Ciclesonide and budesonide suspensions for nebulization delivery: An in vivo inhalation biopharmaceutics investigation

In this study, the main objective was to investigate the in vivo inhalation biopharmaceutics in the aspects of dissolution, mucociliary clearance, absorption and tissue binding using intratracheally administered budesonide and ciclesonide suspensions as model drugs. In doing so, this study first developed a method to differentiate between dissolved and undissolved ciclesonide in the lungs for evaluating in vivo dissolution. Following deposited in rat airways, the drug particles underwent rapid dissolution and mucociliary clearance, leading to the complete removal of drugs from the airways within 2 h and a limited absorption time less than 2 h. Upon dissolution, budesonide and ciclesonide were taken up and retained in the lung tissues for up to 12 h and 24 h, respectively. The in vivo dissolution profiles in the airways exhibited the sameness as the in vitro counterparts in a 0.5% sodium dodecyl sulfate solution as indicated by the similarity factor f2. The efficacy results in a lipopolysaccharide induced lung injury model showed that the duration of local anti-inflammatory was dependent on the drug levels in the lung tissues, but not on the in vitro/in vivo dissolution and plasma pharmacokinetics. The present results demonstrated that ciclesonide suspension has the potential to achieve once-daily dosing for nebulization therapy and the in vitro dissolution profile has limited usefulness in predicting in vitro–in vivo correlation.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research