The Study On Consistency Evaluation Of The Quality For Generic Drug Of Montmorillonite Powder

Purpose: Montmorillonite powder,as the basic drug for the treatment of diarrhea,plays an important role in laxative drugs.Since the original development agent entered the Chinese market in 1992,more than 30 montmorillonite generic drugs have been approved for listing in China.In order to further standardize the generic drug market and meet the ICH requirements,the state opens the curtain on the consistency evaluation of generic drugs,requires generic drugs to be consistent with the reference drugs in active ingredients,specifications,dosage forms,route of administration and curative effect.Montmorillonite powder ranks among the first categories of varieties that need to complete consistency evaluation.Because montmorillonite powder is not absorbed into the blood and do not conform to the BCS classification,it can be exempted from BE,so we must reinforce the systematic,in-depth and comprehensive development in vitro pharmacy researches.Based on the above background,this paper establishes a systematic and complete evaluation method in vitro consistency,which mainly aims at the consistency evaluation of the quality for generic drug of montmorillonite powder,including the evaluation of prescriptions and processes,in-depth study of key quality attributes such as key efficacy parameters(granularity,adsorption,sedimentation behavior),impurity spectra(quartz and other impurities,asbestos,heavy metals and harmful elements).Methods: This paper determined the research direction by deciding the target product quality profile of reference preparation.The comparative study of prescription and technology was completed by conducting the compatibility test of raw materials,evaluating raw materials and excipients,using the concept of QbD to optimize generic drug process.This paper focused on the key quality attributes of generic drug and reference preparation,conducted in-depth comparative studies,including the contents of aluminum and magnesium were determined by ICP-MS method;The difference of particle size between reference preparation and generic drugs was evaluated by sieving method,malvern laser particle size method and sedimentation volume ratio method;The difference of adsorption force was evaluated by strychnine sulfate method,cobalt hexaammonium trihydrate method and determination of specific surface area of BET method;this paper studied the related impurities(quartz and other impurities,asbestos and 7 kinds of heavy metal elements)of montmorillonite powper,quartz and other impurities were evaluated by x-ray diffraction method,asbestos were studied by x-ray diffraction method and biological microscopy method,the release behavior of 7 kinds of heavy metal elements was evaluated by the pretreatment method of simulating metabolism in vivo and ICP-MS.Hence,the overall monitoring of impurity system was accomplished.This paper determined the quality standard of consistency evaluation,completed the comparative study of quality consistency between 3 batches of generic drugs and 3 batches of reference preparations,and investigated the stability of generic drugs and reference preparations by influencing factor test,accelerated test and long-term test.Results: 1)The test results are not basically significant changes when the raw materials and excipients are placed at high temperature,high humidity and high light for 0 days and 10 days.The dosage form and prescription composition of generic drugs and reference preparations are basically identical.It is speculated that the processes are also basically the same according to the research results of generic drug process,the consistent results of prescriptions,dosage forms and packaging materials for generic drugs and reference preparations.2)The contents of magnesium are slightly higher and the contents of aluminum are slightly lower in generic drugs as compare to reference preparation by ICP-MS method,which show that the APIs of generic drugs and reference preparations derive from different manufacturers.The particle size distribution of generic drugs is not concentrated enough,and the particle size is slightly larger than that of reference preparation by malvern laser particle size method.The results of sieving method and settlement volume ratio directly or indirectly reflect the consistency of the particle size for generic drug and reference preparation.The specific surface area of generic drugs is slightly variate from reference preparation by BET method,but the results of adsorption force are consistent by strychnine sulfate method and cobalt hexaammonium trihydrate method.The results of quartz and other impurities are lower than that of reference preparation,generic drugs are superior to reference preparation,which also indicate that the APIs come from different manufacturers.The results of asbestos are consistent for generic drugs and reference preparations,and asbestos are not detected.The results of 7 kinds of heavy metal elements show that lead,arsenic which the state requires a focus on are consistent,although the contents of the remaining impurity elements have difference,but they are far below the limit requirements,it is not required to control according to the ICH Q3 D guide.It is consider that the raw materials of generic drugs and reference preparations have selected different manufacturers.Montmorillonite is a kind of ore.The inherent properties of the different ores have some differences,which is not to be resolved by the processing of the preparation.So the differences of some results are acceptable.Finally,the results of the quality consistency between 3 batches of generic drugs and 3 batches of reference preparations and their stability results are also consistent.Conclusion: In summary,it can be concluded that the quality of generic drugs and reference preparations are basically the same,and generic drugs and reference preparations can achieve clinical substitution with each other.In general,the consistency evaluation is comprehensive and scientific,which can be used to systematically evaluate the consistency between generic drugs and reference preparations.It provides reference for the consistency evaluation of similar generic drugs.It is of great significance for standardizing the generic drug market.