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Dihydroartemisinin-cyclodextrin complexation: solubility and stability.
Arch Pharm Res. 2009 Jan; 32(1):155-65.AP

Abstract

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-beta-cyclodextrin (HPbetaCD) 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-HPbetaCD 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 HPbetaCD concentration. DHA-HPbetaCD complexes showed an 89-fold increase in solubility compared to DHA. Solubilities of complexes containing 275.1 mM HPbetaCD 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 HPbetaCD, and it was stronger in complexes prepared in water than in buffers. However, the AH values were higher in buffer than water. DHA-HPbetaCD complexes prepared using commercial (untreated) or recrystallized DHA (no detectable impurity) showed a 40% increase in thermal stability (50 degrees 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, HPbetaCD complexation with recrystalized DHA increases DHA solubility and stability.

Authors+Show Affiliations

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan. Ansari.Muhammad@gmail.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19183889

Citation

Ansari, Muhammad Tayyab, et al. "Dihydroartemisinin-cyclodextrin Complexation: Solubility and Stability." Archives of Pharmacal Research, vol. 32, no. 1, 2009, pp. 155-65.
Ansari MT, Iqbal I, Sunderland VB. Dihydroartemisinin-cyclodextrin complexation: solubility and stability. Arch Pharm Res. 2009;32(1):155-65.
Ansari, M. T., Iqbal, I., & Sunderland, V. B. (2009). Dihydroartemisinin-cyclodextrin complexation: solubility and stability. Archives of Pharmacal Research, 32(1), 155-65. https://doi.org/10.1007/s12272-009-1130-4
Ansari MT, Iqbal I, Sunderland VB. Dihydroartemisinin-cyclodextrin Complexation: Solubility and Stability. Arch Pharm Res. 2009;32(1):155-65. PubMed PMID: 19183889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydroartemisinin-cyclodextrin complexation: solubility and stability. AU - Ansari,Muhammad Tayyab, AU - Iqbal,Ijaz, AU - Sunderland,Vivian Bruce, Y1 - 2009/01/29/ PY - 2008/11/03/received PY - 2008/12/31/accepted PY - 2008/12/30/revised PY - 2009/2/3/entrez PY - 2009/2/3/pubmed PY - 2009/2/28/medline SP - 155 EP - 65 JF - Archives of pharmacal research JO - Arch Pharm Res VL - 32 IS - 1 N2 - 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-beta-cyclodextrin (HPbetaCD) 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-HPbetaCD 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 HPbetaCD concentration. DHA-HPbetaCD complexes showed an 89-fold increase in solubility compared to DHA. Solubilities of complexes containing 275.1 mM HPbetaCD 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 HPbetaCD, and it was stronger in complexes prepared in water than in buffers. However, the AH values were higher in buffer than water. DHA-HPbetaCD complexes prepared using commercial (untreated) or recrystallized DHA (no detectable impurity) showed a 40% increase in thermal stability (50 degrees 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, HPbetaCD complexation with recrystalized DHA increases DHA solubility and stability. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/19183889/Dihydroartemisinin_cyclodextrin_complexation:_solubility_and_stability_ L2 - https://dx.doi.org/10.1007/s12272-009-1130-4 DB - PRIME DP - Unbound Medicine ER -