Whole-process optimization for industrial production of glucosamine sulfate sodium chloride based on QbD concept

doi:10.1016/j.cjche.2022.03.025

Abstract

Abstract: The double salt of glucosamine sulfate sodium chloride (glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, let alone the optimization over the whole process to produce glucosamine-SP using glucosamine hydrochloride and anhydrous sodium sulfate as synthetic raw materials. In order to improve the production efficiency, this study screened the process parameters based on the concept of quality by design (QbD), optimized 13 operational parameters related to reaction and separation in the process, and finally proposed the mixed dropping process. The reaction conditions for the preparation of glucosamine-SP were found as follows: the molar ratio of anhydrous sodium sulfate to glucosamine hydrochloride is 0.42, the mass ratio of water to glucosamine hydrochloride is is 2.0, the reaction temperature is 50 ℃ and the reaction time is 1 h. Through step-by-step scaling up following QbD, the mixed dropping process was successfully applied to achieve a trial production of 200 kg products satisfying national quality standards. In all, the results of this study have high technical value and guiding significance for the industrial mass production of glucosamine-SP.

Key words: Glucosamine sulfate sodium chloride, Optimization, Quality by design (QbD), Production, Glucosamine hydrochloride, Sodium sulfate

摘要： The double salt of glucosamine sulfate sodium chloride (glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, let alone the optimization over the whole process to produce glucosamine-SP using glucosamine hydrochloride and anhydrous sodium sulfate as synthetic raw materials. In order to improve the production efficiency, this study screened the process parameters based on the concept of quality by design (QbD), optimized 13 operational parameters related to reaction and separation in the process, and finally proposed the mixed dropping process. The reaction conditions for the preparation of glucosamine-SP were found as follows: the molar ratio of anhydrous sodium sulfate to glucosamine hydrochloride is 0.42, the mass ratio of water to glucosamine hydrochloride is is 2.0, the reaction temperature is 50 ℃ and the reaction time is 1 h. Through step-by-step scaling up following QbD, the mixed dropping process was successfully applied to achieve a trial production of 200 kg products satisfying national quality standards. In all, the results of this study have high technical value and guiding significance for the industrial mass production of glucosamine-SP.

关键词: Glucosamine sulfate sodium chloride, Optimization, Quality by design (QbD), Production, Glucosamine hydrochloride, Sodium sulfate

Yingjun Lin. Whole-process optimization for industrial production of glucosamine sulfate sodium chloride based on QbD concept[J]. Chinese Journal of Chemical Engineering, 2023, 54(2): 153-161.

Yingjun Lin. Whole-process optimization for industrial production of glucosamine sulfate sodium chloride based on QbD concept[J]. 中国化学工程学报, 2023, 54(2): 153-161.

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