Imprvoing the solubility of Rivaroxaban via nanocrystallizion
详细信息 查看官网全文
- 英文论文题名：Imprvoing the solubility of Rivaroxaban via nanocrystallizion
- 论文作者：Jin-Mei Li ; Jia-Mei Chen ; Tong-Bu Lu
- 英文论文作者：Jin-Mei 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;
- 英文论文关键词：Nanocrystal ; Rivaroxaban ; Dissolution ; Bioavailability
- 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：1
- 文件大小：338k
- 原文格式：D
- 会议级别：全国
摘要
we described a Rivaroxaban(RIV) nanocrystal for overcoming poor solubility here. The results showed that using dissocubes method with polxamer 188、Hydroxy Propyl Methyl Cellulose(HPMC) E9 and Sodium Dodecyl Sulfonate(SDS) as stabilizers, mannitol as freeze-drying protective additive, RIV nanocrystal was produced quickly, the average size of nanocrystal was 186.6±10.0 nm and the zeta potential was 27.03±2.33 mV. The X-ray powder diffraction(XRPD) and differential scanning calorimetry(DSC) analysis verified that the crystalline state of RIV was not transformed after nanocrystallizion. In simulated intestinal fluid(pH 6.8) and simulated gastric fluid(pH 1.2), apparent solubility values of rivaroxaban both are higher than those of the physical mixture and rivaroxaban powder, indicating the solubility of rivaroxaban can be improved by nanocrystallization. It was stable for at least 1 month at 4℃. The pharmacokinetic test in rats indicated that the area under plasma concentration-time curve(AUC_(0→∞)) value of RIV nanosuspension(0.552 mg/L·h) was about 4.8-fold higher than that of RIV solution(0.113 mg/L·h). In summary, rivaroxaban nanocrystals are a potential oral delivery system to improve rivaroxaban's poor dissolution and its oral bioavailability.
we described a Rivaroxaban(RIV) nanocrystal for overcoming poor solubility here. The results showed that using dissocubes method with polxamer 188、Hydroxy Propyl Methyl Cellulose(HPMC) E9 and Sodium Dodecyl Sulfonate(SDS) as stabilizers, mannitol as freeze-drying protective additive, RIV nanocrystal was produced quickly, the average size of nanocrystal was 186.6±10.0 nm and the zeta potential was 27.03±2.33 mV. The X-ray powder diffraction(XRPD) and differential scanning calorimetry(DSC) analysis verified that the crystalline state of RIV was not transformed after nanocrystallizion. In simulated intestinal fluid(pH 6.8) and simulated gastric fluid(pH 1.2), apparent solubility values of rivaroxaban both are higher than those of the physical mixture and rivaroxaban powder, indicating the solubility of rivaroxaban can be improved by nanocrystallization. It was stable for at least 1 month at 4℃. The pharmacokinetic test in rats indicated that the area under plasma concentration-time curve(AUC_(0→∞)) value of RIV nanosuspension(0.552 mg/L·h) was about 4.8-fold higher than that of RIV solution(0.113 mg/L·h). In summary, rivaroxaban nanocrystals are a potential oral delivery system to improve rivaroxaban's poor dissolution and its oral bioavailability.
we described a Rivaroxaban(RIV) nanocrystal for overcoming poor solubility here. The results showed that using dissocubes method with polxamer 188、Hydroxy Propyl Methyl Cellulose(HPMC) E9 and Sodium Dodecyl Sulfonate(SDS) as stabilizers, mannitol as freeze-drying protective additive, RIV nanocrystal was produced quickly, the average size of nanocrystal was 186.6±10.0 nm and the zeta potential was 27.03±2.33 mV. The X-ray powder diffraction(XRPD) and differential scanning calorimetry(DSC) analysis verified that the crystalline state of RIV was not transformed after nanocrystallizion. In simulated intestinal fluid(pH 6.8) and simulated gastric fluid(pH 1.2), apparent solubility values of rivaroxaban both are higher than those of the physical mixture and rivaroxaban powder, indicating the solubility of rivaroxaban can be improved by nanocrystallization. It was stable for at least 1 month at 4℃. The pharmacokinetic test in rats indicated that the area under plasma concentration-time curve(AUC_(0→∞)) value of RIV nanosuspension(0.552 mg/L·h) was about 4.8-fold higher than that of RIV solution(0.113 mg/L·h). In summary, rivaroxaban nanocrystals are a potential oral delivery system to improve rivaroxaban's poor dissolution and its oral bioavailability.
引文