| Objective:Study on the formulation of pramipexole hydrochloride gel matrix sustained-release tablets.A preliminary evaluation on the quality of the original preparation was carried out.Methods:1.The to establish a high performance liquid chromatography(HPLC)method for the determination of the content and the related substances of pramipexole hydrochloride,using powder properties tester determination of pramipexole hydrochloride powder characteristics,and to study the powder characteristics.2.HPLC method was used to establish pramipexole hydrochloride sustained release tablets in drug content and release rate in vitro determination method;in vitro release degree as the evaluation index,through the powder direct compression,wet granulation,dry granulation and other of preparation method,and the original research agents release curves were fitted to screen the prescription,and the formulation of reproducibility study,ultimately determine the preparation process.3.Three preparations of 3 batches of sustained-release tablets according to the selected prescription process,with the appearance,content,in vitro release of different media as the index,the original tablet as the reference,the quality of self-made tablets were evaluated.Results:1.In the 0.3790-3.0320μg·mL-1 concentration range,good linear relationship,standard curve equation for Y=4733.3X+108.69,R2=0.9999;instruments and RSD was 0.09%,sample reproducibility RSD is 1.30%;control products and tested in 24 hours and RSD was 0.94%and 0.045%,average recovery rate was 99.70%and RSD was 0.60%;related substances in the specificity test results show that,blank solvent did not interfere with the determination,the impurity and the main peak completely separated.The destructive test results show that the degradation products of various impurity peak damage of detection of the interference peak.Impurity a in the 0.4750to3.8000μg·mL-1 concentration range with good linear relationship,standard curve equation:Y=1 1.678X-0.7495,the correlation coefficient R2=0.9998.;B impurity in the 0.5000-4.000μg·mL-1 concentration range with good linear relationship for the linear equation:Y=7.5079X-0.5266,the correlation coefficient R2=0.9999.C impurity in the 0.4875-3.900μg·mL-1 concentration range with good linear relationship for the linear equation:Y=9.4241X-0.4479,the correlation coefficientR2=0.9999;impurity E in the 0.5125-4.100μg·mL-1 concentration range with good linear relationship for the linear equation:y=7.106X+0.0593.The correlation coefficient R2=0.9999.Impurity A,B,C,E of the limit concentration were 0.4750μg·mL-1,0.5000μg·mL-1,0.4875μg·mL-1,0.5125μg·mL-1,respectively.Impurity E,A,CK,B,C peak area of RSD were 1.2%,1%,2.8%,0.4%,0.9%,respectively.A impurity,the average recovery rate was 97.69%.RSD=3.86%;impurity B the average recovery rate was:96.0%,RSD=4.20%;impurity C the average recovery rate was:96.5%,RSD=3.71%;impurity e the average recovery rate was 94.6%.RSD=3.99%.The prepared solution was stable in 24 hours.Column temperature change between-2and2,pH change between-0.1and0.1,flow rate change+0.1,different chromatographic column on the determination of the related substances.Powder data show that the powder is good.2.The established HPLC method is used for the determination of pramipexole hydrochloride sustained-release tablets and in 3-30μg·mL-1 concentration range,good linear relationship,standard curve equation was y=28.412 x+0.3694,R2=1.0000;instruments and RSD was 2.72%,average recovery rate was 98.88%,and RSD was 1.15%.Refere the content determination method,the product release method for quantitative detection of also choose by HPLC.In 0.3-3μg·mL-1 concentration range,good linear relationship,standard curve equation was y=1015.7x+11.822,R2=0.9999;instruments and RSD 1.46%;and the average recovery rate was 97.72%,and RSD 2.67%;prescription screening results of dry granulation,formulation and dosage amount of pramipexole hydrochloride 0.75mg,pregelatinized starch dosage 183mg,dosage of HPMC-K15 237mg,amount of HPC is 75 mg silica 2mg,stearic acid magnesium 2.5mg.3 Hydrochloric acid pramipexole gel matrix sustained release tablets(150601,150602,150603)hardness were 72N,70N,73N,;friability were 0.055%and 0.048%and 0.046%;±5.5%,±4.6%,±3.7%respectively for the weight difference;150601 batch of sustained release tablets was 99.86%and RSD was 0.34%.150602 batch of sustained release tablets were 99.38%and RSD was 0.51%;150602 batch of sustained release tablets 99.88%RSD 0.51%.The similarity factor of the release curve of pH1.0 medium is 59,the similarity factor of the release curve under the pH6.8 medium is 71,and the similar factor of the release curve under the pH4.5 medium is 65.All indexes meet the requirements.Conclusion:HPLC method was used to determine the drug content and release rate,and the specificity and sensitivity were higher,and the content and release rate were satisfied.Homemade pramipexole hydrochloride gel matrix sustained release tablets prescription is reasonable,stable process,shows significant sustained-release effect in vitro,almost with the original research is consistent. |
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