Dissolution and physicochemical stability enhancement of artemisinin and mefloquine co-formulation via nano-confinement with mesoporous SBA-15

Colloids Surf B Biointerfaces. 2017 Jul 1:155:560-568. doi: 10.1016/j.colsurfb.2017.05.003. Epub 2017 May 2.

Abstract

The objective of this study is to enhance the dissolution rate, supersaturation and physicochemical stability of combination of two poorly water-soluble anti-malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM) and scanning electron microscope (SEM) clearly indicate the amorphization of the crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution enhancement with a burst release of more than 95% of drugs within 30min. In addition, the combination formulation exhibits a stable supersaturation enhancement by 2-fold higher than that of the untreated crystalline counterparts. ART/MQF/SBA-15 samples possess excellent physicochemical stability under 2 different moderate storage conditions for 6 months. The amorphization of ART and MFQ via nano-confinement using mesoporous SBA-15 is a potentially promising approach to enhance the solubility of poorly water-soluble anti-malarial drugs that co-formulated into a single dosage form.

Keywords: Artemisinin-based combination therapy; Dissolution rate; Excipient; Physicochemical stability; Supersaturation.

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacokinetics
  • Artemisinins / chemistry*
  • Artemisinins / pharmacokinetics
  • Chemistry, Pharmaceutical / methods*
  • Drug Liberation
  • Drug Stability
  • Mefloquine / chemistry*
  • Mefloquine / pharmacokinetics
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanostructures / chemistry
  • Nanostructures / ultrastructure
  • Particle Size
  • Porosity
  • Silicon Dioxide / chemistry*
  • Solubility
  • X-Ray Diffraction

Substances

  • Antimalarials
  • Artemisinins
  • SBA-15
  • Silicon Dioxide
  • Mefloquine