Study On Aceclofenac Enteric-coated Pellets Capsules

Aceclofenac as a new and powerful non-steroidal drug,has significant effects in the treatment of osteoarthritis and rheumatoid arthritis.In 1992,Spain’s Prodesfrma company listed Aceclofenac tablets.Since non-steroidal anti-inflammatory drugs had an irritating effect on the stomach and may cause gastric bleeding,making these drugs into enteric-coated preparations can reduce the irritation.In this project,aceclofenac enteric-coated capsules（trade name:Fenkejing,specification 0.1 g）produced by Shanxi Kaiyuan Pharmaceutical Co Ltd were used as controlled drugs to prepare and study aceclofenac enteric-coated pellets capsules.The pre-prescription research was carried out to study the physicochemical properties of the API,and the types and limits of excipients were determined according to the prescription information of enteric-dissolved pellet.The compatibility test of the excipients was conducted.Under high temperature,high humidity and light conditions for10 days,there was no significant change in other impurities except diclofenac.Except for the increase in the degree,there is no obvious change in other impurities.The release rate of the control drug was determined by HPLC in p H 6.8 buffer.The chromatographic conditions were determined to be octadecyl bonded silica stationary phase（250×4.6 mm）,mobile phase:0.02 mol/L sodium dihydrogen phosphate（p H=7.0）:acetonitrile:methanol=50:30:20,detection wavelength:275 nm,flow rate:1.0 m L/min,injection volume:20μL.The subject carried out prescription screening,the type and dosage of adhesives,diluents and disintegrants in the drug loading layer,the type of blank pill core,the weight gain of the isolation layer and the enteric soluble layer were tested by single factor.The subject finally determined that the binder was 5%Hydroxylpropyl methyl E5 aqueous solution,the diluent ratio was 3:1 starch and microcrystalline cellulose,the disintegrating agent was the main dosage of 5%sodium carboxymethyl cellulose crosslinked,and the blank pill core was starch-microcrystalline cellulose.The weight of the isolation layer is increased by 5%and the weight of the coating is increased by 15%～22%.The release degree and related substances of self-made drugs were compared with control drugs.It was found that the f₂ similarity factor was all greater than 50,other single impurities were all less than 0.2%,and other total impurities were all less than 1.0%.The project carried out the optimization of the small test process（scale 4500 pellets）,investigated the main engine speed and material weight,powder feeding speed and spraying speed,investigated the drying temperature of isolated pellets,investigated the fluidization speed,atomization pressure,fluidization speed and spraying pump speed of enteric pellets,and investigated the drying conditions.The project finally determined the fluidized bed speed of the drug-loading pellet 140～350 r/min,the spraying speed 5～30r/min,and the powder feeding speed 10～60 r/min.The project determined the fluidized speed of the isolated pellet to be 1000～2000 r/min,and the fluidized speed of the enteric-soluble pellet to be 1500～2000 r/min.Atomization pressure is controlled at 0.20～0.25MPa.A high performance liquid chromatography method was established to determine the related substances,release and content of aceclofenac enteric-coated pellets capsules.The recovery rate experiment of 9 impurity reference substances was carried out,and the results were all in the range of 98.0%～102.0%,and the RSD of the recovery rate of 9samples was≤2.0%.The release degree of the filter membrane and speed factors were investigated,and it was found that the filter membrane had no effect on the filtration,and the dissolution speed was 100 revolutions.The subject verified the content method,and found out that the concentration of acetaclofenac was 0.01mg/m L,the limit of quantification was 2.664ng,and the recoveries of all methods were between 98.0%and102.0%.Carry out stability study,after influencing factor test,accelerated test and comparative study of related substances in long-term test,the content of aceclofenac is95.0%～105.0%of the labeled amount,and other total impurities are lower than the standard 0.4%and 1.0%,the release amount in the buffer is greater than 85%of the labeled amount.This subject has studied the dosage form of aceclofenac enteric-coated preparations,and the research results have reached expectations.