Respiratory Technology, The Woolcock Institute of Medical Research, The University of Sydney, Australia; Discipline of Pharmacology, Faculty Medicine, The University of Sydney, Australia.
Graduate School of Pharmacy Health-Pharmacy, University of Technology Sydney, Sydney, Australia.
Eur J Pharm Biopharm. 2014 Jan;86(1):38-45. doi: 10.1016/j.ejpb.2013.02.020. Epub 2013 Mar 22.
Two solution-based pressurised metered dose inhaler (pMDI) formulations were prepared such that they delivered aerosols with identical mass median aerodynamic diameters, but contained either beclomethasone dipropionate (BDP) alone (glycerol-free formulation) or BDP and glycerol in a 1:1 mass ratio (glycerol-containing formulation). The two formulations were deposited onto Calu-3 respiratory epithelial cell layers cultured at an air interface. Equivalent drug mass (∼1000ng or ∼2000ng of the formulation) or equivalent particle number (1000ng of BDP in the glycerol-containing versus 2000ng of BDP in the glycerol-free formulation) were deposited as aerosolised particles on the air interfaced surface of the cell layers. The transfer rate of BDP across the cell layer after deposition of the glycerol-free particles was proportional to the mass deposited. In comparison, the transfer of BDP from the glycerol-containing formulation was independent of the mass deposited, suggesting that the release of BDP is modified in the presence of glycerol. The rate of BDP transfer (and the extent of metabolism) over 2h was faster when delivered in glycerol-free particles, 465.01ng±95.12ng of the total drug (20.99±4.29%; BDP plus active metabolite) transported across the cell layer, compared to 116.17ng±3.07ng (6.07±0.16%) when the equivalent mass of BDP was deposited in glycerol-containing particles. These observations suggest that the presence of glycerol in the maturated aerosol particles may influence the disposition of BDP in the lungs.
两种基于溶液的压力定量吸入器（pMDI）制剂被制备成能够输送具有相同质量中值空气动力学直径的气雾剂，但含有单独的丙酸倍氯米松（BDP）（无甘油配方）或 BDP 和甘油以 1:1 的质量比（含甘油配方）。这两种制剂被沉积在培养在气-液界面的 Calu-3 呼吸道上皮细胞层上。沉积在气-液界面上的细胞层上的等效药物质量（约 1000ng 或两种制剂中约 2000ng 的 BDP）或等效颗粒数（含甘油制剂中 1000ng 的 BDP 与无甘油制剂中 2000ng 的 BDP）被沉积为雾化颗粒。沉积无甘油颗粒后 BDP 穿过细胞层的转移率与沉积的质量成正比。相比之下，含甘油制剂中 BDP 的释放与沉积的质量无关，表明在甘油存在的情况下 BDP 的释放被修饰。在无甘油颗粒中输送时，BDP 的转移率（和代谢程度）在 2 小时内更快，有 465.01ng±95.12ng 的总药物（20.99±4.29%；BDP 加活性代谢物）穿过细胞层，而当沉积等效质量的 BDP 时，只有 116.17ng±3.07ng（6.07±0.16%）穿过细胞层。这些观察结果表明，成熟的气雾剂颗粒中甘油的存在可能会影响 BDP 在肺部的处置。
