Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via G. Colombo 71, 20133 Milano, Italy.
Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Int J Pharm. 2019 Mar 25;559:280-288. doi: 10.1016/j.ijpharm.2019.01.046. Epub 2019 Jan 25.
An innovative delivery system for melatonin, based on the incorporation of solid lipid microparticles in orodispersible films (ODFs) made of maltodextrin, was designed and developed. Lipid microparticles at two different melatonin concentrations (10 and 20% w/w) were produced by the spray congealing technology using two different lipid carrier (tristearin and hydrogenated castor oil) and characterized in terms of size, solid state, drug loading and drug release pattern. Tristearin microparticles were discarded due to a polymorphic modification of the carrier. The incorporation of hydrogenated castor oil microparticles in ODFs by using the casting method did not alter significantly the shape and dimension of the microparticles and the mechanical properties (elasticity and strength) of the films, which remained acceptable for manufacturing and handling. The in vitro release studies performed in saliva, gastric and intestinal simulated media on ODFs containing melatonin loaded in hydrogenated castor oil microparticles revealed the possibility to combine with an immediate release of the drug and a sustained release over at least 5 h period. In conclusion, the proposed drug delivery system maintains the advantages of ODFs, i.e. the suitability to be swallowed without water, and permits the tuning of drug release according to the clinical needs by modulating the ratio of free and microencapsulated drug in the ODF.
设计并开发了基于将固体脂质微球包埋于麦芽糊精制成的口腔分散片（ODF）中的褪黑素新型传递系统。采用喷雾冷凝技术，使用两种不同的脂质载体（硬脂酸三酯和氢化蓖麻油），制备了两种不同褪黑素浓度（10%和 20%w/w）的脂质微球，并对其粒径、固体状态、载药量和药物释放模式进行了表征。由于载体的多晶型改性，硬脂酸三酯微球被废弃。通过浇铸法将氢化蓖麻油微球包埋于 ODF 中，并未显著改变微球的形状和尺寸以及薄膜的机械性能（弹性和强度），这些性能仍可接受用于制造和处理。在唾液、胃和肠模拟介质中进行的包含负载于氢化蓖麻油微球中的褪黑素的 ODF 的体外释放研究表明，有可能与药物的即刻释放和至少 5 小时的持续释放相结合。总之，所提出的药物传递系统保持了 ODF 的优势，即无需水即可吞咽的适用性，并通过调节 ODF 中游离药物和微囊化药物的比例来根据临床需求调整药物释放。
