Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):119-27. doi: 10.1089/jamp.2009.0757.
Pulmonary cell cultures are increasingly used to predict in vivo drug absorption after inhalation, similar to intestinal cell culture models that have already been well established to predict oral drug absorption. In contrast to the intestinal barrier, however, the so-called air-blood barrier of the lung is covered only with a thin film of liquid, on which the aerosol particles are deposited. The aim of this study was to investigate the relevance of this apical liquid film on the drug absorption rate when deposited as a dry powder formulation on pulmonary epithelial cells in vitro.
Budesonide and salbutamol sulfate were chosen as model drugs, and for each drug three generic aerosol powder formulations were used. Filter-grown monolayers of the human bronchial epithelial cell line Calu-3 were used as a model, using various volumes of apical liquid.
Although proven to be bioequivalent in vivo for each of the two drugs, the generic dry powder fomulations showed strikingly different epithelial transport rates in vitro, depending on the amount of apical liquid and the deposition technique, and suggesting that the dissolution of the aerosol particles in the apical liquid volume was rate limiting for the overall absorption rate. However, we found that the absorption rates of the formulations were similar after aerosolization and deposition in a multistage liquid impinger, which simulates more realistically the detachment of the drug crystals from the carrier lactose and their aerodynamic particle size-dependent deposition in the respiratory tract following inhalation from a dry powder inhaler. These data demonstrate the need for improved in vitro test systems to allow deposition of aerosol particles on the air-liquid interface cultivated cell monolayers by simultaneously taking into account aerodynamic properties.
肺细胞培养物越来越多地被用于预测吸入后的体内药物吸收，类似于已经建立良好的肠道细胞培养模型来预测口服药物吸收。然而，与肠道屏障不同，肺的所谓气-血屏障仅被一层薄的液体覆盖，气溶胶颗粒沉积在该液体上。本研究旨在探讨当以干粉制剂沉积在体外肺上皮细胞上时，沉积在该顶液膜上对药物吸收速率的相关性。
布地奈德和硫酸沙丁胺醇被选为模型药物，每种药物使用三种通用的气雾剂粉末制剂。使用各种顶液体积，将人支气管上皮细胞系 Calu-3 的滤过培养单层用作模型。
尽管两种药物的每个药物的体内生物等效性已得到证实，但通用干粉制剂在体外显示出截然不同的上皮转运率，这取决于顶液量和沉积技术，并表明气溶胶颗粒在顶液体积中的溶解是吸收总速率的限速步骤。然而，我们发现，在用多级液体冲击器进行雾化和沉积后，制剂的吸收速率相似，这更真实地模拟了从干粉吸入器吸入后，药物晶体从载体乳糖上脱离以及它们的空气动力学粒径依赖性在呼吸道中的沉积。这些数据表明需要改进体外测试系统，以便在同时考虑空气动力学特性的情况下，将气溶胶颗粒沉积在气液界面培养的细胞单层上。
