Preparation and Characterization of Solid Dispersions of Artemether by Freeze-Dried Method

Biomed Res Int. 2015:2015:109563. doi: 10.1155/2015/109563. Epub 2015 May 17.

Abstract

Solid dispersions of artemether and polyethylene glycol 6000 (PEG6000) were prepared in ratio 12 : 88 (group-1). Self-emulsified solid dispersions of artemether were prepared by using polyethylene glycol 6000, Cremophor-A25, olive oil, Transcutol, and hydroxypropyl methylcellulose (HPMC) in ratio 12 : 75 : 5 : 4 : 2 : 2, respectively (group-2). In third group, only Cremophor-A25 was replaced with Poloxamer 188 compared to group-2. The solid dispersions and self-emulsified solid dispersions were prepared by physical and freeze dried methods, respectively. All samples were characterized by X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimeter, scanning electron microscopy, and solubility, dissolution, and stability studies. X-ray diffraction pattern revealed artemether complete crystalline, whereas physical mixture and freeze-dried mixture of all three groups showed reduced peak intensities. In attenuated total reflectance Fourier transform infrared spectroscopy spectra, C-H stretching vibrations of artemether were masked in all prepared samples, while C-H stretching vibrations were representative of polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188. Differential scanning calorimetry showed decreased melting endotherm and increased enthalpy change (ΔH) in both physical mixture and freeze-dried mixtures of all groups. Scanning electron microscopy of freeze-dried mixtures of all samples showed glassy appearance, size reduction, and embedment, while their physical mixture showed size reduction and embedment of artemether by excipients. In group-1, solubility was improved up to 15 times, whereas group-2 showed up to 121 times increase but, in group-3, when Poloxamer 188 was used instead of Cremophor-A25, solubility of freeze-dried mixtures was increased up to 135 times. In fasted state simulated gastric fluid at pH 1.6, the dissolution of physical mixture was increased up to 12 times and freeze-dried mixtures up to 15 times. The stability of artemether was substantially enhanced in freeze-dried mixtures by using polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188 of self-emulsified solid dispersions of artemether in Hank's balanced salt solution at pH 7.4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artemether
  • Artemisinins / chemistry*
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical*
  • Drug Carriers / chemistry*
  • Emulsions / chemistry
  • Freeze Drying
  • Hypromellose Derivatives / chemistry
  • Poloxamer / chemistry
  • Polyethylene Glycols / chemistry
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Artemisinins
  • Drug Carriers
  • Emulsions
  • Poloxamer
  • cremophor
  • Hypromellose Derivatives
  • Polyethylene Glycols
  • Artemether