合成龙脑制备片状冰片的结晶工艺研究

Crystallization process of synthetic schistose borneol

为解决传统合成龙脑结晶工艺效率低、周期长、产品成片率过低等缺陷,以120~#汽油作为结晶溶剂,考察投料配比(溶剂与合成龙脑质量比)、结晶温度、长晶空间、结晶时间对合成龙脑制备片状冰片的影响。结果表明:采用梯度降温、提高投料配比、拓展长晶空间及控制超溶解度点前后的降温速率等方法能有效促进晶体片状的形成。实验在结晶瓶中设置隔板,以投料比为1.6,结晶按饱和温度62.5℃至45℃速率0.5℃/h;45℃至35℃速率2℃/h;35℃至25℃速率3℃/h进行梯度降温,结晶时间6 d,所得冰片大小合适,成片率达100%,片状收率74.66%,产品经检测符合冰片质量标准(2010版中国药典)。改进的工艺对传统合成龙脑结晶产品的升级具有启示意义。

Conventional crystallization techniques of synthetic borneol show disadvantages of low efficiency,time consuming,low-yield,and so forth.Therefore,the effects of the mass ratio of solvent to crude borneol,crystallization temperature,and growth space and crystallization time on the formation of schistose borneol were studied using 120#gasoline as the crystallization solvent for optimal crystallization operation of synthetic borneol.The results indicate that the methods of gradient cooling,increasing feed ratio,enhancing growth-space and controlling the cooling rate before and after the super-dissolution point could effectively promote the formation of flaky crystals.The optimal crystallization setups are including reaction jar with partition plate,feeding ratio of 1.6∶1,and a unique cooling procedure that the saturation temperature initially decreases from 62.5℃to 45℃with a constant cooling rate of 0.5℃/h,then to 35.0℃with a cooling rate 2℃/h,and finally to 25℃with another cooling rate of 3℃/h and total operation time of 6 days,produce suitable dimensionality of schistose borneol,100%schistose production and the yield rate of 74.66%.The fabricated synthetic borneol meets the standard of borneol according to the 2010 edition of Chinese Pharmacopoeia.This study sheds new light into the upgrading of traditional production techniques of synthetic borneol.