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서지반출
Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole
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  • Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole
  • Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole
저자명
Heo. Min-Young,Piao. Zong-Zhu,Kim. Tae-Wan,Cao. Qing-Ri,Kim. Ae-Ra,Lee. Beom-Jin
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2005년|28권 5호|pp.604-611 (8 pages)
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대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.