Department of Pharmaceutics, School of Pharmacy, King Khalid University, Guraiger, Abha, Kingdom of Saudi Arabia.
School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
PLoS One. 2021 Apr 13;16(4):e0249683. doi: 10.1371/journal.pone.0249683. eCollection 2021.
This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.
本研究旨在开发和表征葛根素干粉吸入剂（DPI）制剂用于肺部给药。通过微粉化实现可吸入颗粒大小（<2μm），并通过扫描电子显微镜（SEM）检查其形态。通过傅里叶变换红外光谱（FTIR）、拉曼共聚焦显微镜、X 射线粉末衍射（XRD）和差示扫描量热法（DSC）方法分析粉末混合物中葛根素-赋形剂的相互作用。使用双级撞击器（TSI），在 60 L/min 的流速下对粉末制剂进行体外雾化，并采用经过验证的 HPLC 方法定量药物。在粉末制剂中未观察到药物与赋形剂之间存在显着相互作用。药物的细颗粒分数（FPF）单独为 4.2%，而含有雾化增强剂的制剂则增加了五到六倍。含有乳糖作为大载体的制剂产生 32.7%的 FPF，当添加分散增强剂亮氨酸和硬脂酸镁时，进一步增加（分别为 40.8%和 41.2%）。拉曼和 FTIR 技术是理解粉末制剂中葛根素结构完整性和稳定性的非常有用的工具。葛根素与所用赋形剂相容，所开发的 DPI 制剂可被认为是用于以非常低剂量治疗各种疾病的肺部给药的有效制剂。
