Abstract
Aerosol dynamics is important to quantify in drug delivery to the lungs with the aim of delivering therapeutics to a target location and optimising drug efficacy. The macrocycle (2-hydroxypropyl)-β-cyclodextrin (2-HP-β-CD) is thought to alleviate symptoms associated with neurodegenerative diseases when inhaled but the hygroscopic response is not well understood. Here we measure the hygroscopic growth of individual aqueous aerosol containing 2-HP-β-CD in optical tweezers through analysis of morphology-dependent resonances arising in Raman spectra. Droplets are analysed in the size range of 3-5 μm in radius. The evolving radius and refractive index of each droplet are measured in response to change in relative humidity from 98-20% to determine mass and radius based hygroscopic growth factors, and compared with dynamic vapour sorption measurements. Bulk solution refractive index and density measurements were used in accordance with the self-consistent Lorenz-Lorentz rule to determine melt solute and droplet properties. The refractive index of 2-HP-β-CD was determined to be 1.520 ± 0.002 with a density of 1.389 ± 0.005 g cm-3. To our knowledge, we show the first aerosol measurements of 2-HP-β-CD and determine hygroscopicity. By quantifying the hygroscopic growth and physicochemical properties of 2-HP-β-CD, the impact of aerosol dynamics can be accounted for in tailoring drug formulations and informing models used to predict drug deposition patterns within the respiratory system.
Highlights
Determining and controlling aerosol properties is important for targeted and effective drug deposition patterns where the environment of the drug path towards and into the respiratory tract or through the olfactory system is known to influence pharmaceuticals.[1]
Recent studies have shown characterisation of the physiochemical properties of aerosolised medicinal agents used in drug delivery to the lung, e.g. salbutamol sulphate,[3] where the aging of the droplet as it responds to rapid changes in relative humidity (RH) and temperature during inhalation is known to significantly impact aerosol properties
We measure the hygroscopic growth of (2-hydroxypropyl)-b-cyclodextrin (2-HP-b-CD) which, as a medicinal agent, is thought to alleviate symptoms associated with neurodegenerative diseases for use in drug inhalation formulations.[1,15,16]
Summary
Determining and controlling aerosol properties is important for targeted and effective drug deposition patterns where the environment of the drug path towards and into the respiratory tract or through the olfactory system is known to influence pharmaceuticals.[1]. We measure the hygroscopic growth of (2-hydroxypropyl)-b-cyclodextrin (2-HP-b-CD) which, as a medicinal agent, is thought to alleviate symptoms associated with neurodegenerative diseases for use in drug inhalation formulations.[1,15,16] The hygroscopicity of microscopic sized aerosol droplets is determined on a single droplet basis using Raman tweezers[17,18] and compared with dynamic vapour sorption (DVS) humidity isotherm measurements.[19,20]. The RI of solute was retrieved using the self-consistent Lorenz– Lorentz medium approximation, derived from the Clausius– Mossotti relation.[34]
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