Impact of product design parameters on in vitro release from intrauterine systems.
Impact of product design parameters on in vitro release from intrauterine systems.
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DOI：
10.1016/j.ijpharm.2020.119135
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发表时间：
2020-03-30
影响因子：
5.8
通讯作者：
Burgess DJ
中科院分区：
文献类型：
--
作者：
Bao Q;Zou Y;Wang Y;Choi S;Burgess DJ
基于聚二甲基硅氧烷（PDMS）的左炔诺孕酮宫内节育器（LNG-IUSs）含有大量强效LNG，因此了解产品设计参数对体外和体内性能的影响非常重要，以确保安全性和有效性，并避免因剂量倾倒导致的严重副作用。LNG-IUS是一种复杂的药物-器械组合产品，其配方设计除了配方和工艺参数外，还需要考虑其他因素，如器械配置和尺寸。在本研究中，生产了10个定性（Q1）和定量（Q2）等同的LNG-IUS，但来源（供应商）和尺寸（即，外膜的厚度），药物颗粒大小，药物贮库的尺寸（即，内径）以及整个IUS的配置。开发了LNG-IUS的实时体外释放测试方法。此外，使用水-醇介质开发了加速释放检测方法，以减少与处方设计相关的时间。不同来源的LNG-IUSs和不同外膜厚度的LNG-IUSs对药物的体外释放有很大的影响。结果表明，外膜越厚，药物释放速率越慢。表征从不同来源获得的外膜的物理化学性质，以了解它们对LNG-IUS的体外药物释放的影响。组成和机械强度可能在药物释放的差异中起作用。用较大药物粒度制备的LNG-IUS制剂显示出略微较慢的日释放速率。组成相当的LNG-IUSs的药物释放速率与相应药物储库的表面积线性相关。影响药物释放速率的另一个因素是整个IUS的配置。结果表明，外膜的放置是重要的，即药物储存器的端部是否被覆盖。值得注意的是，在约900天的测试期间，实时释放显示出零级释放动力学。本研究全面了解了产品设计参数对LNG-IUS体外药物释放的影响。此外，开发的实时和加速放行检测方法对使用不同产品设计参数制备的组成等效的LNG-IUS显示出良好的区分能力。
Polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs) contain a large amount of potent LNG, and therefore it is important to understand the impact of product design parameters on the in vitro and in vivo performance to ensure safety and efficacy, as well as to avoid serious side effects resulting from dose dumping. LNG-IUS is a complex drug-device combination product, and its formulation design, requires consideration of additional factors such as device configuration and dimensions, in addition to formulation and processing parameters. In this study, ten qualitatively (Q1) and quantitatively (Q2) equivalent LNG-IUSs were manufactured with differences in source (supplier) and dimensions (i.e., thickness) of the outer membrane, drug particle size, dimensions of the drug reservoir (i.e., inner diameter), as well as configuration of the entire IUS. A real-time in vitro release testing method was developed for the LNG-IUSs. In addition, an accelerated release testing method was developed using hydro-alcoholic media in order to reduce the time associated with formulation design. Source variations and thickness of their outer membranes had a great impact on the in vitro drug release from the LNG-IUSs. It was demonstrated that the thicker the outer membrane, the slower the drug release rate. The physicochemical properties of the outer membranes obtained from different sources were characterized to understand their impact on the in vitro drug release of the LNG-IUSs. The composition and mechanical strength may play a role in differences in drug release. The LNG-IUS formulation prepared with the larger drug particle size showed a slightly slower daily release rate. The drug release rates from the compositionally equivalent LNG-IUSs linearly correlated to the surface area of the corresponding drug reservoirs. Another factor that affected the drug release rate was the configuration of the entire IUS. It was shown that the placement of the outer membrane was significant, i.e. whether the ends of the drug reservoir were covered or not. It is important to note that real-time release showed zero-order release kinetics over the test period of approximately 900 days. The current study provides a comprehensive understanding of the impact of product design parameters on the in vitro drug release of LNG-IUSs. In addition, the developed real-time and accelerated release testing methods showed good discriminatory ability for compositionally equivalent LNG-IUSs prepared using different product design parameters.
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影响因子：
2.1
作者：
Nelson AL;Massoudi N
通讯作者：
Massoudi N
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：
10.1163/156856206775997287
发表时间：
2006-01-01
影响因子：
3.6
作者：
Abbasi, F;Mirzadeh, H;Simjoo, M
通讯作者：
Simjoo, M
影响因子：
5.8
作者：
Bao, Quanying;Jog, Rajan;Burgess, Diane J.
通讯作者：
Burgess, Diane J.
影响因子：
158.5
作者：
Curtis, Kathryn M.;Peipert, Jeffrey F.
通讯作者：
Peipert, Jeffrey F.