Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy, Szeged, Hungary.
Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy, Szeged, Hungary.
J Pharm Biomed Anal. 2018 Jan 30;148:73-79. doi: 10.1016/j.jpba.2017.09.019. Epub 2017 Sep 22.
Antibiotic delivery in form of dry powder inhalation has been studied for possible clinical treatment of respiratory tract infection in the recent years. Dry powder inhalation of ciprofloxacin hydrochloride (CIP) assures local antibacterial activity and comfort of easy application. The aim of this work was to test the stability of co-spray-dried CIP in carrier free system. Since the microparticles in the dry powder system are amorphous and do not contain any stabilizer, the effects of temperature and relative humidity (RH) on the physicochemical properties and aerosolization behavior are very important. Therefore investigation of the role of excipients (such as polyvinyl alcohol (PVA), l-leucine (LEU) and hydroxypropyl-beta-cyclodextrin (CD)) on physicochemical stability and aerosolization performance is essential element prior designing the final dosage form. Stability tests (stress and accelerated) were performed at 40±2°C and 75±5% RH during 6 months. Particle characterization and size measurement - as the most important parameters in aerodynamic behavior - were done by the laser diffraction method, the surface morphology of microparticles was evaluated by scanning electron microscopy (SEM). The physiochemical properties of microparticles were investigated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The resulting aerodynamic behavior of microparticles was studied by Andersen cascade impactor. The overall stability results (against RH and temperature) showed that microparticles containing CIP and LEU alone and in combination with the other excipients were more stable than those containing PVA or CD alone. In relation to fine particle fraction and mass median aerodynamic diameter (determining the aerosolization parameters), it was found that the particle size and particle shape did not show significant changes after the storage. Among the excipients LEU was found to have many advantages, including relatively simple formulation, enhanced aerosolization behaviour, convenient portability and inherently improved stability. Such a composition may serve as an innovative drug delivery system for the local treatment of respiratory tract infection and cystic fibrosis.
近年来，干粉吸入剂已被研究用于治疗呼吸道感染的临床治疗。盐酸环丙沙星（CIP）干粉吸入可确保局部抗菌活性和易于应用的舒适性。本工作的目的是测试无载体系统中共喷雾干燥的 CIP 的稳定性。由于干粉系统中的微粒是无定形的，并且不含有任何稳定剂，因此温度和相对湿度（RH）对物理化学性质和空气动力学行为的影响非常重要。因此，研究赋形剂（如聚乙烯醇（PVA）、L-亮氨酸（LEU）和羟丙基-β-环糊精（CD））对物理化学稳定性和空气动力学性能的影响是设计最终剂型的重要因素。在 40±2°C 和 75±5%RH 下进行了 6 个月的稳定性测试（应力和加速）。通过激光衍射法对微粒的粒径和粒径分布（空气动力学行为的最重要参数）进行了表征和测量，通过扫描电子显微镜（SEM）评估了微粒的表面形貌。通过 X 射线粉末衍射（XRPD）和差示扫描量热法（DSC）研究了微粒的物理化学性质。通过 Andersen 级联撞击器研究了微粒的空气动力学行为。总体稳定性结果（对抗 RH 和温度）表明，含有 CIP 和 LEU 的微粒，以及与其他赋形剂组合的微粒，比单独含有 PVA 或 CD 的微粒更稳定。关于细颗粒分数和质量中值空气动力学直径（决定气溶胶化参数），发现储存后粒径和颗粒形状没有明显变化。在赋形剂中，LEU 具有许多优点，包括相对简单的配方、增强的空气动力学行为、方便的携带性和固有的稳定性提高。这种组合物可以作为治疗呼吸道感染和囊性纤维化的局部治疗的创新药物传递系统。
