Preparation And Study Of The Taste-masking Type Of Cefprozil Dispersible Tablets

Objectives:At present,the dosage forms of cefprozil for clinical use are tablets and dispersible tablets.Since its bitter taste,the market product without masking taste has poor patient compliance.Particularly,pediatric patients' will to take the medication is very low,which affects the normal treatment.Therefore,the development of the taste-masking type of cefprozil dispersible tablet can improve the taste and patients' compliance,which makes treatment success.Methods:1 The preparation and study of the taste-masking type of cefprozil dispersible tablets: We put proportional cefprozil,glyceryl monostearate,PEG4000 into temperature controlled high-speed stirring granulator,stirring the materials,heating the materials to 65?,setting impeller speed 120 rpm,cutter speed 1500 rpm.After formation of granules,we pass cold water to make granules cool,and maintain stirring until the fusion agent hardens.,we get the taste-masking granules through sieving the particles.We weigh prescription proportional cefprozil taste-masking granules,microcrystalline cellulose,sodium carboxymethyl starch,aspartame,flavors,magnesium stearate,mixing the materials for 20 minutes in a mixer,compressing tablets,packaging and boxing the qualified tablets with aluminum blister.2 Research on quality control of the taste-masking type of cefprozil dispersible tablets: we establish a HPLC method to determine the dissolution,content,related substances and polymers of the taste-masking type of cefprozil dispersible tablets,and do methodological study.3 Research on stability of the taste-masking type of cefprozil dispersible tablets: According to the Best prescription,we prepare the taste-masking type of cefprozil tablets.With the appearance,content,dissolution,related substances as an index,we do influence factors tests,accelerated test and long-term test to study its stability.Results:1 With dissolution as an index,we have determined the best prescription and preparation process of the taste-masking type of cefprozil tablets,according to the results of single factor investigation.The best prescription is: cefprozil 250 mg,glyceryl stearate150 mg,PEG4000 50 mg,microcrystalline cellulose 50 mg,sodium carboxymethyl starch 20 mg,magnesium stearate 2mg,aspartame 2mg,flavor 2mg.2 We have established an HPLC method to determine the dissolution of the taste-masking type of cefprozil tablets and the detection wavelength is 280 nm.Methodological study results show that there is a good linear relationship between the concentration and peak area.The excipients and solvents don't interfere the determination.The stability,precision,recovery meet the quality requirements,so this method can be used for taste-masking type of cefprozil tablets dissolution determination.3 We have established a HPLC method to determine the content of the taste-masking type of cefprozil tablets,and the detection wavelength is 280 nm.According to methodological verification,excipients and solvents don't interfere the determination.There is a good linear relationship between the drug concentration and peak area.The regression equation and correlation coefficient for cefprozil(Z)is Y = 272.36 X + 3.7906,r = 0.9991;and for cefprozil(E)is Y = 442.65 X + 0.2744,r = 0.9992.The stability,precision,recovery,repeatability all meet the requirements.So this method is simple,accurate,sensitive and can be used for quality control of the taste-masking type of cefprozil dispersible tablets.4 We have established a HPLC method for determining related substances of the taste-masking type of cefprozil tablets.Filler is octadecylsilane bonded silica;mobile phase A is 0.23% solution of ammonium dihydrogen phosphate;mobile phase B is methanol;with gradient elution,the flow rate is 1.0ml / min.According to the results of relative material examination,the formulation have three impurities: hydroxyphenylglycine,retention time is approximately 4 minutes;cefadroxil,retention time is approximately 8 minutes;7-PACA,retention time is approximately 10 minutes.5 We have established a HPLC method for determining the polymer of the taste-masking type of cefprozil tablets.The filler is Sephadex G2000PW;the mobile phase is 0.1M pH7.0 phosphate buffer;flow rate is 0.8ml/min;detection wavelength is 254 nm.The sensitivity,precision and stability of the method for detecting polymers are all meet the requirements of 2010 version Chinese Pharmacopoeia.6 According to the results of influencing factors test,the appearance,content,dissolution and related substances of the tablets shows no obvious change in the conditions of 90% relative humidity,high temperature(60?),illumination(4500Lx),accelerated test and long-term test.The results show that the preparation is stable in the condition of high temperature and illumination,but we should take measures to avoid moisture in the long term storage.Conclusions:The taste-masking type of cefprozil tablets have strong operability.It is easy to realize industrial production,with good reproducibility.The medium test results show that the prescription and preparation process of the product are feasible,and the finished products meet the relevant regulations and quality standards of the tablet Principles of 2010 version Chinese Pharmacopoeia.Referring to national drug standards of cefprozil dispersible tablets and related documents,we have formulated quality standards for this product,according to the results of quality test and stability test and the tablets principles of 2010 version Chinese Pharmacopoeia,to ensure the quality control of the drugs.