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Production of drug-delivery systems with Ibuprofen through encapsulation in nanofibers and -particles with core-shell architecture

机译:通过将布洛芬包裹在具有核-壳结构的纳米纤维和-颗粒中来生产药物递送系统

摘要

With the evolution of the high-trough-put screening (HTS) methods it is now possible to screen up to 100 000 pharmaceutical compounds each week and thus the amount of possible new active pharmaceutical ingredient (API) grow every week[1,2]. Because of the fact that nearly half of the new API found today with the help of HTS have a low water solubility, electrohydrodynamic atomization (EHDA) can help to encapsulate these drugs for better bioavailability[3,4].As model drug Ibuprofen was used in this thesis, because Ibuprofen is one of the most used non-steroidal anti-inflammatory drugs (NSAIDs) and has a low water solubility. To enhance the bioavailability of Ibuprofen an encapsulation of it into nanoparticles and -fibers with core-shell architecture was done and the encapsulation and releasing efficiency was investigated.Three different and already well researched polymers, poly( -caprolactone) (PCL), poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP), were used to encapsulate Ibuprofen into coaxial nanofibers.With PVA fibers a theoretical drug loading of 64 wt% was achieved and after 7 h 23% of the theoretical Ibuprofen amount was released, with a burst release of 20% after one hour.The PVP fibers could be loaded with 22 wt% of Ibuprofen and they released all of the, from the flow rates calculated, Ibuprofen after 20 h, so they showed a high encapsulation efficiency and a slow release rate, with only releasing 28% after one hour.With PCL as shell polymer two different types of coaxial fibers were produced, one with a core only made of Ibuprofen and the other with a PVP and Ibuprofen core. The first one released 100% of the theoretical Ibuprofen amount after 20 h with burst releases of 66% to 76% after one hour and drug loadings of 30 wt% to 50 wt% Ibuprofen into the fibers, in dependence of the PCL concentration used. The latter one had drug loadings of 19 wt% to 26 wt%, also in dependence of the used PCL concentration, and releases of 77% to 89% after 20 h and after one hour burst releases of 26% to 77% were achieved. With the PCL fibers and the PVP fibers one could achieve a covering of the therapeutic window of Ibuprofen over a time span of 8 h, in comparison to 2 h with commercially available tablets[5]. Furthermore with the combination of the fast releasing PVA fibers and the slowly releasing PCL one could also cover the therapeutic window from the first hour on.
机译:随着高通量筛选(HTS)方法的发展,现在每周可以筛选多达10万种药物,因此每周可能增加的新活性药物成分(API)的数量[1,2] 。由于事实上在HTS的帮助下发现的新API中有近一半具有低水溶性,因此电动流体雾化(EHDA)可以帮助封装这些药物以提高生物利用度[3,4]。使用模型药物布洛芬在本文中,由于布洛芬是最常用的非甾体类抗炎药(NSAIDs)之一,且水溶性低。为了提高布洛芬的生物利用度,已将其包封为具有核-壳结构的纳米粒子和-纤维,并研究了其包封和释放效率。三种不同且已经研究充分的聚合物,聚己内酯(PCL),聚(聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP)用于将布洛芬包封到同轴纳米纤维中.PVA纤维的理论载药量为64 wt%,7小时后布洛芬的理论量为23%释放后,一小时后突然释放20%.PVP纤维可以负载22 wt%的布洛芬,并且从计算出的流量来看,布洛芬在20小时后释放了所有的布洛芬,因此它们显示出很高的包封效率缓慢释放,一小时后仅释放28%。以PCL为壳聚合物,生产了两种不同类型的同轴纤维,一种具有仅由布洛芬制成的纤芯,另一种具有PVP和布洛芬的纤芯。第一个在20小时后释放理论布洛芬100%的量,一小时后爆发释放66%至76%,药物负载到纤维中的布洛芬浓度为30 wt%至50 wt%,具体取决于所用PCL浓度。后者也取决于所用的PCL浓度,其载药量为19 wt%至26 wt%,并且在20 h后和一小时后突释释放率为26%至77%,释放率为77%至89%。使用PCL纤维和PVP纤维,可以在8小时的时间内覆盖布洛芬的治疗窗,而使用市售片剂则需要2小时[5]。此外,结合快速释放的PVA纤维和缓慢释放的PCL,从头一个小时起,它也可以覆盖治疗范围。

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    Sigg Jérôme;

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  • 年度 2017
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  • 正文语种 en
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