Study On The Preparation Technology Of High-shear Wet Granulation Of Gliclazide Tablets

Objective: As a regular drug for the treatment of type 2 diabetes,gliclazide has a large proportion in the oral hypoglycemic market.In order to improve the quality of gliclazide and market competitiveness,it is critical to complete the consistent evaluation as soon as possible.In this study,generic tablets of gliclazide were prepared by high shear wet granulation process,and the amplification of the prescription and process was studied.Methods: In the analysis of reference listed drug,distinguishing dissolution condition was screened out.Characteristics of the particles were analyzed on the pre-screened prescriptions,especially more attentions were placed on the analysis of the factors affecting the dissolution of the tablets;Then,a combination of attribute-based and parametric-based scale-up strategies was designed in the light of laboratory-scale research,and solutions to problems emerged in the process were also obtained.Results: In the laboratory-scale research,it was found that there were differences in the content uniformity of gliclazide in particles with different sizes.The drug content lowered increased by the decrease of particle size;Disintegration and drug dissolution rate are the slowest when the particle size is >850 ?m;The amount of water had the greatest influence on the dissolution of the tablets,dissolution rate increased with higher amount of water in a certain range,otherwise it decreased when the amount of water exceeds a critical amount.The total mixing time and impeller speed possess a certain effect on the dissolution of the granules.When the total mixing time exceeds 5min,the dissolution rate of the granules significantly reduced,but does not significantly affect the dissolution rate in the later stage,and impeller speed exceeds 250r/min,the dissolution rate of the granules significantly reduced.In the scale of enlargement to 50,000 pieces,the problem of slower dissolution was solved by adjusting the amount of water,and other characteristics of the tablet were in line with expected standards.In the scale of enlargement to 400,000 pieces,API and knocking of tablets edge we confirmed the cause of failure friability and sticking,which was solved by the equipment debugging and processing parameters optimization,and the pilot products with qualified dissolution were successfully prepared.Conclusion: The design and scale-up of gliclazide high-shear wet granulation process is reasonable,pilot-scale products with expected dissolution were obtained through the development of equipment and process parameters,which provided a good reference for the development of generic gliclazide.