Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization
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- 英文论文题名：Improving the Membrane Permeability of 5-Fluorouracil via Cocrystallization
- 论文作者：Xia-Lin Dai ; Song Li ; Jia-Mei Chen ; Tong-Bu Lu
- 英文论文作者：Xia-Lin Dai ; Song Li ; Jia-Mei Chen ; Tong-Bu Lu ; School of Pharmaceutical Sciences ; Sun Yat-Sen University ; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry ; School of Chemistry and Chemical Engineering ; Sun Yat-Sen University
- 年：2016
- 作者机构：School of Pharmaceutical Sciences,Sun Yat-Sen University;MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University;
- 会议召开时间：2016-12-19
- 会议录名称：中国晶体学会第六届学术年会暨会员代表大会（第六届全国晶型药物研发技术学术研讨会）论文摘要集
- 英文会议录名称：Abstracts of the 6th Annual Conference of Chinese Crystallographic Society
- 语种：英文
- 分类号：R943
- 学会代码：ZGJY
- 会议名称：中国晶体学会第六届学术年会暨会员代表大会——第六届全国晶型药物研发技术学术研讨会
- 会议地点：中国广东广州
- 主办单位：中国晶体学会
- 学会名称：中国晶体学会
- 页数：2
- 文件大小：471k
- 原文格式：D
- 会议级别：全国
摘要
Pharmaceutical cocrystallization is proposed as a new method to enhance membrane permeability of a BCS class Ⅲ model drug, 5-fluorouracil(5FU). Three cocrystals of 5FU, 5FU/3-hydroxybenzoic acid(1), 5FU/4-aminobenzoic acid(2) and 5FU/cinnamic acid(3), were successfully synthesized by a slurry method or a liquid-assisted grinding process. Spectroscopic methods, thermal analysis, and X-ray diffraction were used to characterize these new forms. The permeability was studied using a Franz diffusion cell and silicone membrane. All of the cocrystals showed improved membrane permeability compared to free 5FU. The cumulative amount per unit area of permeated 5FU in the first ten hours for 1-3 were increased by 41%, 70% and 83%, and the steady penetrate rate of 1-3 were increased by 38%, 66% and 79% respectively, as compared to pure drug. Structure-permeability correlation study finds a link between intermolecular interactions and molecular packing in cocrystals and their permeability behavior and has important implications for use of cocrystallization approach to improve drugs' permeability in pharmaceutical field.
Pharmaceutical cocrystallization is proposed as a new method to enhance membrane permeability of a BCS class Ⅲ model drug, 5-fluorouracil(5FU). Three cocrystals of 5FU, 5FU/3-hydroxybenzoic acid(1), 5FU/4-aminobenzoic acid(2) and 5FU/cinnamic acid(3), were successfully synthesized by a slurry method or a liquid-assisted grinding process. Spectroscopic methods, thermal analysis, and X-ray diffraction were used to characterize these new forms. The permeability was studied using a Franz diffusion cell and silicone membrane. All of the cocrystals showed improved membrane permeability compared to free 5FU. The cumulative amount per unit area of permeated 5FU in the first ten hours for 1-3 were increased by 41%, 70% and 83%, and the steady penetrate rate of 1-3 were increased by 38%, 66% and 79% respectively, as compared to pure drug. Structure-permeability correlation study finds a link between intermolecular interactions and molecular packing in cocrystals and their permeability behavior and has important implications for use of cocrystallization approach to improve drugs' permeability in pharmaceutical field.
Pharmaceutical cocrystallization is proposed as a new method to enhance membrane permeability of a BCS class Ⅲ model drug, 5-fluorouracil(5FU). Three cocrystals of 5FU, 5FU/3-hydroxybenzoic acid(1), 5FU/4-aminobenzoic acid(2) and 5FU/cinnamic acid(3), were successfully synthesized by a slurry method or a liquid-assisted grinding process. Spectroscopic methods, thermal analysis, and X-ray diffraction were used to characterize these new forms. The permeability was studied using a Franz diffusion cell and silicone membrane. All of the cocrystals showed improved membrane permeability compared to free 5FU. The cumulative amount per unit area of permeated 5FU in the first ten hours for 1-3 were increased by 41%, 70% and 83%, and the steady penetrate rate of 1-3 were increased by 38%, 66% and 79% respectively, as compared to pure drug. Structure-permeability correlation study finds a link between intermolecular interactions and molecular packing in cocrystals and their permeability behavior and has important implications for use of cocrystallization approach to improve drugs' permeability in pharmaceutical field.
引文
[1]Yan,Y.,Chen,J.M.,Lu,T.B.Simultaneously enhancing the solubility and permeability of acyclovir by crystal engineering approach,Cryst Eng Comm,2013,15,6457-6460.
[2]Sanphui,P.,Devi,V.K..,Clara,D.,et al.Cocrystals of Hydrochlorothiazide:Solubility and diffusion/permeability enhancements through drug-coformer interactions,Mol.Pharmaceutics,2015,12,1615-1622.
[2]Sanphui,P.,Devi,V.K..,Clara,D.,et al.Cocrystals of Hydrochlorothiazide:Solubility and diffusion/permeability enhancements through drug-coformer interactions,Mol.Pharmaceutics,2015,12,1615-1622.