Del Gaudio Pasquale, Auriemma Giulia, Russo Paola, Mencherini Teresa, Campiglia Pietro, Stigliani Mariateresa, Aquino Rita Patrizia
Department of Pharmacy, University of Salerno, Fisciano, Italy.
Department of Pharmacy, University of Salerno, Fisciano, Italy.
Eur J Pharm Biopharm. 2014 Aug;87(3):541-7. doi: 10.1016/j.ejpb.2014.02.010. Epub 2014 Feb 26.
In this study, biocompatible double layered beads consisting of pectin core and alginate shell were prepared through a single step manufacturing process based on prilling apparatus equipped with co-axial nozzles. The core was loaded with piroxicam (PRX) as model non-steroidal anti-inflammatory drug (NSAID). Morphology, size distribution and shape of the double layered beads varied depending on the operative conditions and polymer concentrations. Co-axial nozzles size, applied vibration frequency, gelling conditions and, mainly, polymers mass ratio were identified as critical variables. Particularly, the relative viscosity of polymeric feed solutions inside the nozzle was the key parameter to obtain homogeneous and well-formed coated particles. The produced beads were investigated for the release kinetic in different media. Once PRX was encapsulated within the pectin core, a controlled release pattern was observed. Particularly, beads produced with 4:1 core/shell ratio (F4) released less than 30% of PRX in simulated gastric fluid (SGF) while total liberation of the drug was achieved during the next 3h in simulated intestinal fluid (SIF). More interesting, F4 tested in SIF was able to release drug in a delayed and sustained manner at established time points (2h_8.2%, 3h_32.2%, 4h_70.1% and 5h_about 100%). Based on the above results, co-axial prilling approach is expected to provide success in manufacturing systems with delayed drug release profiles. Such systems may be potentially useful in targeting diseases which are affected by the circadian rhythm, such as chronic inflammation.
在本研究中,基于配备同轴喷嘴的造粒装置,通过一步制造工艺制备了由果胶核和藻酸盐壳组成的生物相容性双层珠粒。以吡罗昔康(PRX)作为模型非甾体抗炎药(NSAID)负载于核中。双层珠粒的形态、尺寸分布和形状随操作条件和聚合物浓度而变化。同轴喷嘴尺寸、施加的振动频率、胶凝条件以及主要的聚合物质量比被确定为关键变量。特别地,喷嘴内聚合物进料溶液的相对粘度是获得均匀且形状良好的包衣颗粒的关键参数。对所制备的珠粒在不同介质中的释放动力学进行了研究。一旦PRX被包裹在果胶核内,就观察到了控释模式。特别地,核/壳比为4:1(F4)制备的珠粒在模拟胃液(SGF)中释放的PRX不到30%,而在接下来的3小时内在模拟肠液(SIF)中药物实现了完全释放。更有趣的是,在SIF中测试的F4能够在既定时间点以延迟和持续的方式释放药物(2小时_8.2%,3小时_32.2%,4小时_70.1%,5小时_约100%)。基于上述结果,预计同轴造粒方法在制造具有延迟药物释放曲线的系统中会取得成功。这样的系统可能在靶向受昼夜节律影响的疾病(如慢性炎症)方面具有潜在用途。