Preparations And Studies Of Esomeprazole Magnesium Enteric-coated Capsules

Objective:Omeprazole as the first PPI drug,its efficacy in the treatment of acid related diseases has been unanimously recognized.Esomeprazole is the isomer of omeprazole.Mainly in the form of sodium salt and magnesium salt.Esomeprazole magnesium in acidic and neutral media would be degraded,and in acidic environment,degradation is particularly rapid.Therefore,as the oral drug,the destruction of gastric juice is the most obvious,most of the relevant preparations have been used to protect the preparation of the preparation of enteric coated preparation,blocking esomeprazole magnesium and gastric juice direct contact.The stability of the active compound is also affected by the conditions of light,heat and oxygen.Therefore the drug should be preserved at room temperature and away from the light.At present,China’s commercial esomeprazole magnesium enteric-coated capsules only Lesmills Shu.The purpose of this study is to screen different formulations and processes for the preparation of esomeprazole magnesium enteric-coated capsules and to study its quality in order to meet the quality control requirements.Methods:1 Esomeprazole magnesium enteric-coated capsules preparation: in this study,sucrose pellets for blank pellets,the fluidized bed spray coating method in order to prepare the drug layer,isolation layer,the enteric layer was prepared into esomeprazole magnesium enteric coated pellets.In the process of preparing the adhesive layer of the type and dosage of drugs directly affect the pellets on the layer take up rate.Other factors fixed prescription,as the index to study the same fluidized bed parameters take up rate,and ultimately determine the adhesive for HPMC,dosage of 4%.Using aqueous solution ofopadry as isolation layer of coating material,Eudragit L30D-55 dispersions for enteric material,glycerol monostearate as enteric layer anti adhesion agent,prepared by esomeprazole magnesium enteric fluidized bed spray coating for preparation of pellets.At the same time,in order to determine the optimum parameters of the equipment,the single factor experiments was made to investigate fluidized bed process,the investigation object was spray speed,spray pressure,the temperature of the material and the air volume.Observe and study release degree of the pellets,investigate the effect of different thickness of enteric layer,determine the best prescription.Finally,the prepared esomeprazole magnesium enteric-coated pellets were prepared according to the main content of 20 mg into capsules.2 The quality control study of esomeprazole magnesium enteric-coated capsules: To establish a HPLC method for the determination of the release,acid resistance,content,content uniformity and related substances of esomeprazole magnesium enteric-coated capsules and take methodological investigation.Prepare ESO magnesium enteric-coated capsules with the best prescription,and then study the stability of preparation by the influencing factor tests and accelerated tests with the acid resistance,indexes of release,content,appearance and related impurities.The test of influencing factors including high temperature test(60℃ or 40℃),high humidity test(90% ± 5%or 75% ± 5%)and glare test(4500±500 Lx);accelerated test for homemade esomeprazole magnesium enteric capsules,simulated commercial packaging,placed for 6 months at a temperature of 40℃,75% relative humidity conditions,to investigate whether the appearance of samples,sample content,acid resistance,release and related impurities are changed.Results:1 According to the screening and study the prescription,best prescription of the coating liquid of drug loading layer: ESO 20 g,protective agent 0.2 g,HPMC 8 g,water 200 mL.Fluidized bed parameters: air volume 130 m3·h-1,material temperature 34-35℃,spray pressure 1.5-2 kg,spray speed 200-300mL/h.Coating liquid of the isolation layer: The aqueous solution of HPMC(4%).Fluidized bed parameters: air volume 130 m3/h,material temperature36℃,spray pressure 1.5-2 kg,spray speed 200-300 mL/h.Coating liquid of the enteric coated layer: EudragitL30D-55 534 g,TEC14 g,glycerol monostearate 6 g,water 1030 mL.Fluidized bed parameters: air volume 130 m3/h,material temperature 33-34℃,spray pressure 1.5-2 kg,spray speed 100-200 mL/h.2 Established the HPLC method of content uniformity,acid resistance,determination of content,release and related impurities for esomeprazole magnesium enteric-coated capsules.The method is accurate and sensitive;it is applicable to the quality control of the esomeprazole magnesium enteric-coated capsules.3 Carry out the influence factor tests and accelerated tests of the self-made esomeprazole magnesium enteric-coated capsules.90% ± 5% high humidity environment,self-made esomeprazole magnesium enteric-coated capsules and the content had no obvious change;light 4500 ± 500 Lx,no significant changes in capsule and contents;under the condition of high temperature of 60℃,self-made esomeprazole magnesium enteric-coated capsules release decreased.But under 40℃preservation,pellets the quality was stable.Accelerated experiments for 6 months,the capsules were kept stable.The results showed that the esomeprazole magnesium enteric-coated capsules were stable under high humidity and light,but not suitable for high temperature storage.Conclusions:In this study,esomeprazole magnesium enteric-coated capsules were prepared successfully,and the formulation and preparation process of esomeprazole magnesium enteric-coated capsules were simple,feasible and reproducible.The method of content,release and related impurities was established to control the quality of the preparation.The experimental data showed that esomeprazole magnesium enteric-coated capsules could be stored at room temperature for a long time.