| Purpose: Choose Plavix as a reference preparation,and determine the self-developed specification to be 75 mg(calculated as clopidogrel),and the dosage form is a tablet.Establish analytical methods,investigate the composition and preparation process of the prescription,and draw up a reasonable prescription process.Get the product consistent with the reference quality.Methods: 1.Refer to the pharmacopoeias of various countries to establish methods for the determination of related substances,enantiomers,content,and dissolution.2.Investigate the particle size,crystal form,solubility,hygroscopicity,compatibility of the bulk drug and excipients,and master the application and properties of the excipients.3.Conduct a reverse study on the reference preparation,draw up the initial formulation process,and investigate the amount of excipients and granulation methods.In the product preparation process,the characteristics of particle fluidity,tablet properties,material compressibility and dissolution curve are used as evaluation indicators,and compared with reference preparations,the formulation process with reasonable composition and good reproducibility is screened out.4.Investigate the parameters of granulation,total mixing,tableting and coating to determine the final production process parameters.Results: 1.An analysis method for the in vitro evaluation of this product has been established and the analysis method has been verified,and the method is good.2.Investigating the raw materials,it is found that the raw materials are pH-dependent,low-solubility drugs,almost non-hygroscopic,and the crystal form of the raw materials is II crystal form.Refer to the original research instructions to screen the amount of excipients.Using the dissolution results as the evaluation index,it is determined that the PH112 of microcrystalline cellulose is 31 mg/tablet,the mannitol is 68.925 mg/tablet,the polyethylene glycol 6000 is 34 mg/tablet,and the hydrogenated castor oil is 3.3 mg/tablet,low-substituted hydroxypropyl cellulose 12.9mg/tablet,both have good compatibility with APIs.Considering the feasibility of the process and the reasons for the yield of the raw material after sieving,the hot melt granulation method is finally selected,and the raw material only needs to pass through a 40-mesh sieve to meet the requirements.3.Taking the dissolution behavior and related substances as the inspection indicators,the production process parameters are screened,and the final customized pellet temperature is 70 ℃,and the pelletizing time is 180 s ~ 300 s.The total mixing time is 15 minutes,the relative humidity of the production workshop is 45% ~ 65%,the tablet hardness range is 80 N~110 N,the coating temperature is 50 ℃ ~ 60 ℃,and the weight gain is 2% ~ 3%.4.The relevant substances and enantiomers of the three batches of self-made drugs are all less than 0.5%,and the contents are all within 93.5% ~ 105.0% of the labeled amount,which all meet the requirements.The F2 factor of the self-made product and the reference is greater than 50 at p H 2.0 and aqueous medium.In the p H 6.8 and p H 4.5medium,the dissolution is incomplete as the reference,and the dissolution behavior is similar to that of the reference preparation,indicating the quality of the self-developed product Not less than the reference preparation.Conclusion: The prescription and production process of the self-made product are qualified,and the quality meets the quality standard of clopidogrel bisulfate tablets.Combining the above prescription process,a product with the same quality as the reference is obtained. |
PDF Full Text Request