Effect of crosslinking on the physicochemical properties of polydimethylsiloxane-based levonorgestrel intrauterine systems.
Effect of crosslinking on the physicochemical properties of polydimethylsiloxane-based levonorgestrel intrauterine systems.
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DOI：
10.1016/j.ijpharm.2021.121192
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发表时间：
2021-11-20
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：
基于聚二甲基硅氧烷 (PDMS) 的左炔诺孕酮宫内节育系统 (LNG-IUS)，例如 Mirena®，是长效药物-器械组合产品，旨在释放 LNG，用于长达 6 年的避孕目的。 LNG-IUS 由一个空心圆柱形药物-PDMS 储库组成，该储库安装有聚乙烯框架，并覆盖有外层 PDMS 膜。 PDMS 是存在于基质和外膜中的控释赋形剂。 PDMS 交联程度是 LNG-IUS 制造中的一个关键参数，决定了弹性和机械强度（这是圆柱形储罐成型和脱模的关键参数）。此外，弹性和机械强度对于防止插入子宫腔期间变形也很重要。本研究的目的是调查 PDMS 交联对 LNG-IUS 物理化学性质的影响，并开发适当的测试方法来表征其机械强度。通过改变PDMS弹性体基质和交联剂的比例来制备具有不同交联度的配方。开发了一种新的溶剂溶胀和萃取方法来测定 PDMS 交联度。交联程度还通过 FTIR、拉曼、1H NMR、DSC、TGA 和动态机械分析进行表征。正如预期的那样，交联度较高的配方表现出较低的结晶度。有趣的是，与高结晶配方相比，低结晶配方表现出更高的 Tg 值和储能模量，这意味着交联是控制 LNG-IUS 物理化学和机械性能的主要参数。 PDMS 交联与 LNG-IUS 的理化性质之间建立了相关性，这将有助于配方筛选和开发过程中的质量控制。更好地了解这些复杂产品的理化特性将有助于药物产品的开发。
Polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs) such as Mirena® are long-acting drug-device combination products designed to release LNG for contraceptive purposes up to 6 years. LNG-IUSs consist of a hollow cylindrical drug-PDMS reservoir mounted with a polyethylene frame and covered by an outer PDMS membrane. PDMS is the release-controlling excipient present in both the matrix and the outer membrane. The degree of PDMS crosslinking is a key parameter in LNG-IUS manufacturing, dictating the elasticity and mechanical strength (which are critical parameters in molding and demolding of the cylindrical reservoirs). In addition, elasticity and mechanical strength are also important to prevent deformation during insertion into the uterine cavity. The objectives of this study were to investigate the impact of PDMS crosslinking on the physicochemical properties of LNG-IUSs and to develop appropriate testing methods for characterization of their mechanical strength. Formulations with different degrees of crosslinking were prepared by varying the ratio of the PDMS elastomer base and the crosslinking agent. A novel solvent swelling and extraction method was developed to determine the degree of PDMS crosslinking. The extent of crosslinking was also characterized via FTIR, Raman, 1H NMR, DSC, TGA and dynamic mechanical analysis. As expected, formulations with higher degrees of crosslinking showed lower crystallinity. Interestingly, the less crystalline formulations showed higher Tg values and storage moduli compared to the high crystalline formulations, implying that crosslinking is the predominant parameter governing the physicochemical and mechanical properties in LNG-IUSs. Correlations were established between PDMS crosslinking and the physicochemical properties of LNG-IUSs which will be useful for quality control purposes during formulation screening and development. A better understanding of the physicochemical characteristics of these complex products will facilitate drug product development.
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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
影响因子：
5.8
作者：
Bao Q;Zou Y;Wang Y;Choi S;Burgess DJ
通讯作者：
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作者：
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通讯作者：
RUEGGEBERG, FA
影响因子：
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作者：
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通讯作者：
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