Enhancement of dissolution and bioavailability of flurbiprofen by low molecular weight chitosans.
The dissolution behavior and absorption of flurbiprofen (FP) following oral administration from:three types of chitosans (LM chitosans), with different molecular weights and degree of acetylation, have been studied in comparison with those of the drug alone. The solubility of FP increased with concentrations of LM chitosan, especially in the case of C-III, with the highest degree of deacetylation degree among the three chitosans. This indicates that amino groups of LM chitosan play an important role in its interaction with FP. Moreover, spectroscopic studies, including NMR data, indicate that the binding involves interactions between the carboxyl group of FP and the amino group of the chitosans. The dissolution rates of FP for a C-III kneaded mixture were enhanced with increasing amounts of C-III. The oral absorption of FP from a C-III kneaded mixture was improved to a significant extent, compared to FP alone. These results suggest that FP from LM chitosan kneaded mixture increases the dissolution rate and improves the bioavailability of the drug by the formation of a water-soluble complex.
Anraku
M
M
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Arahira
M
M
Mady
F M
FM
Khaled
K A
KA
Yamasaki
K
K
Seo
H
H
Imai
T
T
Otagiri
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008970:Molecular Weight; D019999:Pharmaceutical Solutions; D051381:Rats; D012995:Solubility; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D019999:Pharmaceutical Solutions; D005480:Flurbiprofen; D048271:Chitosan