Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier.
Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol® HS15 exhibited superior stabilizing effect to Cremophor® RH40 and Kollidon® 30. The physical state of the dispersed curcumin in the polymer matrix was characterized by differential scanning calorimetry and X-ray diffraction studies. SD preparation transformed curcumin into amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in aqueous medium. In vitro drug release in pH 6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1h. Pharmacokinetic study of the solid dispersion formulation in rat showed that bioavailability of the drug was significantly improved as compared to pure curcumin. SD containing 1:10 ratio of drug and Solutol® HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months.
BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, Republic of Korea.
Sang-Wan
SW
Seo
Hyo-Kyung
HK
Han
Myung-Kwan
MK
Chun
Hoo-Kyun
HK
Choi
D000818:Animals; D001682:Biological Availability; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
D004337:Drug Carriers; D013229:Stearic Acids; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D003474:Curcumin