total impurities of the research product are lower than those of the original product,and the crystal form is consistent.The results showed that the self-developed solina succinate tablets had the same quality as the control preparation. |
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