Betulin(BE)has exceedingly become a potential natural product,providing multiple pharmacological and biological activi-ties,including anti-cancer,anti-viral,and anti-inflammatory benefits.Previous research indicated t...Betulin(BE)has exceedingly become a potential natural product,providing multiple pharmacological and biological activi-ties,including anti-cancer,anti-viral,and anti-inflammatory benefits.Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents.This property of BE can directly affect its extraction,isolation,and preparation process.In this study,a system of thermogravimetry(TG)-differential thermal analysis(DTA)coupled with mass spectrometry(MS)with electron ionization(EI)and photoionization(PI)capability,equipped with the skimmer-type interface(i.e.,skimmer-type interfaced TG-DTA-EI/PI-MS system),as a real-time and onsite analysis technique,was employed.Then,four solvatomorphs of BE,namely,with pyridine and water(A),sec-butanol(B),n,n-dimethylformamide(DMF)(C),and isopropanol(V),were analyzed for the first time.Finally,five kinds of the main volatile gaseous species,including H2O,pyridine,sec-butanol,DMF,and isopropanol,were identified clearly.Furthermore,the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time.This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products.展开更多
Voriconazole(VZL)is a second-generation and broad-spectrum triazole against fungal infections.Being a BCS(biopharmaceutics classification system)class II compound,the poor aqueous solubility has limited its bioavailab...Voriconazole(VZL)is a second-generation and broad-spectrum triazole against fungal infections.Being a BCS(biopharmaceutics classification system)class II compound,the poor aqueous solubility has limited its bioavailability and clinical efficacy.Aims to overcome this disadvantage,a cocrystallization strategy based on crystal engineering principles has resulted in five new multi-component crystals of VZL with maleic acid,L-tartaric,protocatechuic,gallic,and 3,5-dinitrobenzoic acids.Structure analysis revealed that the hydroxyl/carboxylic acid···triazole N_(3)hydrogen bonding interaction appears as a main supramolecular heterosynthon in the VZL multi-component crystals with organic acids.And VZL molecule has a flexible conformation in each of the five multi-component structures.The newly synthesized multi-component crystals showed impressive solubility improvement compared to that of the raw material of VZL.Molecular electrostatic potential surfaces(MEPS)analysis based on density functional(DFT)calculations revealed that hydrogen bond interactions in cocrystals mainly involved pairwise interactions in the global maxima and minima sites,but this rule is not always followed.This study indicates the potential of cocrystals to improve the solubility and dissolution rate of VZL.展开更多
Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubi...Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib(IM). Two stable salts with malonic acid(S1) and citric acid(S5), one metastable salt with fumaric acid(S2), two unstable salts with citric acid(S3, S4) were obtained for the first time.Single crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry,and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts(S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and p H 6.8 buffer, respectively.展开更多
基金supported by National Key R&D Program of China(Grant No.2016YFC1000900)National Science and Technology Major Project of China(Grant Nos.2017ZX09101001003,2018ZX09711001-010)+1 种基金National Natural Science Foundation of China(NSFC)(Grant No.81703473)CAMS Innovation Fund for Medical Sciences(Grant No.2017-I2M-3-010).
文摘Betulin(BE)has exceedingly become a potential natural product,providing multiple pharmacological and biological activi-ties,including anti-cancer,anti-viral,and anti-inflammatory benefits.Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents.This property of BE can directly affect its extraction,isolation,and preparation process.In this study,a system of thermogravimetry(TG)-differential thermal analysis(DTA)coupled with mass spectrometry(MS)with electron ionization(EI)and photoionization(PI)capability,equipped with the skimmer-type interface(i.e.,skimmer-type interfaced TG-DTA-EI/PI-MS system),as a real-time and onsite analysis technique,was employed.Then,four solvatomorphs of BE,namely,with pyridine and water(A),sec-butanol(B),n,n-dimethylformamide(DMF)(C),and isopropanol(V),were analyzed for the first time.Finally,five kinds of the main volatile gaseous species,including H2O,pyridine,sec-butanol,DMF,and isopropanol,were identified clearly.Furthermore,the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time.This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products.
基金supported by Beijing Natural Science Foundation(No.7222261)Key R&D Program of Shan Dong Province(No.2021ZDSYS26)+2 种基金the Fundamental Research Funds for the Central Universities(No.2021-RW350-001)the Xinjiang Uygur Autonomous Region Innovation Environment Construction Special FundTechnology Innovation Base Construction Key Laboratory Open Project(No.2022D04016)。
文摘Voriconazole(VZL)is a second-generation and broad-spectrum triazole against fungal infections.Being a BCS(biopharmaceutics classification system)class II compound,the poor aqueous solubility has limited its bioavailability and clinical efficacy.Aims to overcome this disadvantage,a cocrystallization strategy based on crystal engineering principles has resulted in five new multi-component crystals of VZL with maleic acid,L-tartaric,protocatechuic,gallic,and 3,5-dinitrobenzoic acids.Structure analysis revealed that the hydroxyl/carboxylic acid···triazole N_(3)hydrogen bonding interaction appears as a main supramolecular heterosynthon in the VZL multi-component crystals with organic acids.And VZL molecule has a flexible conformation in each of the five multi-component structures.The newly synthesized multi-component crystals showed impressive solubility improvement compared to that of the raw material of VZL.Molecular electrostatic potential surfaces(MEPS)analysis based on density functional(DFT)calculations revealed that hydrogen bond interactions in cocrystals mainly involved pairwise interactions in the global maxima and minima sites,but this rule is not always followed.This study indicates the potential of cocrystals to improve the solubility and dissolution rate of VZL.
基金CAMS Innovation Fund for Medical Sciences(Nos. 2017-I2M-1–010, 2020-I2M-1–003)Key National Research and Development Program (No. 2016YFC1000901)+1 种基金Construction and Application of Technology Integration System for Efficient Identification of Natural/Effective Active Small Molecules (No.2018ZX09711001–001)National Science and Technology Major Project:Resource Library of Traditional Chinese Medicine Component (No. 2019ZX09735002) for the financial support。
文摘Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib(IM). Two stable salts with malonic acid(S1) and citric acid(S5), one metastable salt with fumaric acid(S2), two unstable salts with citric acid(S3, S4) were obtained for the first time.Single crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry,and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts(S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and p H 6.8 buffer, respectively.
