Bulk to Nanometer-Scale Infrared Spectroscopy of Pharmaceutical Dry Powder Aerosols

Abstract

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 −1 , salmeterol xinafoate at 1580 cm −1 , and lactose at 1030 and 1160 cm −1 . 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.

Resolving Nanocomposite Interfaces via Simultaneous Submicrometer Optical‐Photothermal Infrared‐Raman Microspectroscopy

“…Characteristic IR absorbance peaks ( Figure 1d) at 1738 cm −1 (CO stretching), [21] 1470 cm −1 (-CH 2 -scissoring), [22] and 1173 cm −1 (C-O-C valence vibrations, C-O stretching) [2] along with corresponding active Raman bands ( Figure 1e) at 2876 cm −1 (-CH 2 -/-CH 3 stretching) [2] and 970 cm −1 (Si-O stretching) [23] taken at targetspecific locations near peripheral and central regions confirm the presence of PODA and the underlying native oxide layerpassivated Si-wafer substrate, which agrees well (98.1%) with Wiley's KnowItAll IR spectral database ( Figure S2, Supporting Information) and conventional Raman spectra ( Figure S3, Supporting Information) independently collected. O-PTIR+R has very recently been used to characterize depth-resolved molecules in living cells, [7] polymorphic amyloid aggregates in neurons, [24] sub-micrometer atmospheric particulates, [25] pharmaceutical dry-powder aerosols, [26] <10-µm organic contaminants on hard drives, [27] bioplastic composite interfaces, [28] high-explosive trace materials, [29] and Ruddlesden-Popper hybrid perovskite crystals exhibiting peripheral 2D/3D heterostructure formation, [30] which show excellent correlation to conventional FTIR absorbance spectra.…”

Background noise suppressed high-throughput mid-infrared photothermal microscopy via pupil engineering

“…[10][11][12] After the initial inception in 2016, 10 MIP has been progressively evolving from the proof of concepts to commercialization and wide applications. [13][14][15][16] Technically, Delong Zhang et al…”

Bond-selective interferometric scattering microscopy

“…This emerging technique has been recognized widely in the chemical imaging field and continuously evolved in various geometries including scanningbased [30,35,36,37,38] and wide-field [39,40,41,42,43,44] illumination. A wide range of applications spanning from material science to life science has been reported by scanning MIP techniques [45,46,47,48,49,50,51,52].…”