Impact of polymer crosslinking on release mechanisms from long-acting levonorgestrel intrauterine systems.
Impact of polymer crosslinking on release mechanisms from long-acting levonorgestrel intrauterine systems.
复制标题
DOI：
10.1016/j.ijpharm.2021.121383
复制
发表时间：
2022-01-25
影响因子：
5.8
通讯作者：
Burgess, Diane J.
中科院分区：
文献类型：
--
作者：
Fanse, Suraj;Bao, Quanying;Zou, Yuan;Wang, Yan;Burgess, Diane J.
关键词：
聚二甲基硅氧烷(PDMS)的交联密度是左旋诺孕酮宫内系统(LNG-IUSS)的关键材料属性，它影响药物的释放，并可能对产品的性能和安全性产生重大影响。因此，本工作的目的是研究PDMS交联对LNG-IUS释放机制的影响，从而更好地了解产品。为了考察PDMS的交联效果，制备了不同预聚体比例和不同混合条件的LNG-IUSS。体外加速释放和实时释放LNG-IUS的时间分别为80天和7个月。与传统的理解相反，具有较高交联度的制剂显示出更快的药物释放速率。为了进一步了解这种异常的释放行为，我们研究了其微观结构和分子性质(使用扫描电子显微镜、压汞渗透仪、聚合物溶胀研究、固态硅核磁共振和广角X射线衍射)。有趣的是，高PDMS交联度形成了具有无定形聚合物结构域的固态多孔支化网络，便于(在有机溶剂中)快速吸收溶剂，并容易接触到药物颗粒，从而导致药物分子的快速传质。此外，与人工混合相比，行星混合制剂显示出更高的交联度和更快的药物释放速率。用一阶、两相(零阶+Higuchi)和Korsmeyer-Peppas模型对所有LNG-IUS进行了模型拟合。LNG-IUS的药物释放速率与PDMS的交联度之间采用一级模型(符合完全释放曲线)进行关联。这是第一份全面的报告，提供了对交联剂引起的微观结构变化和决定药物从LNG-IUS释放的物理化学性质的新见解。
Polydimethylsiloxane (PDMS) crosslinking density is a critical material attribute of levonorgestrel intrauterine systems (LNG-IUSs) that affects drug release and may have a significant influence on product performance and safety. Accordingly, the objective of the present work was to investigate the impact of PDMS crosslinking on the release mechanisms of LNG-IUSs and thereby achieve better product understanding. To investigate the effect of PDMS crosslinking, LNG-IUSs with varying prepolymer ratios and different mixing conditions were prepared. Accelerated and real-time in vitro release of the LNG-IUSs were conducted for up to 80 days and 7 months, respectively. Contrary to conventional understanding, formulations with higher crosslinking density showed faster drug release rates. To further understand this anomalous release behavior, the microstructure and molecular properties (using scanning electron microscopy, mercury intrusion porosimetry, polymer swelling studies, solid-state silicon NMR, and wide-angle X-ray diffraction) were investigated. Interestingly, it was revealed that high PDMS crosslinking forms a solid-state porous branched network with amorphous polymer domains facilitating fast solvent uptake (in organic solvents) and easy access to the drug particles leading to rapid mass transport of the drug molecules. Furthermore, formulations processed using planetary mixing showed higher crosslinking densities and faster drug release rates than those prepared using manual mixing. Model fitting of all LNG-IUSs were carried out using first order, two-phase (zero order plus Higuchi), and Korsmeyer-Peppas models. The first order model (which showed the best fitting for the full release profile) was used to establish correlations between the drug release rates and the PDMS crosslinking densities of LNG-IUSs. This is the first comprehensive report providing novel insights into crosslinking-induced microstructural changes and physicochemical properties that dictate drug release from LNG-IUSs.
登录
查看更多内容
影响因子：
5.8
作者：
Bao Q;Gu B;Price CF;Zou Y;Wang Y;Kozak D;Choi S;Burgess DJ
通讯作者：
Burgess DJ
DOI：
10.1002/polb.1986.090240602
发表时间：
1986-06-01
影响因子：
--
作者：
BESHAH, K;MARK, JE;HIMSTEDT, A
通讯作者：
HIMSTEDT, A
影响因子：
9.7
作者：
Martinez, Adam W.;Caves, Jeffrey M.;Ravi, Swathi;Li, Wehnsheng;Chaikof, Elliot L.
通讯作者：
Chaikof, Elliot L.
DOI：
10.1016/j.jconrel.2011.07.036
发表时间：
2011-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Teng W;Cappello J;Wu X
通讯作者：
Wu X
影响因子：
3
作者：
PEPPAS, NA;MERRILL, EW
通讯作者：
MERRILL, EW