Study On Production Process And Quality Evaluation System Of Roxithromycin Capsule Quality Consistency Evaluation

Objective: To implement NMPA on the matters related to the <<Opinions of the General Office of the State Council on the Evaluation of the Consistency Evaluation of the Quality and Efficacy of Generic Drugs>>,The research to the consistency evaluation of the company’s self-made Roxithromycin capsules and the Roxithromycin tablets produced by the Sanofi·Aventis company of French original research to enhance the efficacy and quality of domestic generic drugs.Therefore,According to the technical requirements for the consistency evaluation of drugs,with reference to the original research,the research to determine the quality evaluation of raw materials for self-made Roxithromycin capsules,the best formulation and production process,product quality standards and evaluation system,To improve generic product quality of the domestic Roxithromycin capsule and the overall level of domestic drug quality.Methods: The first part is analysis systematically the Roxithromycin capsule reference preparation of the Roxithromycin tablets which published by the state.The generic drug often uses reverse engineering ideas to conduct reverse research for the original research drug,and roughly understands the prescription composition,process means,and crystal form of the drug substance,finally make the self-made products with the same efficacy and quality as the reference preparation.Through the prescription research and process optimization of Roxithromycin capsules,and reasonable prescriptions and production process parameters suitable for commercial production of Pharmaceutical factory weredetermined.The second part uses HPLC to develop the in vitro dissolution method of Roxithromycin capsules and establishes the correlation study with the in vitro dissolution of the reference preparation Roxithromycin tablets;through reproducing the standards for determination of Roxithromycin capsules in different countries,the JP standard Reproducing the separation effect of the main peak is the best,so the content determination method is optimized on the JP standard,and the content limit of the Roxithromycin capsule is rationally formulated.At the same time,the self-product method of relative substance is also developed on the JP standard;Roxithromycin capsule consistency evaluation project is a modified type for the national reference preparation.In order not to affect its Bioavailability and dissolution,it also provides a basis for the treatment of API in subsequent formulation and formulation research.This article will control the particle size of Roxithromycin raw material.The third part is to study the three batches of products in the laboratory through the determined quality evaluation system of the self-made Roxithromycin capsules.The fourth part is to study the stability of the three batches of products in the laboratory through the determined quality evaluation system of the self-made Roxithromycin capsules.Results: The study determined the dissolution method,content determination method,related substance method,particle size of the drug substance in the formulation prescription,the formulation prescription of Roxithromycin capsule,production process parameters and production equipment.Conclusion: 1.Prescription composition Roxithromycin capsule is a modified variety of the original research drug R-oxithromycin tablets,the specification:150mg.Accessories are Low-substituted hydroxypropyl cellulose,Corn starch,Povidone K30,Poloxamer188,Colloidal silica,Magnesium stearate,gelatin hollow capsules.The prescription composition of the unit dose product is shown in Table 1.[Process operation]Raw material pretreatment: The raw material is passed through a 80 mesh sieve,and the colloidal silica is passed through a 40 mesh sieve for use;Material weighing: The raw materials of Roxithromycin,Low substituted hydroxypropyl cellulose and Corn starch are weighed according to the prescription amount;Preparation of adhesive: Dissolve povidone K30 and poloxamer in purified water with 65 ° C ~ 75 °C,stir until completely dissolved,and set aside;Premixing: The Roxithromycin,Low-substituted hydroxypropyl cellulose,Corn starch material is mixed into a wet granulator,the rotation speed is 300 rpm,and the mixing time is 5min;Wet granulation: Adding the prepared binder,stirring speed at 300 rpm,adding the adhesive to open the shear file,rotating at 1000 rpm,co-granulation time about 6 min,discharging,the granulation of 20 mesh sieve;Drying and granulating: Drying at 60 °C,moisture control at 2% to 4%,Shake the whole granulating pass through a 20 mesh sieve;Total mixing: Colloidal silica,Magnesium Stearate is weighed according to the prescription amount which mix with the above-obtained granules in a cylinder for 15 min,rotating at 20 rpm;Capsule filling: Capsule filling was carried out at a theoretical filling amount of 217.4 mg/particle.2.Traits Detection method: Visual method[24-25].Standard: The contents of the product are white or off-white powders and granules[24-25].3.Loading difference The weight difference limit is ±10%[24-25].4.Determination of content and related substances In combination with the 2015 edition of the Chinese Pharmacopoeia,Roxithromycin(C41H76N2O15)should be 98.0%-102.0% [24-25] of the content;the control of the related substances for Roxithromycin self-products is within a reasonable range.5.Roxithromycin raw material particle size range The raw material of drug passes through the 80 mesh sieve D10: controlled below 10 μm;D50: controlled at 20~40 μm;D90: controlled at 90~120 μm.