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Dihydroartemisinin-cyclodextrin Complexation: Solubility and Stability
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  • Dihydroartemisinin-cyclodextrin Complexation: Solubility and Stability
  • Dihydroartemisinin-cyclodextrin Complexation: Solubility and Stability
저자명
Ansari. Muhammad Tayyab,Iqbal. Ijaz,Sunderland. Vivian Bruce
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2009년|32권 1호|pp.155-165 (11 pages)
발행정보
대한약학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Dihydroartemisinin (DHA) is a major metabolite of artemisinin and its derivatives, including arteether, artemether, and artesunate. To improve the solubility and stability of poorly soluble DHA, we prepared inclusion complexes with hydroxypropyl-$eta$-cyclodextrin ($HP{eta}CD$) and recrystalized DHA to study its thermal stability. The complexes were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), thermal stability, phase, and equilibrium solubility studies. Pure DHA was crystalline and remained crystalline after recrystallization, but its unit cell dimensions changed as exhibited by XRD. DHA-$HP{eta}CD$ complexes showed a phase transitions towards amorphous in DSC thermograms, FTIR spectra, and XRD patterns. The phase solubility profiles of complexes prepared in water, acetate buffer, and phosphate buffers were classified as $A_L$-type, indicating the formation of a 1:1 stoichiometric inclusion complex. The equilibrium solubility of DHA was enhanced as a function of $HP{eta}CD$ concentration. DHA-$HP{eta}CD$ complexes showed an 89-fold increase in solubility compared to DHA. Solubilities of complexes containing 275.1 mM $HP{eta}CD$ in water, acetate buffer (pH 3.0), and phosphate buffer (pH 3.0 and 7.4) were 10.04, 7.96, 6.30, and 11.61 mg/ml, respectively. Hydrogen bonding was found between DHA and $HP{eta}CD$, and it was stronger in complexes prepared in water than in buffers. However, the $ddot{A}H$ values were higher in buffer than water. DHA-$HP{eta}CD$ complexes prepared using commercial (untreated) or recrystallized DHA (no detectable impurity) showed a 40% increase in thermal stability ($50^{circ}C$) and a 29-fold decrease in hydrolysis rates compared with DHA. The rank order of stability constants ($K_s$) was: water, acetate buffer (pH 3.0), phosphate buffer (pH 3.0), and phosphate buffer (pH 7.4). Thus, $HP{eta}CD$ complexation with recrystalized DHA increases DHA solubility and stability.