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.

To investigate drug conformity in various granule size-fractions and their effects on compressed tablets, granules with various physicochemical properties of active ingredients, manufactured by agitation and fluidized-bed methods, were assayed. It was observed that the drug contents of different size-fractions in various granules were affected by the surface polarity (P₀) of the component drug and excipients. Drugs possessing higher P₀ had lower drug content in the fine granule fraction, while drugs possessing lower P₀ had higher content. Regarding drug content in the large granule fraction, the relationship between P₀ was the opposite. The granules prepared by agitation exhibited various drug contents in different size-fractions, compared to the granules prepared by the fluidized-bed method. However, the drug uniformity of the resultant compressed tablets manufactured from these blended granules using a rotary tableting machine was showed almost suitable conforming and it was concluded that the drug homogeneity of compressed tablets was not strongly affected by the drug content uniformity of granule size-fractions.