A Preliminary Study On The Key Process Of Omeprazole Enteric-Coated Tablets

As the first generation of proton pump inhibitors,omeprazole has been on the market for more than 30 years.Its physical and chemical properties,mechanism of action,pharmacokinetics and pharmacodynamics have been relatively clear.The traditional preparation technology of enteric coated tablets has been quiet skillful,and provides theoretical basis and technical support for the development of generic drug.Because of the different drug release behavior between generic preparations and reference preparations in vitro,which may lead to the failure of clinical bioequivalance.This paper intends to determine the best prescription technology of omeprazole enteric-coated tablets through the optimization of the prescriptions and processes,and to prepare qualified and stable omeprazole enteric-coated tablets,which's multiple dissolution curves is similar to the reference preparation's in vitro.The details are as follows.HPLC was used to analyze the content and related substances of omeprazole,and UV to analyze the dissolution of omeprazole enteric-coated tablets.These two methods are reproducible and accurate,which can be used as quality analysis methods of omeprazole enteric-coated tablets.By investigating the solubility and stability of omeprazole in different pH medias,and establishing a method for comparing the similar dissolution curves of self-made formulations with reference formulations,and then through excipient compatibility tests,we found these series of pre-prescription studies provide the basis for prescription optimization.To prepare omeprazole core tablet,it was used lactose for filler,light magnesium oxide for pH alkaline regulator,sodium starch glycolate?CMS-Na?for disintegrant,sodium lauryl sulfate?SDS?for wetting agent,magnesium stearate for lubricant,and hydroxypropyl cellulose?HPC?is for binder.Using single factor method,and particle size distribution,hardness,disintegration,dissolution,related substances,etc.are used as indicators,to optimize the prescription and process parameters of the core tablets.The best core formulation is:light magnesium oxide accounts for 37.5%of omeprazole,CMS-Na,SDS,magnesium stearate account for 5%,1%and 1%of the prescription,the concentration of the HPC is 2%,the core hardness is 3 kg.The obtained omeprazole core was coated with hypromellose?HPMC?as a release layer and hypromellose phthalate?HPMCP?as an enteric layer.The related substance,acid acid resistance in acidic medium of pH 1.2 medium,multiple dissolution curves are similar?The average drug dissolution of omeprazole enteric-coated tablets within 15 min>85%in pH 6.0 and pH 6.8medium,while the similarity factor f₂>50 of the dissolution curves between self-made omeprazole enteric-coated tablets and reference preparations in water medium?were the main indicators.The optimal coating formulation process was determined by adjusting the isolation layer thickness,the amount of the enteric-coating anticaking agent and enteric-coating levels.The results showed that when the isolation layer thickness was 6%,the anticaking in the enteric coating accounted for 10%,and enteric-coating level was 10%,we found the three batches of self-made omeprazole enteric-coated tablets were of good quality and consistent with the dissolution behavior of the reference formulation.The self-made omeprazole enteric-coated tablets and commercial omeprazole enteric-coated tablets?reference preparations?were tested under the influence factors of high temperature,high humidity and light.The results showed that these two omeprazole enteric-coated tablets were more sensitive to humidity.The self-made preparations showed an increase dissolution behavior in the accelerated test for 3 months and 6 months compared with 0months.Long-term tests showed that the self-made omeprazole enteric-coated tablets had good stability for 6 months.In summary,the analysis method of omeprazole enteric-coated tablets is accurate,prescription technology is reliable and operability is strong.Compared with the reference preparations,the self-made omeprazole enteric-coated tablets have similar dissolution curves and stable properties,which lays a foundation for product development.