Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability.
To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.
Park
Young-Joon
YJ
Research Center, Samil Pharmaceutical Co. Ltd., Anyang, 431-060, Korea.
Xuan
Jing Ji
JJ
Oh
Dong Hoon
DH
Balakrishnan
Prabagar
P
Yang
Ho-Joon
HJ
Yeo
Woo Hyun
WH
Lee
Mi-Kyung
MK
Choi
Han-Gon
HG
Yong
Chul Soon
CS
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D019343:Citric Acid / Q000737:chemistry; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D057927:Hydrophobic and Hydrophilic Interactions; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
D000935:Antifungal Agents; D004337:Drug Carriers; D020442:Poloxamer; D019343:Citric Acid; D017964:Itraconazole; D011205:Povidone