Preparation And Quality Study Of Cefaclor Sustained Release Tablet Ⅱ Preparation

Cefaclor is an oral cephalosporin antibiotic used to treat respiratory tract infection,urinary tract infection and otitis media.Cefaclor has a rapid absorption and metabolism,to decrease The Times of taking medicine and to improve patients compliance,Lilly companies in the United States developed cefaclor zyban(trade name Ceclor CD),and listed in the United States in 1998.In 2016 the state council issued the implementation of generic quality consistency and efficacy evaluation opinions stated in the 289 varieties of complete consistency evaluation at the end of 289,exceed the time limit of unfinished,will not be registered again.Cefaclor is one of 289 species.Yangtze river pharmaceutical 2013 cefaclor zyban II approval,but the stability of product quality is poor,do not agree with the original in vitro drug release curve,Ceclor CD as the reference preparations,this paper proposed to cefaclor zyban II the preparation prescription of process optimization,on the basis of reference preparations release.The in vitro release degree similarity evaluation.First,in this paper,Ceclor CD was used as the test agent,and different detection methods of cefloclor tablet release in the national pharmacopoeia were used to determine the detection methods of the main drug ingredients for the preparation of sustained-release agents.According to the standard of pharmacopoeia release test,the excipients of sustained-release tablets were determined by single factor test,and the prescription was optimized by orthogonal test.Second,according to the pharmacopoeia slow-release preparation guidelines,in cefaclor API for materials,simulation of the drug in the stomach and intestinal metabolism in physiological environment conditions,as well as the sampling point in time,using spectrophotometry apis in different release medium concentration,determine the release medium,establish API released evaluation system;Using the established release evaluation system and Ceclor CD as reference preparation,the in vitro release curve of slow-release tablets prepared in the laboratory was evaluated.Thirdly,according to the technical specifications of preparation and testing of slow-release tablets,the pre-mixing and drying process parameters of amplification production were studied on the basis of laboratory technology.4 to 30000 pieces/batch of pilot enlarge production scale of the three products,according to the regulations of pharmacopoeia of cefaclor tablets under the test items and methods,combining with the pharmacopoeia of guidance of the principle,the pilot product for regular inspection and controlled-release formulation releasing degree testing analysis methodology research;Fifth,according to pharmacopoeia guidelines,three batches of pilot products were accelerated and long-term stability tests were conducted.40 + 2 ℃,5% RH to75 + and 30 + 2 ℃,5% RH to 65 + 6 months accelerated test,25 + 2 ℃,relative humidity for 60-10% long-term 9 months;Sixth,with the commercial scale of 100,000 pieces/batch,three consecutive batches of products were produced for process verification.The experimental results are as follows:1.The results show that the detection method for the main drug composition of the preparation of the sustained-release agent is the blue method in the first method;The skeleton materials of sustained-release tablets are model K4 M and model E5 of hydroxypropyl methyl cellulose(HPMC).The filling agent is microcrystalline cellulose.The adhesive is 4%polyvinone K30-anhydrous ethanol solution;The lubricant is magnesium stearate.Prescription for: cefaclor(HPMC K4M)/E5 / microcrystalline cellulose(HPMC)/ 4%povidone K30-anhydrous ethanol solution/magnesium stearate = 75/6/7 10/6/1.2.The results show that the established evaluation system of API release includes: water;0.1mol/L hydrochloric acid solution and p H4.0 acetate buffer.Sampling time points: 0.5,1,2,3,4h.Among the three release media,the differential factors f1 were 7,4 and 11,all less than15.The similarity factors f2 were 82,85 and 87,all greater than 50.The results showed that the in vitro drug release curves of the two preparations were similar.3.Determine the premix adopts high speed 180 RPM,10 min,drying parameter is set into the wind temperature 45 ℃,dry and 40 min.4.The results showed that the product traits,contents(> 99%),weight differences(<1.5%),and related substances(maximum single hybrid 0.22% and maximum hybrid 1.1%)were far higher than the national legal standards.The release detection determines the maximum absorption at the detection wavelength of 267 nm,the absorption interference is less than 2%,the linear regression r=0.9999,and the recovery rate is 99.1%,which verifies the accuracy of the release detection method.5.According to pharmacopoeia guidelines,three batches of pilot products were accelerated and long-term stability tests were conducted.40 + 2 ℃,5% RH to 75 + and 30 +2 ℃,5% RH to 65 + 6 months accelerated test,properties changed from white to yellow,rising levels drop,related substances,release,accelerated(but still are conform to the regulations),indicates that this product are more sensitive to hot and humid.25 + 2 ℃,relative humidity for 60-10% nine months for a long time,no exceptions.Medicinal packing for the inner packaging materials were determined: the aluminum foil and polyamide/aluminum/PVC cold stamping forming solid medicinal composite plate composed of double aluminum packaging,this product shall be "shading,sealed,in a cool dark dry place".6.All conform to the quality control standard,confirmed the prescription,process,equipment,instruments,methods of repeatability and stability,the product has entered clinical bioequivalence study,after the product is approved is expected to explore the market for enterprise rapid initial estimates available each year nearly 54 million yuan.This article thoroughly discusses cefaclor zyban generics consistency evaluation,research,quality of prescription optimization,process validation were studied,sustained-release preparations of generic drugs for further consistency evaluation,provides certain ideas and more advanced complete production process.