| Summary: | This thesis investigates whether the formation of ion-pairs can influence the delivery of salbutamol to the airways of the lung. Presenting a drug with an excess of oppositely charged ion can force it to form an ion-pair complex, and this complex can modify a drug’s dissolution or transport across epithelia without chemically altering the drug. The binding of salbutamol with pharmaceutically relevant counter ions was studied. It was found that the larger more hydrophobic counter ions bound more tightly to the drug. Only 2 of the investigated counter ions had a significant effect on the LogD7.4 of salbutamol. Phytic acid was investigated as a novel counter ion. Generation of phytic acid derivatives was attempted via chemical synthesis however this method did not yield a pure sample. The binding of phytic acid was studied and was found to be stronger than the other investigated counter ions, although no change in the logD7.4 of salbutamol was observed. Salbutamol ion-pair dry powders with particle size < 5 μm were generated via spray drying. Impactor testing found that the powders were in the respirable range. Stability testing after 4 weeks found that the powders containing both PVP and l-leucine were the most stable after this time. The biocompatibility of the counter ions with Calu-3 human bronchial epithelial cells was assessed and all counter ions were shown to be well tolerated. The effect of the ion-pairs on the transport of salbutamol across a monolayer of Calu-3 cells found a significant difference in the transport of the sulfate, gluconate and phytate ion-pairs when compared with salbutamol base. There was no significant difference in the dissolution of the phytate or octanoate powders when compared with the base. An in vivo bronchoprotection study of salbutamol base and phytate was performed. The work in this thesis suggests that an ion-pairing strategy is suitable for use to prolong drug action in the lung.
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