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Dihydroartemisinin-cyclodextrin complexation: solubility and stability.

Muhammad Tayyab Ansari1, Ijaz Iqbal, Vivian Bruce Sunderland

  • 1Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan. Ansari.Muhammad@gmail.com

Archives of Pharmacal Research
|February 3, 2009
PubMed
Summary
This summary is machine-generated.

Hydroxypropyl-beta-cyclodextrin (HPbetaCD) complexation significantly enhances the solubility and stability of dihydroartemisinin (DHA). This formulation improves DHA

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Physical Chemistry

Background:

  • Dihydroartemisinin (DHA) is a crucial antimalarial drug, but its poor solubility and stability limit its therapeutic efficacy.
  • Developing advanced drug delivery systems is essential to overcome these limitations and improve patient outcomes.

Purpose of the Study:

  • To enhance the solubility and stability of dihydroartemisinin (DHA) through complexation with hydroxypropyl-beta-cyclodextrin (HPbetaCD).
  • To characterize the physicochemical properties and evaluate the improved stability of DHA-HPbetaCD inclusion complexes.

Main Methods:

  • Preparation and characterization of DHA-HPbetaCD inclusion complexes using techniques such as Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD).
  • Phase solubility studies were conducted in various aqueous media (water, acetate buffer, phosphate buffers) to determine complex stoichiometry and stability constants.
  • Evaluation of thermal stability, hydrolysis rates, and equilibrium solubility of both pure DHA and its HPbetaCD complexes.

Main Results:

  • DHA-HPbetaCD complexes exhibited a transition towards an amorphous state, indicated by DSC, FTIR, and XRD analyses.
  • Phase solubility studies revealed a 1:1 stoichiometric inclusion complex formation (A(L)-type).
  • Equilibrium solubility of DHA increased up to 89-fold in the presence of HPbetaCD, with specific values reaching 11.61 mg/ml in phosphate buffer (pH 7.4).
  • Complexation resulted in a 40% increase in thermal stability and a 29-fold decrease in hydrolysis rates compared to pure DHA.
  • Stability constants (K(s)) were highest in water, followed by acetate and phosphate buffers, indicating varying complex stability across different pH conditions.

Conclusions:

  • Hydroxypropyl-beta-cyclodextrin (HPbetaCD) effectively forms inclusion complexes with dihydroartemisinin (DHA), significantly improving its aqueous solubility and enhancing its thermal and hydrolytic stability.
  • The developed DHA-HPbetaCD complexes represent a promising approach for developing more stable and bioavailable DHA formulations for antimalarial therapy.