Motzwickler-Németh Anett, Party Petra, Simon Péter, Sorrenti Milena, Ambrus Rita, Csóka Ildikó
Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6720 Szeged, Hungary.
Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Hungary.
Pharmaceutics. 2024 Oct 24;16(11):1361. doi: 10.3390/pharmaceutics16111361.
BACKGROUND/OBJECTIVES: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery-expressly in the lung-seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF).
Using the LeanQbD software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR).
Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility.
This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems.
背景/目的：基于环糊精的金属有机框架（CD-MOFs）的研究仍处于起步阶段，但其在药物递送方面的潜力——尤其是在肺部给药——似乎很有前景。我们旨在利用冷冻干燥法开创一种制备CD-MOFs的新方法。由γ-环糊精（γCD）和钾阳离子（K）组成的金属有机框架被用于包裹水溶性差的模型药物布洛芬（IBU），以治疗囊性纤维化（CF）。
使用LeanQbD软件（v2022），我们基于质量源于设计（QbD）理念设计实验。根据QbD，我们确定了三个最关键的因素，即IBU与γCD的摩尔比、孵育时间和有机溶剂的百分比。利用光学显微镜、扫描电子显微镜（SEM）和激光衍射观察样品的形态和粒径。此外，通过差示扫描量热法（DSC）、X射线粉末衍射（XRPD）、傅里叶变换红外光谱（FT-IR）和核磁共振光谱（NMR）对产物进行表征。
基于表征，我们得出结论，使用冷冻干燥法也能形成γCD-MOF/IBU复合物。使用具有最佳空气动力学性能的制剂，根据安德森级联撞击器测量，我们分别实现了38.10±5.06和47.18±4.18的细颗粒分数百分比（FPF%）。通过这些制剂，我们实现了快速溶解曲线并提高了IBU的溶解度。
本研究成功证明了冷冻干燥法在生产用于吸入性IBU递送的γCD-MOFs方面的创新应用。该方法能够改变粒径，这对成功的肺部摄取至关重要，强调了将这些制剂作为有效递送系统进行进一步研究的必要性。
