Intranasal administration

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I was wondering whether any one might be able to point me in the right direction of acceptable pH's for intranasal substance administration in hamsters - is pH 4.0 acceptable?

It will depend on the strength of the solution (1M compared to 1mMolar).

Why does it need to be pH 4, as within a few seconds the natural secretions and reactions will raise it to more neutral pH?  The vehicle will also be important as to whether it is buffered or not (I assume it will be in acetate/acetic acid buffer at the pH?) or whether it is some other form of vehicle (liposomes or emulsion).

This paper produced by the Joint Working Group on Refinement may help:

Morton, D.B., Jennings, M., Buckwell, A. Ewbank, R, Godfrey, C, Holgate B., Inglis I, James R, Page, C, Sharman, I, Verschoyle, R, Westall L and A.B. Wilson (2001) Refining procedures for the administration of substances. Third Report of the BVA-AWF/FRAME/RSPCA /UFAW Joint Working Group on Refinement.  Laboratory Animals 35: 1 – 41.

I guess that the volume of solution will be of consideration; a larger volume may present challenges in being neutralised by existing nasal secretions and there may be potential for iatrogenic damage to nasal mucosa. This could be a consideration from a pathological evaluation perspective. Is it possible to include control animals with carrier solution without the test item, which is at the same pH?

Bottom line: pH should be 4.5-6.5 to avoid damaging nasal mucosa, but the pKa of the drug molecule is important.