Enhanced Oral Bioavailability of Piroxicam in Rats by Hyaluronate Microspheres

• Published in: Drug development and industrial pharmacy 2007-04, Vol.33 (4), p.485-491
• Main Authors: Piao, Ming Guan, Kim, Jeong-Hoon, Kim, Jong Oh, Lyoo, Won Seok, Lee, Mann Hyung, Yong, Chul Soon, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; Bbioavailability; Biological and medical sciences; Biological Availability; Dissolution; General pharmacology; Hyaluronic Acid - chemistry; In Vitro Techniques; Male; Medical sciences; Microspheres; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Piroxicam; Piroxicam - chemistry; Piroxicam - pharmacokinetics; Polyethylene glycol; Polyethylene Glycols - chemistry; Powders; Rats; Rats, Wistar; Sodium hyaluronate; Solubility; Technology, Pharmaceutical
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639040600865223

ABSTRACTTo 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 μm 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.