The effect of molecular size on the nasal absorption of water-soluble compounds in the albino rat

Abstract

The nasal absorption of a range of water-soluble compounds with different molecular weights, 4-oxo-4H-1-benzopyran-2-carboxylic acid (mol. wt 190), p-aminohippuric acid (mol. wt 194), inulin (mol. wt 5200) and dextran (mol. wt 70 000), has been investigated in the male Wistar rat. Compounds were instilled into the nasal cavities of anaesthetized animals and, for comparison, similar doses were administered intravenously. Serial samples of bile and urine were collected for up to 6 h. Nasal absorption, estimated by comparison of the extent of excretion in bile and urine following intranasal and intravenous administration, was 100% for 4-oxo-4H-1-benzopyran-2-carboxylic acid (1 mg kg⁻¹), 75% for p-aminohippuric acid (1 mg kg⁻¹), 15% for inulin (0ṁ1 mg kg⁻¹) and 2ṁ8% for dextran (0ṁ25 mg kg⁻¹). The log molecular weight gave a good linear correlation with the log per cent intranasally absorbed (correlation coefficient of -0ṁ996). From the molecular weight relationship, these data infer aqueous channel mechanisms for the nasal absorption of water-soluble compounds.