Department of Pharmaceutical and Biomedical Sciences, University of Salerno, I-84084 Fisciano (SA), Italy.
Int J Pharm. 2011 Aug 30;415(1-2):196-205. doi: 10.1016/j.ijpharm.2011.05.077. Epub 2011 Jun 14.
In this study the feasibility of joining prilling and microwave (MW) assisted treatments as combined technique to produce controlled release alginate beads was tested. Beads were produced by prilling (laminar jet break-up) using different polymer concentrations and loaded with ketoprofen, a slightly soluble non-steroidal anti-inflammatory BCS class II drug characterized by low melting point. MW assisted treatments applied using different irradiating conditions were performed as drying/curing step. The effect of formulation conditions and process variables on drying kinetics, particle micromeritics, shape, surface and inner characteristics of the matrix as well as drug loading and drug release behaviour was studied (USP pH change method). The properties of MW dried particles were compared to those dehydrated by convective methods (room conditions and tray oven 105°C). Results showed that MW dried ketoprofen loaded beads were obtained in a very narrow dimensional range retaining shape and size distribution of the hydrates particles. Compared to the traditional drying methods, MW treatments were able to strongly increase drying rate of the hydrated beads achieving faster and controllable dehydration kinetics. Moreover, different regimes of irradiation affected structural properties of the particles such as matrix porosity as well as the solid state of the loaded drug. DSC, X-ray and FTIR analyses indicated complex chemical interactions between the drug and polymer matrix induced by MW, related with the regime of irradiation, that contributes to the differences in release profiles. In fact, MW treatments under different time and irradiating regimes are able to modulate drug release from alginate beads; high levels of irradiation led to beads suitable for immediate release oral dosage forms whereas the lowest regime of irradiation led to beads that achieved a prolonged/sustained release of the drug till 8h in simulated intestinal medium. This study showed that prilling in combination with microwave treatments is a useful and simple tandem technique to prepare dextran-based dried beads.
在这项研究中，测试了将造粒和微波（MW）辅助处理相结合作为一种联合技术来生产控释海藻酸钠珠的可行性。使用不同的聚合物浓度通过造粒（层流射流破裂）生产珠，并负载酮洛芬，酮洛芬是一种略有可溶性的非甾体抗炎药 BCS 类 II 药物，其特征为低熔点。MW 辅助处理应用于不同的辐照条件下作为干燥/固化步骤。研究了制剂条件和工艺变量对干燥动力学、颗粒微尺度、形状、基质的表面和内部特性以及药物负载和药物释放行为的影响（USP pH 变化法）。将 MW 干燥颗粒的性质与通过对流方法（室温条件和托盘烘箱 105°C）干燥的颗粒进行比较。结果表明，MW 干燥的负载酮洛芬珠可以在非常窄的尺寸范围内获得，保留水合粒子的形状和尺寸分布。与传统干燥方法相比，MW 处理能够强烈提高水合珠的干燥速率，实现更快和可控的脱水动力学。此外，不同的辐照制度影响颗粒的结构特性，如基质孔隙率以及负载药物的固体状态。DSC、X 射线和 FTIR 分析表明，MW 诱导药物与聚合物基质之间存在复杂的化学相互作用，与辐照制度有关，这导致了释放曲线的差异。事实上，MW 处理在不同的时间和辐照制度下能够调节海藻酸钠珠中药物的释放；高强度的辐照导致适合即时释放口服剂型的珠，而最低辐照制度导致珠能够在模拟肠液中持续释放药物 8 小时。本研究表明，造粒与微波处理相结合是一种有用且简单的串联技术，可用于制备基于葡聚糖的干燥珠。
