Determination of baseline human nasal pH and the effect of intranasally administered buffers

The nose is becoming a common route of drug administration, however, little is known about the pH of the human nasal cavity. Local pH may have a direc t effect on the rate and extent of absorption of ionizable compounds and he nce this study was performed to investigate normal pH values and whether pH could be manipulated by various buffers. Twelve healthy volunteers partici pated in a study to measure pH in the anterior and posterior sites of the n asal cavity. Miniature pH electrodes were placed 3 cm apart in the nasal ca vity and a baseline was recorded for 30 min once the pH had stabilized. One hundred microlitres of isotonic solution was sprayed into the nostril and the pH was measured for 4 h post-dose. The following five formulations were tested: formulation A - sodium chloride (0.9%) at pH 7.2, formulation B so dium chloride (0.9%) at pH 5.8: Formulation C - Sorensens phosphate buffer (0.06 M) at pH 5.8: formulation D Sorensens phosphate buffer (0.13 M) at pH 5.8 and formulation E - formulation as (c) but adjusted to pH 5.0, Each fo rmulation also contained saccharin sodium (0.5%) as a taste marker for nasa l clearance, The time at which each subject detected the taste of saccharin was noted. The 30-minute baseline recording, prior to administration of th e nasal spray formulation demonstrates that there was both considerable int ersubject and intrasubject variation in nasal pH. The average pH in the ant erior of the nose was 6.40 (+ 0.11, - 0.15 S.D,) when calculated from H' va lues. The pH in the posterior of the nasal cavity was 6.27 (+ 0.13, -0.18 S .D.), The overall range in pH was 5.17-8.13 for anterior pH and 5.20-8.00 f or posterior pH. Formulation A caused the pH in the anterior part of the na sal cavity to reach a maximum of 7.06 in 11.25 min from the baseline of pH 6.14 (P < 0.05). The mean baseline pH was 6.5 for the posterior part of the nose which did not change over the recording period. Formulation B caused the anterior pH to increase from pl-l 6.60 to 7.25 within the first minute. This fell back to a mean pH of 7.07 over the first hour which was still si gnificantly above the baseline. It remained at this value for the remainder of the recording period. The initial average posterior pH was 6.32 and aga in this did not significantly change over the recording period. Formulation C produced a sustained increase in anterior nasal pH From a baseline pH of 6.57-7.12. A small transient decrease was observed in the pH in the poster ior of the nose but baseline pH of 6.6 was re-established within 15 min pos t dose. Formulation D significantly reduced anterior nasal pH From 6.30 to 5.87 by 30 min reaching a pH of 5.95 by 90 min where it remained for the re mainder of the recording period. The posterior baseline pH was 6.3 and intr oduction of the pH 5.8 buffer caused a slow increase over 90 min to pH 6.6. Formulation E increased anterior pH from 6.1 to 6.7 for the remainder of t he recording period. It had an insignificant effect on posterior nasal pH. The mean (+/- S.D.) time to taste saccharin for formulations A to E was 13. 42 +/- 10.21, 14.67 +/- 8.37, 11.67 +/- 8.08, 10.08 +/- 7.6 9.80 +/- 6.73 m in, respectively. There was no significant difference between the clearance times for the different formulations. In conclusion, average baseline huma n nasal pH is approximate to 6.3. Nasal anterior pH can be decreased when b uffers of 0.13 M and above are used. Mildly acidic solutions produce an inc rease in pH presumably due to reflux bicarbonate secretion. Posterior nasal pH was not altered by administration of any buffer except the 0.13 icl buf fer at pH 5.8. This produced a rise in posterior pH. (C) 2000 Elsevier Scie nce B.V. All rights reserved.