Manufacturing and characterization of long-acting levonorgestrel intrauterine systems.
Manufacturing and characterization of long-acting levonorgestrel intrauterine systems.
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DOI：
10.1016/j.ijpharm.2018.09.004
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发表时间：
2018-10-25
影响因子：
5.8
通讯作者：
Burgess DJ
中科院分区：
文献类型：
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作者：
Bao Q;Gu B;Price CF;Zou Y;Wang Y;Kozak D;Choi S;Burgess DJ
Mirena®是一种长效(5年)避孕宫内节育器。它由一个中空的圆柱形药物储存库(含有左旋诺孕酮和聚二甲基硅氧烷)组成，上面覆盖着一层控制释放速度的硅胶膜。这种结构对宫内节育器的制造提出了挑战，到目前为止，还没有关于这些中空圆柱形宫内节育器的制造、产品设计和质量评估的文献报道。为这些长效宫内节育器或系统开发一种可重复性和健壮的制造工艺，以了解此类药物-装置组合的体外和体内性能是至关重要的。在这项研究中，开发了一种定制模具的双注射器方法来制造基于聚二甲基硅氧烷(PDMS)的中空圆柱形左旋诺孕酮宫内系统(LNG-IUSS)。通过对不同模具材料、固化温度和固化时间的筛选，制备出具有良好质量特性(易脱模、外观美观、理化特性适宜)的PDMS-药物储存库。在制备的PDMS药物储存库上覆盖释放速率控制膜，制备了LNG-IUSS。对不同载药量(10%、25%和50%w/w)的PDMS药库进行了物化表征(药物含量和含量均匀度、粉末X射线衍射仪、差示扫描量热分析、热重分析和傅立叶变换红外光谱)。不同载药量的LNG-IUSS在37℃的生理盐水(0.9%w/v氯化钠)中用100rpm的水浴摇床进行实时体外释药试验。制备的PDMS-药物储存库表现出良好的和可重复性的质量特征，包括外观(表面光滑)、靶向载药量和PDMS基质中良好的药物含量均匀度。X射线衍射分析表明，API的结晶度在PDMS基质中保持不变。DSC、TGA和FTIR证实了药物和PDMS的结构，表明制备的LNG-IUSS中药物与PDMS骨架之间没有相互作用。不同载药量的LNG-IUS体外实时释药均符合零级释药动力学，药物释放速率(以日释药百分数计算)与载药量成反比。
Mirena® is long-acting (5 years) contraceptive intrauterine device. It is composed of a hollow cylindrical drug reservoir (containing Levonorgestrel and polydimethylsiloxane), which is covered with a release rate controlling silicone membrane. This structure presents a manufacturing challenge and to date, there have been no literature reports on the manufacturing, product design and quality evaluation of these hollow cylindrical intrauterine devices. It is vital to develop a reproducible and robust manufacturing process for these long-acting intrauterine devices or systems to obtain an understanding the in vitro and in vivo performance of such drug-device combinations. In this study, a twin-syringe method with a customized mold was developed to manufacture hollow cylindrical polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs). Different mold materials, curing temperatures and times were screened to fabricate PDMS-drug reservoirs with good quality characteristics (easy demolding, good appearance and appropriate physicochemical characteristics). The prepared PDMS-drug reservoirs were covered with the release rate controlling membrane to fabricate the LNG-IUSs. Physicochemical characterization (drug content and content uniformity, powder X-Ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR) of the PDMS-drug reservoirs with different drug loadings (10%, 25% and 50% w/w) was conducted. Real-time in vitro drug release testing of LNG-IUSs with different drug loading was performed in normal saline (0.9% w/v NaCl) at 37 °C using a water bath shaker rotating at 100 rpm. The prepared PDMS-drug reservoirs demonstrated good and reproducible quality characteristics including appearance (smooth surfaces), targeted drug loading and good drug content uniformity in the PDMS matrix. The PXRD showed that the crystallinity of the API was maintained inside the PDMS matrix. DSC, TGA and FTIR confirmed the structure of the drug and the PDMS, indicating no interaction between the drug and the PDMS matrix in the prepared LNG-IUSs. Real-time in vitro drug release from the LNG-IUSs with different drug loadings showed zero-order release kinetics, and the drug release rate (based on daily release percentage) was inversely proportional to the drug loading.
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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：
6.6
作者：
Nelson, Anita L.
通讯作者：
Nelson, Anita L.
影响因子：
4.2
作者：
Aliyar, Hyder;Schalau, Gerald, III
通讯作者：
Schalau, Gerald, III
影响因子：
158.5
作者：
Finer, Lawrence B.;Zolna, Mia R.
通讯作者：
Zolna, Mia R.
影响因子：
2.9
作者：
通讯作者：
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