Cheng Y S, Yazzie D, Gao J, Muggli D, Etter J, Rosenthal G J
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
J Aerosol Med. 2003 Spring;16(1):65-73. doi: 10.1089/089426803764928374.
Polylactic acid (PLA) powders have been used as vector particles to carry pharmaceutical material. Drugs incorporated in the PLA powder can be retained in the lung for a longer period and may be more effective than free-form drugs. A new formulation of L-PLA dry powder, which was easy to disperse in the air, was produced by using a supercritical technology. The L-PLA powder was characterized in terms of physical particle size and aerodynamic size as generated with a Turbuhaler dry powder inhaler (DPI). Electron microscopy analysis of the particles indicated that they were individual particles in bulk form and became aggregate particles after generation by the Turbuhaler. Aerodynamic particle size analysis using both an Aerodynamic Particle Sizer (APS) aerosol spectrometer and Andersen impactor showed that the aerodynamic size decreased as the flow rate in the Turbuhaler increased from 28.3 to 90 L min(-1). Deposition patterns in the human respiratory tract were estimated using a realistic physical replica of human airways. Deposition of the L-PLA was high (80.8%) in the oral airway at 28.3 L min(-1) and an average of 73.4% at flow rates of 60 and 90 L min(-1). In the lung region, the deposition totaled 7.2% at 28.3 L min(-1), 18.3% at 60 L min(-1), and 17.6% at 90 L min(-1). These deposition patterns were consistent with aerodynamic size measurement, which showed 76 to 86% deposition in the USP/EP (US Pharmacopoeia/European Pharmacopoeia) induction port. As the flow rate increased, fewer aggregates were formed resulting in the smaller aerodynamic particles. As a result, more particles penetrated the oral airways and were available for deposition in the lung. Our results showed that L-PLA particles as manufactured by the supercritical technology could be used in a DPI that does not require the use of carrier particles to facilitate aerosol delivery.
聚乳酸（PLA）粉末已被用作载体颗粒来运载药物材料。掺入PLA粉末中的药物可以在肺部保留更长时间，并且可能比游离形式的药物更有效。通过使用超临界技术制备了一种易于在空气中分散的新型L-PLA干粉制剂。用Turbuhaler干粉吸入器（DPI）对L-PLA粉末的物理粒径和空气动力学粒径进行了表征。颗粒的电子显微镜分析表明，它们是散装形式的单个颗粒，经Turbuhaler产生后变成聚集颗粒。使用空气动力学粒径分析仪（APS）气溶胶光谱仪和安德森撞击器进行的空气动力学粒径分析表明，随着Turbuhaler中的流速从28.3增加到90 L min⁻¹，空气动力学粒径减小。使用逼真的人体气道物理模型估计了L-PLA在人体呼吸道中的沉积模式。在流速为28.3 L min⁻¹时，L-PLA在口腔气道中的沉积率很高（80.8%），在流速为60和90 L min⁻¹时平均沉积率为73.4%。在肺部区域，在流速为28.3 L min⁻¹时沉积总量为7.2%，在流速为60 L min⁻¹时为18.3%，在流速为90 L min⁻¹时为17.6%。这些沉积模式与空气动力学粒径测量结果一致，该测量结果显示在美国药典/欧洲药典诱导端口中的沉积率为76%至86%。随着流速增加，形成的聚集体减少，导致空气动力学颗粒变小。结果，更多颗粒穿透口腔气道并可用于在肺部沉积。我们的结果表明，通过超临界技术制造的L-PLA颗粒可用于不需要使用载体颗粒来促进气溶胶递送的DPI中。
