Study On The Preparation Of Trimetazidine Hydrochloride Sustained-release Tablets

Trimetazidine Hydrochloride Sustained-Release Tablets is a product developed in France.It is mainly used for the preventive treatment of angina pectoris in the earlier stage.This sustained-release dosage form can release the drug slowly and uniformly,reduce the number of medications for patients,and improve the patient’s compliance.This subject uses trimetazidine hydrochloride sustained-release tablets produced by servier as the reference preparation,and is based on the national drug standard YBH02462010 to conduct a study on the preparation of 35 mg tablets.A drug analyse method was established.The release determination was made by the small cup method,the volume of the dissolution medium was 150 m L,and the paddle speed was 50 r/min.The release of the sustained-release tablets was determined by ultraviolet spectrophotometry,and the detection wavelength of the drug release was determined to be 267 nm;Use high performance liquid chromatography to determine the content and related substances of sustained-release tablets,chromatographic column:octadecylsilane bonded silica gel as filler,4.6×250 mm,5 μm,UV detector: detection wavelength 210 nm,flow Phase: water-methanol-acetonitrile-sodium heptane sulfonate solution(60:40:10:3),column temperature: 30 ℃,flow rate: 1.0 m L/min,and verify the release and content detection method.Trimetazidine hydrochloride is a BCS Ⅲ drug with high solubility and low permeability.According to the properties of various excipients,determine the main types of excipients,the sustained-release matrix material hydroxypropyl methylcellulose K4 M,filler pregelatinized starch and microcrystalline cellulose PH102,glidant silicon dioxide,lubricant stearic acid Magnesium,Opadry coating powder.The compatibility of raw materials and excipients was studied,and the content of impurity4-(2,3,4-trimethoxybenzyl)-1-piperazine hydrochloride increased slightly after being placed for 10 days under three conditions of high temperature,light and high humidity.Which proves that the raw and auxiliary materials have good compatibility.Using the powder direct compression preparation process,the prescription is:HPMC 40.4 mg,pregelatinized starch and microcrystalline cellulose PH102 are 71 mg,50 mg,silicon dioxide 3.5 mg,and magnesium stearate 1.5 mg.First add the raw material medicine,hydroxypropyl methylcellulose K4 M,pregelatinized starch,and microcrystalline cellulose PH102 into the mixer for pre-mixing,and then add silicon dioxide and magnesium stearate for total mixing.The weight of the plain tablet is 0.2 g,use 20% Opadry coating powder aqueous solution to coat the plain tablets,and the coating gains 3%.The release,content and related substances of the small test samples were tested,and the results all met the standards.Carry out pilot scale-up(100,000 tablets scale),adjust the pre-mixing speed,tablet press speed,and coating pot speed on the basis of small-scale trials,and continuously carry out three batches of process verification production.The quality study of the self-made samples shows that the uniformity of the self-made samples is better.Stability studies were conducted on the verification batch of samples,and the release rate in phosphate buffer solution was within 33%～36% for 1 hour,within48%～52% for 2 hours,and within 88.0%～94% for 8 hours;No more than 0.2%,the maximum total impurities is 0.227%;the content is all above 99%.It shows that the self-made samples have good stability,and the research of this subject has reached expectations.