Cerciello Andrea, Auriemma Giulia, Del Gaudio Pasquale, Cantarini Marco, Aquino Rita P
a Department of Pharmacy , University of Salerno , Fisciano , SA , Italy ;
b PhD Program in Drug Discovery and Development , University of Salerno , Fisciano , SA , Italy ;
Drug Dev Ind Pharm. 2016 Dec;42(12):2063-2069. doi: 10.1080/03639045.2016.1195401. Epub 2016 Jun 14.
Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1-2 h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity.
In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release.
Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment.
Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DRcaps) a delivery platform has been developed to control KL release in a delayed (90 min lag time) and prolonged way (270 min complete release).
The platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.
赖氨匹林（KL）是治疗某些慢性炎症性疾病症状时最广泛使用的非甾体抗炎药之一。与布洛芬相比，KL具有更好的药代动力学和耐受性。然而，由于其1-2小时的半衰期较短，口服给药需要多剂量方案。因此，目前的工作是通过造粒将其包裹在水凝胶基体系中，以延长其活性。
在本文中，我们提出将海藻酸盐和果胶作为载体和释放调节剂，用于开发基于水凝胶的微丸，以实现KL的缓释和控释。
使用海藻酸盐或果胶通过Nisco Encapsulator®制备微丸。优化操作变量以制备具有所需形态和尺寸的微丸。通过扫描电子显微镜（SEM）和差示扫描量热法（DSC）分析固态性质。通过药典pH变化试验模拟胃肠道环境来研究药物释放性能。
造粒技术成功用于将高溶性药物如KL包裹在多糖基水凝胶中。果胶被证明是一种能够包裹赖氨匹林盐的合适聚合物。制剂（F8）显示出良好的形态性质和尺寸、高药物含量（15.6%）和包封效率（93.5%）以及良好的药物释放曲线。将F8置于耐酸胶囊（DRcaps）中，开发了一种给药平台，以延迟（90分钟滞后时间）和延长（270分钟完全释放）的方式控制KL的释放。
该平台可能被认为在受昼夜节律影响的慢性炎症性疾病中口服非甾体抗炎药方面具有潜在用途。
