Enhanced oral bioavailability of piroxicam in rats by hyaluronate microspheres.
To enhance the dissolution and oral bioavailability of poorly water soluble piroxicam, the piroxicam-loaded hyaluronic microspheres were prepared with various ratios of piroxicam, sodium hyaluronate and polyethylene glycol 4000 (PEG) using a spray dryer, and their physicochemical properties such as shape, size, drug-loading efficiency and dissolution were investigated. The pharmacokinetic study of piroxicam-loaded hyaluronic micropheres in rats was then performed compared to piroxicam powder. The piroxicam-loaded hyaluronic microspheres, spherical in shape, had the geometric mean diameters of about 1.5 microm and drug loading efficiency of about 90%, irrespective of ratio of piroxicam/sodium hyaluronate/PEG. The hyaluronic microspheres containing PEG gave significantly higher dissolution rates of drug than did piroxicam powder, PEG-based solid dispersion system and hyaluronic microspheres without PEG, suggesting that the hyaluronic microsphere with sodium hyaluronate and PEG was more useful for improving the dissolution rate of poorly water soluble piroxicam. The piroxicam-loaded hyaluronic microcapsule composed of (piroxicam/sodium hyaluronate/PEG; 2: 20: 1) gave about threefold improved dissolution of drug in water for 4 h compared to piroxicam powder. It showed higher plasma concentrations of drug compared to piroxicam powder. It gave significantly higher AUC and faster Tmax of piroxicam than did piroxicam powder. In particular, the AUC of piroxicam from hyaluronic microsphere was about twofold higher than that from piroxicam powder, suggesting that it could enhance the oral bioavailability of piroxicam. Thus, the hyaluronic microsphere developed using spray-drying technique with sodium hyaluronate and PEG was a more effective oral dosage form for poorly water soluble piroxicam.
Piao
Ming Guan
MG
College of Pharmacy, Yeungnam University, Dae-Dong, Gyongsan, South Korea.
Kim
Jeong-Hoon
JH
Kim
Jong Oh
JO
Lyoo
Won Seok
WS
Lee
Mann Hyung
MH
Yong
Chul Soon
CS
Choi
Han-Gon
HG
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D006820:Hyaluronic Acid / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010894:Piroxicam / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011208:Powders; D010894:Piroxicam; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid