Role of Low-Substituted Hydroxypropylcellulose in Dissolution and Bioavailability of Novel Fine Granule System for Masking Bitter Taste

Abstract

Coated fine granules with water-insoluble film composed primarily of ethylcellulose, containing 20% of sparfioxacin (SPFX) and various amounts of low-substituted hydroxypropylcellulose (L-HPC) (0—52%) in the cores and which masked the bitter taste of SPFX, were orally administered to fasting rats to determine the effect of L-HPC on bioavailability. The release of SPFX in water from four kinds of these coated fine granules containing 0, 25, 40 and 52% of L-HPC showed the pseudo first order kinetics, followed by the second phase, with refractive points between 0.25 and 0.5h. The rate constant (K1) up to 0.25h increased with an increase in of the amount of L-HPC in the core, and the rate constant (K2) in subsequent release (the second phase) was lower than K1in each fine granule. Areas under plasma concentration-time curves (AUC) of SPFX and the peak plasma SPFX levels (Cmax) after oral administration of coated fine granules lacking L-HPC to fasting rats were suppressed to one-eighth and one-ninth, respectively, of those obtained from the core granules that rapidly released SPFX. However, AUC and Cmax from the coated fine granules increased linearly with an increase in the amount of L-HPC in the cores, and nearly equaled those from the core fine granules when the content of L-HPC was 52%. These results confirmed that the addition of L-HPC to the cores increases not only the dissolution rate but also the bioavailability of SPFX. © 1994, The Pharmaceutical Society of Japan. All rights reserved.