Department of Pharmacy-Pharmaceutical Sciences, University of Bari "Aldo Moro", Bari, Italy.
Formulation and Application Services, Evonik Nutrition & Care GmbH, Darmstadt, Germany.
Int J Pharm. 2020 Jan 25;574:118922. doi: 10.1016/j.ijpharm.2019.118922. Epub 2019 Dec 10.
The purpose of this study was to develop a new solid paediatric formulation for propranolol hydrochloride (PR). This drug is used to treat various paediatric diseases, and recently received clearance to treat haemangioma. However, PR has a bitter salty taste that does not facilitate high rates of compliance among children, especially in liquid formulations. In addition, the solid formulations are designed for adults and often their dosage is not suitable for children that require a flexible dose based on their weight. Therefore, matrix microbeads of EUDRAGIT® E PO containing PR were manufactured to overcome these limitations. Nine different samples were prepared using the prilling-congealing technique with high yield. Using 2 nozzles, 300 and 450 μm (code n), the diameters obtained of microbeads (from 333 to 699 μm) were homogenous and appropriate to be swallowed by children. In this study, the ratio drug:matrix for the microbeads was also examined in detail: 1:25 (F), 1:15 (F) and 1:10 (F) in aqueous and tert-butyl alcohol/aqueous (code t) media. Most of the examined microbeads were characterized by high percentage of encapsulation efficiency (22-100%) and drug loading (22-77 mg of drug per g of matrix) effective for the administration of low and high doses of PR. SEM analysis revealed a matrix with a radial or a spongy structure, with numerous pores that generated soft floating microbeads in aqueous solution. Release studies confirmed a low release and dissolution of the drug in artificial saliva, mainly F > F > F, and a prompt dissolution in simulated gastric media. Finally, electronic tongue measurements revealed the ability of these formulations to mask the bitter drug taste, especially for the sample with a ratio 1:25 (F and F). These samples were chemically and physically stable for six months. In conclusion, the projected microbeads F, and F reached the goal of the study, and could be proposed as new solid oral formulations dedicated to use by children.
本研究旨在开发盐酸普萘洛尔（PR）的新固体制剂。该药物用于治疗各种儿科疾病，最近已获准用于治疗血管瘤。然而，PR 具有苦涩的味道，不利于儿童的高依从性，特别是在液体制剂中。此外，固体制剂是为成人设计的，其剂量通常不适合需要根据体重灵活调整剂量的儿童。因此，采用 EUDRAGIT® E PO 基质微球来克服这些局限性。使用制粒-凝固技术制备了 9 种不同的 PR 载药微球，产率高。使用 2 个喷嘴，300μm 和 450μm（代码 n），得到的微球直径（333μm-699μm）均匀，适合儿童吞咽。在这项研究中，还详细研究了微球中药物：基质的比例：水相和叔丁醇/水相（代码 t）中的 1:25（F）、1:15（F）和 1:10（F）。大多数研究的微球的包封效率（22-100%）和载药量（每克基质 22-77mg 药物）都很高，可用于低剂量和高剂量 PR 的给药。SEM 分析显示，基质具有放射状或海绵状结构，有许多孔，在水溶液中产生柔软的漂浮微球。释放研究证实，在人工唾液中药物释放和溶解缓慢，主要是 F>F>F，在模拟胃液中迅速溶解。最后，电子舌测量结果表明，这些制剂能够掩盖药物的苦味，特别是对于比例为 1:25（F 和 F）的样品。这些样品在六个月内化学和物理性质稳定。总之，预期的微球 F 和 F 达到了研究的目标，可以作为新的固体制剂用于儿童。
