| Objective:The aim of this study is to design and prepare gabapentin sustained-release tablets.When it was taken with food,the tablet swelled and stayed in the stomach,resulting in longer release of the active ingredient in the upper digestive tract.Therefore,its bioavailability was improved by this way.It is first generic drug of GRALISE?in China.Methods:1.Pre-formulation study:The crystalline form,particle size,hygroscopicity,pH solubility,leakage condition and stability of raw materials were studied.Its properties and quality were judged preliminarily.The quality profile,key quality attributes and prescriptions of the original formulation were analyzed as the study objective of the generic drug.2.Prescription study:Based on the prescription of GRALISE?,the preliminary risk assessment of the formulation variables was carried out on the particle size distribution of APIs,the type and dosage of sustained-release materials,adhesive dosage,lubricant dosage and coating weight gain.The prescription variables that greatly influenced on the critical quality attributes（Critical quality attributes,CQAs）of products were screened out.The release curve was used as the main evaluation index to screen the key prescription variables.3.Process optimization:Firstly,the preparation process was screened to determine the preliminary preparation production process.Then,the initial risk assessment was carried out on the main processes in the production process to screen out the variables that had a great influence on CQAs.The content uniformity,release,expansion size and tablet rigidity were taken as the main evaluation indexes to optimize the key process.4.Quality evaluation:Sample production was carried out by definite prescription process,and the reproducibility of prescription process was investigated.Comprehensive quality inspection of products and quality consistency evaluation with GRALISE?was carried out,and the influence factor was tested to compare the stability of the two products under the conditions of high temperature,high humidity and light.Results:1.The API used for prescription and preparation process development is consistent with the crystal form of reference preparation.The particle size of API has little effect on preparation quality.Gabapentin has little or no hygroscopicity and pH dependence.The raw materials have good stability,and the degradation under high temperature,high humidity and light conditions is similar to GRALISE?.2.After screening various types of sustained-release materials,the hydroxypropyl methylcellulose B and polyoxyethylene A were selected as the sustained-release materials.When the ratio of them was 1:1,the best sustained-release effect was obtained.The compressibility was improved by addition of 50 mg copolyvinone and 0.24%magnesium stearate to the prescription.It reduced the risk of sticking and picking.When weight gain range of coating is 2.0%-3.0%,the appearance of the preparation can be guaranteed without affecting the release rate.3.The direct pressing process can significantly improve the properties,fluidity and weight difference of materials.The main pressure is controlled in the range of 30 N～50 N,which can not only make the release rate meet the requirements,but also ensure the expansion size and tablet rigidity.This also meet the needs of the expansdable gastroretentive tablets.4.Three batches of samples were prepared according to the established prescription process.The difference between products was small,which was consistent with the quality of GRALISE（?）in vitro.The stability test showed that three batches of gabapentin sustained-release tablets had better stability,and the degradation degree was lower than that of GRALISE?.The results showed that the prescription and process of the three batches of gabapentin sustained-release tablets were better than GRALISE?in the stability.Conclusion:The preliminary quality comparison in vitro of a generic drug showed that it is more stable and suitable for scale-up. |
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