Ion-pairs – a novel formulation strategy to alter drug disposition in the lungs

Bridie Dutton, Robyn Sadler, Ben Forbes, Stuart Jones

The lungs are an attractive route for the administration of both systemically and locally acting medicines for numerous reasons, including their large surface area and relative lack of metabolic activity for many drug molecules. Inhaled medicine administration does, however, also have its challenges. A major issue for pulmonary drug delivery is the rapid elimination of the active compound for the lungs, meaning that many medicines must be administered multiple times a day, leading to poor patient compliance. An interesting strategy for altering the post-deposition fate of drug delivered to the lungs by inhalation is the use of ion-pairs. The formation of drug ion-pairs offers an opportunity to alter the biopharmaceutical properties of inhaled compounds without altering their structure or pharmacological activity. In order for a drug to form an ion-pair an excess of counter ion must be used. Existing medicines that contain counter ions, such as salbutamol sulfate, do not take advantage of their ion-pairing potential. In this study the ion-pairing between salbutamol and 3 counter ions (sulfate, gluconate and octanoate) was investigated using Fourier Transformed infra-red spectroscopy, and it was found that the salbutamol gluconate complex is stronger than that of salbutamol sulfate with binding constants of 2.270 and 1.569, respectively. Salbutamol octanoate binding could not be quantified due to the complex nature of the ion-pair formed. The results of this study illustrate how ion-pairs can be formed and characterised in preparation for future pharmacokinetic assessment in the lungs.

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