Study On Preparation Process Of Hydroxypropyl-β-cyclodextrin In Injection

Hydroxypropyl-β-cyclodextrin(HP-β-CD) has been widely used as advanced pharmaceutical accessories upon which a variety of pharmaceutical developments are based due to its property as a medicinal carrier. Recently, because of the wide application of HP-β-CD as solubilizer for intravenous injection preparation, the safety of HP-β-CD has been paid more and more attention. Reducing the impurity content(β-cyclodextrin) and controlling the generation of the bacterial endotoxin in the producing process of injection grade HP-β-CD are becoming the most important issues.In this paper, experiments on the process optimization have been conducted regarding the existing in the actual production of HP-β-CD, process parameters such as the reaction temperature, reaction time have been refined. Investigation on the unit operations such as the ethanol desalination, the nanofiltration desalination and the dehydration have been carried out. By cleaning verification test, the cleaning procedure and cleaning standard operation procedure(SOP) of key equipments have been discussed. By statistics data of the actual production and experiment results, the conditions of resin changing have been analyzed. In order to guarantee the quality of product, the reaction temperature should be 28±2℃and the reaction time should be 4h±30min to ensure the product substitution degree in the range of 4.0 to 5.0. Under the optimized desalination and dehydration process condition, the average production yield has been raised 12.29%. The cleaning SOP of key equipments have been given and intermediate material storage time should be controlled within 24 h. The condition and the mass of resin changing have been determined. Under the optimized process condition, 5.76 RMB raw material cost and 8.12 RMB operation cost have been reduced for 1 kg product.