Screening and optimization of the formulation of human recombinant neutrophil inhibitory factor and hirulog hybrid for injection / 中国生物制品学杂志

ABSTRACT

@#Objective To screen and optimize the formulation and technology of human recombinant neutrophil inhibitory factor and hirulog hybrid(TNHH)for injection,and investigate its stability.Methods Based on the results of the single factor experiment,with the pH range,mannitol dosage and povidone K30 dosage as independent variables,and the content of high molecular protein as response value,the response surface design(CCF)test was used to analyze the effects of the respective variables and their interaction on the content of high molecular protein in TNHH for injection to screen out the optimal formulation. In order to facilitate the operation,the optimal formulation was adjusted to prepare three batches of samples in pilot scale,which were placed at 40 ℃,75% relative humidity(RH)for 2,4 weeks and 2 ～ 8 ℃ for 3,6 months,respectively. The samples were taken and the appearance,pH,purity of reversed phase-high performance liquid chromatography(RP-HPLC)and purity of size exclusion chromatography-high performance liquid chromatography(SECHPLC)were detected to verify the stability of this formulation and process.Results The optimal formulation was pH 4. 982 6,mannitol 7. 986 4% and povidone K30 1. 902 7%,which was finally adjusted to pH 5. 0,mannitol 8. 0% and povidone K302. 0%. The TNHH preparation for injection prepared by the optimized prescription and process were stable in quality and met the clinical medication requirements.Conclusion The optimum formulation of TNHH preparation for injection is reasonable in the process and suitable for industrial production.