Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change.
To develop a novel flurbiprofen-loaded solid dispersion without crystalline change, various flurbiprofen-loaded solid dispersions were prepared with water, sodium carboxylmethyl cellulose (Na-CMC), and Tween 80. The effect of Na-CMC and Tween 80 on aqueous solubility of flurbiprofen was investigated. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared to commercial product. Unlike conventional solid dispersion systems, the flurbiprofen-loaded solid dispersion gave a relatively rough surface and changed no crystalline form of drug. These solid dispersions were formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in changing the hydrophobic drug to hydrophilic form. Furthermore, the flurbiprofen-loaded solid dispersion at the weight ratio of flurbiprofen/Na-CMC/Tween 80 of 6/2.5/0.5 improved ~60-fold drug solubility. It gave higher AUC, T(max), and C(max) compared to commercial product. The solid dispersion improved almost 1.5-fold bioavailability of drug compared to commercial product in rats. Thus, the flurbiprofen-loaded solid dispersion would be useful to deliver poorly water-soluble flurbiprofen with enhanced bioavailability without crystalline change.
Oh
Dong Hoon
DH
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Park
Young-Joon
YJ
Kang
Jun Heok
JH
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; D002152:Calorimetry, Differential Scanning; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005480:Flurbiprofen / Q000737:chemistry* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D050866:Liquid Crystals / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013607:Tablets / Q000138:chemical synthesis / Q000737:chemistry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D004337:Drug Carriers; D011136:Polysorbates; D013607:Tablets; D014867:Water; D005480:Flurbiprofen; D002266:Carboxymethylcellulose Sodium