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Optimizing ICS Suspensions for Nasal Use: The Influence of Solubility, Stability, Spray Volume, Dose, Log P and Receptor Binding

Hogger P.

Respiratory Drug Delivery 2014. Volume 1, 2014: 75-88.

Abstract:

Currently, the majority of nasally inhaled corticosteroids (ICS) are available as aqueous nasal suspensions. Although formulation as a suspension has some advantages, it also poses a number of challenges to ensure an efficacious and safe therapy for rhinitis. For local uptake into the nasal mucosa the ICS should possess sufficient solubility and permeability, both of which are governed by the compound’s log P. Besides the absolute solubility the rate of dissolution can also play a major role. The window for local absorption is very narrow due to rapid removal of undissolved drug particles by mucociliary clearance. While the suspension’s physical stability must be optimized to ensure reliable dosing, competing processes such as chemical and/or metabolic degradation may also affect the drug’s biopharmaceutical behavior. The anti-inflammatory effects of ICS depend on their dose and potency which is related to their receptor binding affinity. For nasal ICS, the spray volume may also be critical. In commercially available nasal sprays recommended doses for maintenance therapy are often delivered in fluid volumes per nostril that are known to be rapidly cleared by drain-off from the nasal cavity.