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Evaluation of the effect of polyethylene glycol 400 on the nasal absorption of nicardipine and verapamil in the rat.

This study has investigated the effect of polyethylene glycol (PEG) 400 on the intranasal absorption and ensuing pharmacokinetics of the calcium entry blockers nicardipine and verapamil in a rat model. To solutions of nicardipine in acetate buffer pH 5.0 and of verapamil in distilled water, PEG 400 was added in concentrations of 0-5%. The nasal bioavailability of nicardipine from plain buffered solution was 44%, and increased steadily to 56-79% in direct proportion to the amount of PEG 400 added. Verapamil, on the other hand, exhibited an intranasal bioavailability of 52% in the absence of PEG 400, and between 61-68% in the presence of increasing concentrations of PEG 400. None of the formulations tested was found to cause adverse effects on the morphology and integrity of the nasal mucosa.