当前位置:
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Direct NMR Monitoring of Phase Separation Behavior of Highly Supersaturated Nifedipine Solution Stabilized with Hypromellose Derivatives
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-05-30 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00178
Keisuke Ueda 1 , Kenjirou Higashi 1 , Kunikazu Moribe 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-05-30 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00178
Keisuke Ueda 1 , Kenjirou Higashi 1 , Kunikazu Moribe 1
Affiliation
![]() |
We investigated the phase separation behavior and maintenance mechanism of the supersaturated state of poorly water-soluble nifedipine (NIF) in hypromellose (HPMC) derivative solutions. Highly supersaturated NIF formed NIF-rich nanodroplets through phase separation from aqueous solution containing HPMC derivative. Dissolvable NIF concentration in the bulk water phase was limited by the phase separation of NIF from the aqueous solution. HPMC derivatives stabilized the NIF-rich nanodroplets and maintained the NIF supersaturation with phase-separated NIF for several hours. The size of the NIF-rich phase was different depending on the HPMC derivatives dissolved in aqueous solution, although the droplet size had no correlation with the time for which NIF supersaturation was maintained without NIF crystallization. HPMC acetate and HPMC acetate succinate (HPMC-AS) effectively maintained the NIF supersaturation containing phase-separated NIF compared with HPMC. Furthermore, HPMC-AS stabilized NIF supersaturation more effectively in acidic conditions. Solution 1H NMR measurements of NIF-supersaturated solution revealed that HPMC derivatives distributed into the NIF-rich phase during the phase separation of NIF from the aqueous solution. The hydrophobicity of HPMC derivative strongly affected its distribution into the NIF-rich phase. Moreover, the distribution of HPMC-AS into the NIF-rich phase was promoted at lower pH due to the lower aqueous solubility of HPMC-AS. The distribution of a large amount of HPMC derivatives into NIF-rich phase induced the strong inhibition of NIF crystallization from the NIF-rich phase. Polymer distribution into the drug-rich phase directly monitored by solution NMR technique can be a useful index for the stabilization efficiency of drug-supersaturated solution containing a drug-rich phase.
中文翻译:
直接NMR监测用羟丙甲纤维素衍生物稳定的高饱和硝苯地平溶液的相分离行为
我们研究了羟丙甲纤维素(HPMC)衍生物溶液中水溶性差的硝苯地平(NIF)的过饱和状态的相分离行为和维持机理。高过饱和的NIF通过与含有HPMC衍生物的水溶液进行相分离而形成了富NIF的纳米液滴。本体水相中可溶解的NIF浓度受到NIF与水溶液相分离的限制。HPMC衍生物可稳定富含NIF的纳米液滴,并通过相分离的NIF维持NIF过饱和数小时。富NIF相的大小根据溶解在水溶液中的HPMC衍生物而不同,尽管液滴大小与没有NIF结晶而保持NIF过饱和的时间没有关系。与HPMC相比,HPMC乙酸盐和HPMC琥珀酸乙酸盐(HPMC-AS)有效地保持了NIF过饱和,其中包含相分离的NIF。此外,HPMC-AS在酸性条件下可以更有效地稳定NIF过饱和。解决方案NIF过饱和溶液的1 H NMR测量表明,HPMC衍生物在NIF与水溶液的相分离过程中分布到富NIF相中。HPMC衍生物的疏水性强烈影响其向富NIF相的分布。而且,由于较低的HPMC-AS的水溶性,在较低的pH值下促进了HPMC-AS向富NIF相的分布。大量HPMC衍生物向富NIF相的分布诱导了从富NIF相强烈抑制NIF结晶。通过溶液NMR技术直接监测聚合物向富药相中的分布对于提高含有富药相的药物过饱和溶液的稳定效率可能是一个有用的指标。
更新日期:2017-06-28
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
直接NMR监测用羟丙甲纤维素衍生物稳定的高饱和硝苯地平溶液的相分离行为
我们研究了羟丙甲纤维素(HPMC)衍生物溶液中水溶性差的硝苯地平(NIF)的过饱和状态的相分离行为和维持机理。高过饱和的NIF通过与含有HPMC衍生物的水溶液进行相分离而形成了富NIF的纳米液滴。本体水相中可溶解的NIF浓度受到NIF与水溶液相分离的限制。HPMC衍生物可稳定富含NIF的纳米液滴,并通过相分离的NIF维持NIF过饱和数小时。富NIF相的大小根据溶解在水溶液中的HPMC衍生物而不同,尽管液滴大小与没有NIF结晶而保持NIF过饱和的时间没有关系。与HPMC相比,HPMC乙酸盐和HPMC琥珀酸乙酸盐(HPMC-AS)有效地保持了NIF过饱和,其中包含相分离的NIF。此外,HPMC-AS在酸性条件下可以更有效地稳定NIF过饱和。解决方案NIF过饱和溶液的1 H NMR测量表明,HPMC衍生物在NIF与水溶液的相分离过程中分布到富NIF相中。HPMC衍生物的疏水性强烈影响其向富NIF相的分布。而且,由于较低的HPMC-AS的水溶性,在较低的pH值下促进了HPMC-AS向富NIF相的分布。大量HPMC衍生物向富NIF相的分布诱导了从富NIF相强烈抑制NIF结晶。通过溶液NMR技术直接监测聚合物向富药相中的分布对于提高含有富药相的药物过饱和溶液的稳定效率可能是一个有用的指标。