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Purpose: To measure the penetration of fluorescein into the anterior ocular compartments after exposure of the cornea to a mist of aerosol droplets.Methods: This was an open-label proof-of-principle trial. Eighteen healthy volunteers were asked to participate. A conventional (50 μL) drop of fluorescein solution (20 mg/mL) was administered to the right eye; an ocular mist (10 μL) of the same solution was applied to the left eye. Autofluorescence (photons/s) was measured in the cornea, the anterior chamber (AC), and the lens before administration and at 1, 2, 5, 10, 20, 50, and 100 min thereafter. The area under the curve (AUC) was calculated. For the vitreous cavity, measurements were performed at baseline and after 100 min.Results: All participants completed the study. AUC (mean±SD) for the cornea was (363±431)×10(4) photons after drop application and (154±265)×10(4) photons after the mist (P=0.005). For the AC, these values were (6.9±10.3)×10(4) and (2.9±5.4)×10(4) photons, respectively (P=0.14). Autofluorescence data obtained in the lens did not allow reliable AUC calculations. Autofluorescence in the vitreous at 100 min did not significantly exceed the level at baseline.Conclusion: It was demonstrated that fluorescein applied to the ocular surface with the spray device enters the AC. The total amount of fluorescein molecules reaching the ocular surface by the 2 methods of administration, however, is not equivalent. Therefore, no definitive conclusions on relative bioavailability can be drawn from this experiment. [ABSTRACT FROM AUTHOR]

Nasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g. vaccines, biologics and drugs with action in the brain or sinuses, to local and systemic therapeutic targets. Innovations and new tools/knowledge are required to design products to deliver these therapeutic agents to the right target at the right time in the right patients. We report the outcomes of an expert meeting convened to consider gaps in knowledge and unmet research needs in terms of (i) formulation and devices, (ii) meaningful product characterization and modeling, (iii) opportunities to modify absorption and clearance. Important research questions were identified in the areas of device and formulation innovation, critical quality attributes for different nasal products, development of nasal casts for drug deposition studies, improved experimental models, the use of simulations and nasal delivery in special populations. We offer these questions as a stimulus to research and suggest that they might be addressed most effectively by collaborative research endeavors.

Background: Monodisperse salbutamol inhalers were compared to select the optimal mass median aerodynamic diameter: 4.0, 5.0 or 6.0 microm., Methods: Fifteen mild asthmatic patients participated. In all a FEV(1)-response of >12% (vs. baseline) or >200 mL after inhalation of 200 microg salbutamol was measured. Each patient was studied four times with intervals of 1 week (three active and one placebo inhaler). First, 10 microg salbutamol was administered, followed by 10, 20, and 40 microg, resulting in cumulative doses of 10, 20, 40, and 80 microg salbutamol. The FEV(1) and other lung function parameters were assessed at baseline and 30 min after inhalation of each consecutive dose. Five minutes later a next inhalation was given., Results: The 4.0- and 5.0-microm droplets did not differ from placebo (p = 0.502, p = 0.127), but the 6.0-microm droplets differed significantly (p = 0.003). The difference between 6.0-4.0 microm droplets was significant (p = 0.020), but not between the 6.0-5.0 microm droplets (p = 0.129). The FEV(1) increase after 80-microg salbutamol for the 6.0-microm droplets was 243 +/- 144 mL., Conclusions: The study showed that the 6.0-microm droplets differed from the others in terms of FEV(1)-improvement, and hence, are the most efficacious of the three evaluated.