Physiological Pharmaceutics

216 Physiological PharmaceuticsLocal pH has been demonstrated in vitro and ex-vivo studies to significantly affect therate and extent of absorption of ionizable compounds (Figure 9.8) 78 . Buffering a solutionto a target pH optimised for a particular drug should in theory, improve the absorptionacross the nasal epithelia. Reducing the pH of the mucosa enhanced the absorption ofvasopressin in rats 79 , but the rat tracheal cilia model shows that decreased pH has an adverseeffect on ciliary beat frequency 80 . Reduction in nasal pH has also been demonstrated toresult in lower blood glucose levels in dogs treated with intranasal insulin 81 .Recently, it has been demonstrated that buffers can be used to modify the pH of thehuman nasal cavity (Figure 9.9) 82 . Nasal anterior pH can be decreased when buffers of 0.1Mand above are used. Mildly acidic solutions produce an increase in pH, presumably due toreflux bicarbonate secretion. It is more difficult to modify the pH in the posterior of thenasal cavity and stronger buffers are required to do this.INTERSPECIES COMPARISONSThe majority of investigations published demonstrated the immense potential for nasal drugdelivery. However, the majority of studies have been carried out in animals. A comparisonof interspecies physiology and nasal clearance times is shown in Table 9.2. In humans, nasaldrug delivery is only useful for drugs which have a low molecular weight, are active in lowdoses and have good aqueous solubility. It should also be borne in mind that the level ofsedation used with different animals varies depending on ease of handling, and if generalanaesthetics are used, these will usually reduce mucociliary transport. As a result thecontribution of anaesthetics on published results can be difficult to assess.Table 9.2 Comparison of interspecies nasal cavity characteristics 83CONCLUSIONSNasal delivery is receiving a considerable amount of attention, but there is still a lack ofmuch fundamental physiological and biopharmaceutic information. For example, therelationship between pharmacokinetics and deposition patterns is largely unknown. Neitheris it a simple route for delivery since gastrointestinal involvement will also be a contributoryfactor in absorption.