Relationship between Calcein Disposition in Nasal Cavity and Blood Concentration after Intranasal Administration of Viscous Calcein-Loaded Starch Solution in Rats

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  • カルセイン含有デンプン溶液の経鼻投与後の鼻腔滞留性とカルセイン血中動態との関係

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Abstract

<p>The present work was to estimate pharmacokinetically calcein absorption and mucoadhesion after intranasal administration of calcein-loaded starch viscous solution in rats. Two experimentations (close and open systems) were employed based on the method of Hirai et al. In the closed system, viscous starch solution remained in the nasal cavity after administration, because the rat pharynx was occluded by a silicone gum in the horizontal setting. In the open system, the rat was fixed at an angle of 60° relative to the horizontal plate and viscous starch solution was able to flow away to the pharynx. With the increasing concentration of starch, the blood concentration and bioavailability of calcein obtained in the open system were made nearly equal to those obtained in the closed system. This trend was found to be associated with the apparent viscosity of the starch solution. These results suggested that a viscous starch solution (gel system) with higher viscosity adequately adhered to the nasal mucosa, resulting in resistance to the physical clearance by an inclination. However, in the closed system, blood concentration and bioavailability decreased with an increasing concentration of starch. This was most likely due to a reduction in the contact surface area of the viscous starch solution to the nasal mucosa and partially to a decrease in the release rate of calcein. For poorly absorbable drugs and drugs which need “rapid onset” of pharmacological action, a microparticulate system could be more promising than a gel system (viscous solution) to improve contact surface area and drug release.</p>

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