Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
The University of Sydney, Sydney Nano Institute, Sydney, New South Wales 2006, Australia.
Anal Chem. 2020 Jun 16;92(12):8323-8332. doi: 10.1021/acs.analchem.0c00729. Epub 2020 May 22.
Solid state chemical analysis of pharmaceutical inhalation aerosols at the individual particle level has been an analytical challenge. These particles can range from a few nanometers to micrometers and are a complex mixture of drugs and excipients. Conventional analytical techniques cannot resolve the distribution of excipients and drugs at the submicrometer scale. Understanding the nanochemical composition of individual particles can be critical for pharmaceutical scientists to evaluate drug and excipient stability as well as the drug-drug or drug-excipient interactions that affect the aerosol performance of powders. Herein, we show the novel application of a combination of optical photothermal infrared (O-PTIR) spectroscopy and atomic force microscopy infrared (AFM-IR) spectroscopy to probe nanochemical domains of powders containing the inhaled corticosteroid fluticasone propionate and long-acting β2-agonist salmeterol xinafoate, which are widely used to treat asthma and chronic obstructive pulmonary disease. Three types of powder formulation were analyzed, including the commercial product Seretide, which is a physical mixture of the drugs with crystalline lactose, and two spray-dried powders containing the drugs along with either amorphous or crystalline lactose. We obtained spatially resolved O-PTIR and AFM-IR spectra confirming the presence of peaks related to fluticasone propionate at 1743, 1661, and 1700 cm, salmeterol xinafoate at 1580 cm, and lactose at 1030 and 1160 cm. The location of the drugs and lactose among the particles varied significantly, depending on the formulation type. For the first time, it was possible to map the drug distribution in individual aerosol particles. This is significant as such information has been lacking, and it will open an exciting research direction on how drug distribution affects the aerosol performance of powders and the consistency of dose uniformity. Further, these advanced spectroscopic techniques can be applied to study a wide range of pharmaceutical formulations.
对药物吸入气雾剂的固态化学分析在单个颗粒水平上一直是一个分析挑战。这些颗粒的直径范围可以从几纳米到几微米，并且是药物和赋形剂的复杂混合物。传统的分析技术无法在亚微米尺度上解析赋形剂和药物的分布。了解单个颗粒的纳米化学组成对于药物科学家评估药物和赋形剂的稳定性以及影响粉末气溶胶性能的药物-药物或药物-赋形剂相互作用至关重要。在这里，我们展示了光学光热红外（O-PTIR）光谱和原子力显微镜红外（AFM-IR）光谱相结合的新应用，以探测含有吸入性皮质类固醇丙酸氟替卡松和长效β2-激动剂沙美特罗昔萘酸酯的粉末的纳米化学领域，这些药物广泛用于治疗哮喘和慢性阻塞性肺疾病。分析了三种类型的粉末配方，包括商业产品 Seretide，它是药物与结晶乳糖的物理混合物，以及两种含有药物的喷雾干燥粉末，其中含有无定形或结晶乳糖。我们获得了空间分辨的 O-PTIR 和 AFM-IR 光谱，证实了在 1743、1661 和 1700 cm 处存在与丙酸氟替卡松相关的峰，在 1580 cm 处存在沙美特罗昔萘酸酯，在 1030 和 1160 cm 处存在乳糖。药物和乳糖在颗粒中的位置因配方类型而异。这是首次有可能在单个气溶胶颗粒中绘制药物分布。这一点非常重要，因为缺乏此类信息，它将开辟一个令人兴奋的研究方向，即药物分布如何影响粉末的气溶胶性能和剂量均匀性的一致性。此外，这些先进的光谱技术可用于研究广泛的药物配方。
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