Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles.
In the therapy of rheumatoid arthritis, ibuprofen (IBU) is widely used; however, it has been limited the clinical use by its systemic side effect, such as gastrointestinal lesions. Therefore, we prepared topical gel ointment used IBU solid nanoparticles (IBUnano-gel formulation). In addition, we demonstrated their anti-inflammatory effect by using arthritis model rat (adjuvant-induced arthritis rat, AA rat). The gel formulations were prepared using additives (Carbopol 934, 2-hydroxypropyl-β-cyclodextrin and methylcellulose) and bead mill-method. The IBU particle size in the IBUnano-gel formulation was 208 nm. The increase in inflammation of the hind feet of AA rats was attenuated by the treatment with the IBUnano-gel formulation, and preventive effect was higher than that of a gel formulation containing IBUmicroparticles (IBUmicro-gel formulation, mean particle size 85.4 μm); the accumulation and permeability through the skin of IBU from the IBUnano-gel formulation were significantly larger in comparison with the IBUmicro-gel formulation. Further, no gastrointestinal lesions were observed in AA rats following the repetitive administration of the 5% IBUnano-gel formulation (0.30 g) for 42 days (once a day). These results suggest that the dermal application of IBU-nanoparticles provide effective and efficient therapy that spares patients from unwanted side effects.
Faculty of Pharmacy, Kindai University.
Noriaki
N
Nagai
Tadatoshi
T
Tanino
Yoshimasa
Y
Ito
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004195:Disease Models, Animal; D005782:Gels / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D007052:Ibuprofen / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D011919:Rats, Inbred Strains; D013499:Surface Properties
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D007052:Ibuprofen