• Journal of Pharmaceutical Investigation
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• 제22권2호
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• pp.77-96
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• 1992

In recent years intranasal administration of drugs has received great attention as a convenient and efficent method of drug delivery because of its potential to improve the systemic effect of substances with a poor oral bioavailability. In addition to offering advantages such as rapid absorption, fast onset of action and avoiding the first -pass effect, it provides for delivery of drugs from very lipophilic drugs such as steroids to polar and hydrophilic drugs such as peptides and proteins. However, little is still known about the nature of various barriers existing in the nasal mucosae as well as mechanism by which these molecules are absorbed. This review article therefore intends to discuss nasal physiology, experimental methods and evaluation of absorption from the nasal cavity, factors influencing nasal absorption, mechanism of nasal absorption, approaches to improve the residence time and to obtain the sustained-release effect of intranasally administered drugs, promoters and mechanism for the enhancement of nasal absorption, Several examples for intranasal delivery of various systemically effective drugs will be reviewed and illustrated. Drug metabolism in the nasal mucosae and problems associated with intranasal administration of drugs will be also discussed.

• Journal of Pharmaceutical Investigation
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• 제23권2호
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• pp.71-80
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• 1993

The purpose of this study was to compare the intrinsic absorptivity of piperacillin in the jejunum and the nasal cavity, to investigate the effect of bile salts, fatty acids and their mixed micelles on the intestinal and nasal absorption of piperacilIin, to examine the reversibiIity of bile salt-fatty acid mixed micelles absorption promoting action and to design an effective intranasal drug delivery system for antibiotics. And absorption promoters used were bile salts [sodium cholate (NaC), sodium glycocholate (NaGC)], unsaturated fatty acids [oleic acid (OA), linoleic acid (LA)] and their mixed micelles (NaC-LA). The present study employed the in situ nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of piperacillin were $0.40{\pm}0.04{\times}10^{-5}cm/sec(mean{\pm}S.E)$ in the jejunum and $1.32{\pm}0.08{\times}10^{-5}\;cm/sec$ in the nasal cavity, which indicated that intrinsic absorptivity of piperacillin was greater in the nasal cavity than in the jejunum. When absorption promoters were used in the rat nasal cavity, the decreasing order of apparent piperacillin permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was NaC-LA $(4.62{\pm}0.16)$> NaC $(4.36{\pm}0.32)$>LA$(2.24{\pm}0.26)$ NaGC $(2.17{\pm}0.21)$>OA $(1.53{\pm}0.16)$. The increase in permeability of piperacillin was 3.5-fold in the rat nasal cavity and 1.5-fold in the rat jejunum for formulations containing NaC-LA mixed micelles as compared to those without absorption enhancer. The effect of NaC-LA mixed micellar solutions was synergistic and was greater than that with single adjuvant. The reversibility of nasal mucosal permeability was observed within approximately 2 hr after removal of NaCLA mixed micelles from the nasal cavity. These results suggest that NaC-LA mixed micelles can be used as nasal mucosal absorption promoters of poorly absorbed drugs.