Role of low-substituted hydroxypropylcellulose in dissolution and bioavailability of novel fine granule system for masking bitter taste.
Coated fine granules with water-insoluble film composed primarily of ethylcellulose, containing 20% of sparfloxacin (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 0.5 h. The rate constant (K1) up to 0.25 h increased with an increase [corrected] of the amount of L-HPC in the core, and the rate constant (K2) in subsequent release (the second phase) was lower than K1 in 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.
Shirai
Y
Y
Pharmaceutical Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Sogo
K
K
Fujioka
H
H
Nakamura
Y
Y
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005079:Excipients; D024841:Fluoroquinolones; D007275:Injections, Intravenous; D008297:Male; D011208:Powders; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013649:Taste / Q000187:drug effects*
D000890:Anti-Infective Agents; D005079:Excipients; D024841:Fluoroquinolones; D011208:Powders; D015363:Quinolones; D002482:Cellulose; C008079:hydroxypropylcellulose; C061363:sparfloxacin