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Drug Delivery to the Nasal and Paranasal Cavities - Critical Cast Dimensions and Aerosol Dynamics

Schuschnig U, Keller M, Klopfer E, Kruner A, Luber M, Zimmermann J, Knoch M.

Respiratory Drug Delivery 2008. Volume 1, 2008: 227-238.

Abstract:

The idea of aerosol transport into the sinuses, which are virtually non-vented cavities, via the so called “vibrating” or “sonic aerosols” suggests that pressure fluctuations increase aerosol diffusion and ventilate dead spaces by flow induction. However, the physical boundary conditions like pulsation frequency, aerosol size and flow rate have to be considered for an efficient transport as well as sinus anatomy. The influence of the above-named factors on drug delivery to the nasal and paranasal cavities was studied in two human nasal cast models (NC) with different nasal cavity volumes of about 17 and 60 mL, each. One mL of a Levofloxacin solution (100 mg/mL) was aerosolized into the NCs by a VibrENT prototype nebulizer generating a slow, high density aerosol (MMD = 3.7μm) via a perforated vibrating membrane in connection with an adjustable pulsation source. Total paranasal cavity deposition was highest in both NCs (~20 % of label claim) configured with ostia of 1 and 3 mm in diameter and sinus volumes of 7, 12 and 23 mL when VibrENT was operated at flow rates below 3 L/min and a pulsation frequency of 36 Hz. Delivery efficiency decreased at higher frequencies, higher flow rates and with larger aerosol droplets. Omission of pulsation resulted in no paranasal deposition and a drop in nasal cavity deposition from more than 50% to about 6%. Drug deposition to the sinuses is also significantly (p<0.01) affected by the ostium diameter and sinus volume, being lowest (~0.2 %) at a large ostium diameter (6 mm) and a low sinus volume (7 mL). Administration of pulsating, low velocity dense aerosols making use of flow rates < 3 L/min seemingly led to high aerosol residence times in the nose and was associated with substantial drug deposition in nasal and paranasal cavities. Clinical studies are warranted to support our in vitro study results.