Abstract
Problem
Drug delivery to the sinuses via aerosols appears to be a very difficult task, since the paranasal cavities are virtually non-vented cavities. However, there is a scientifically traceable approach to transport aerosol to the sinuses via pressure differences using so-called “vibrating” or “sonic” aerosols which suggests that pressure fluctuations increase aerosol diffusion and ventilate dead spaces by flow induction.
Methods
The influence of droplet size, vibration frequency and flow rate on drug delivery to the nasal and paranasal cavities was studied in a human nasal cast model (NC). One ml of a Levofloxacin solution (100 mg/ml) was aerosolized into the NC 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.
Results
Total paranasal cavity deposition was highest (-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 1/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).
Conclusion
It is possible to deliver aerosol to the sinuses but physical boundary conditions like pulsation frequency, aerosol size and flow rate have to be considered for an efficient transport as well as sinus anatomy. PARI VibrENT addresses these requirements.
Significance
Efficient drug transport to the sinuses enables novel therapeutic approaches.
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