水溶性药物吸湿曲线拐点呈现的机制——“液膜”假说的探索  

Mechanism of the intrinsic mechanism of the inflection point-the exploration of a"liquid film"hypothesis

作　　者：熊妮 朱峻良 张雨婷 吴敏[1] XIONG Ni;ZHU Jun-liang;ZHANG Yu-ting;WU Min(School of Pharmacy,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院药学院,四川成都610500

出　　处：《药学学报》2025年第3期801-808,共8页Acta Pharmaceutica Sinica

基　　金：四川省医学科研课题(S20059);区域制剂中心联合科研基金项目(23LHZJ06);成都医学院-成都医学院第一附属中医医院临床科学研究基金项目(2022LHZYYB-04);国家级大学生创新创业训练计划项目(202313705017)。

摘　　要：临界相对湿度(critical relative humidity,CRH)是衡量固体药物吸湿性的重要指标,水溶性药物在CRH下吸湿激增的内在机制尚不完全清楚,作者对此展开了探索。首先,通过模型片剂吸湿法和传统的粉末吸湿法分别测定药物的CRH值,并确定两种方法的等效性,采用电导率仪检测不同相对湿度条件下药物模型片剂的电导率;然后,基于无水硫酸铜吸水后由灰白变蓝的特性,遂以之作为模型药物并测定其CRH值,将之压片后置于不同相对湿度条件下并拍照记录液膜的形成过程。综合电导率及颜色变化推测吸湿平衡曲线出现拐点的可能原因。结果测得蔗糖粉末和片剂的CRH分别为85.05%和85.01%,柠檬酸钠粉末和片剂的CRH分别为77.14%和76.93%,双侧t检验结果显示两种方法等效。柠檬酸钠在75%相对湿度条件下电导率变化较小,而在79%相对湿度条件下电导率突变,蔗糖与无水硫酸铜呈现出类似趋势。同时成功记录了无水硫酸铜在吸湿中蓝色从离散色点到连续的变化过程。综上,初步推测水溶性药物在CRH处吸湿剧增的机制可能是药物表面在吸湿过程中形成了一层连续“液膜”。The critical relative humidity(CRH)is an important indicator for measuring the hygroscopicity of solid drugs.The intrinsic mechanism of rapid moisture absorption of water-soluble drugs under CRH is not fully understood,and we conducted preliminary exploration on this topic.Firstly,the newly developed model tablet moisture absorption method and the traditional powder moisture absorption method were employed to determine the CRH values,an equivalence test between the two methods was conducted by a two-tailed t test.Then a conductivity meter was employed to measure the conductivity values of drug model tablets under different relative humidity(RH)conditions.As we know,anhydrous copper sulfate is a grayish white powder,which is easy to turn blue after absorbing water,based on this,this salt was selected as a model drug,and its CRH value was measured.Furthermore,anhydrous copper sulfate was compressed into tablets,then placed under different RH conditions.A series of photos were taken to record the formation process of the liquid film.The reason for the inflection point of the moisture absorption equilibrium curve was postulated based on changes in conductivity and color.The results showed that the CRH values of sucrose powders and tablets were 85.05%and 85.01%,respectively;and the CRH values of sodium citrate powders and tablets were 77.14%and 76.93%individually;the results of the two-tailed t test indicated that the two methods are equivalent.At RH of 75%,the conductivity of sodium citrate changed slightly,while at RH of 79%greater than the CRH,the conductivity underwent a sudden change.Sucrose and anhydrous copper sulfate showed a similar trend of change.In addition,the process of blue dots of anhydrous copper sulfate changing from discrete to continuous was successfully captured during the observation of moisture absorption.In summary,the aforementioned results suggest that the mechanism of the rising rapidly in moisture absorption curve of water-soluble drugs at CRH is probably attributed to the formation of a co

关 键 词：临界相对湿度 电导率 水溶性药物 吸湿平衡曲线 液膜 

分 类 号：R943[医药卫生—药剂学]