The formulation of Halofantrine as either non-solubilizing PEG 6000 or solubilizing lipid based solid dispersions: physical stability and absolute bioavailability assessment.
A non-solubilizing solid dispersion formulation (polyethylene glycol 6000) and two solubilizing solid dispersions (Vitamin E TPGS and a Gelucire 44/14/Vitamin E TPGS blend) containing the antimalarial, Halofantrine (Hf), were formulated for bioavailability assessment in fasted beagles to determine if the oral absorption of Hf can be enhanced by these delivery systems. Solid dispersions comprising varying proportions of drug to carrier were prepared by the fusion method. Whilst the non-solubilizing formulation was assessed according to its dispersion characteristics, the solubilizing solid dispersions were assessed by their ability to form microemulsions upon dispersion. Studies in fasted beagles showed that the solid dispersions afforded a five- to seven-fold improvement in absolute oral bioavailability when compared with the commercially available tablet formulation. The delivery of Hf in either a solubilizing or non-solubilizing solid dispersion did not result in significant differences in oral bioavailability. The physical stability of the solid dispersions was studied using differential scanning calorimetry and X-ray powder diffraction.
Khoo
S M
SM
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, Australia 3052.
Porter
C J
CJ
Charman
W N
WN
D000962:Antimalarials / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry* / Q000493:pharmacokinetics; D005782:Gels; D010616:Phenanthrenes / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D014810:Vitamin E / Q000737:chemistry / Q000493:pharmacokinetics
D000962:Antimalarials; D005079:Excipients; D005782:Gels; D010616:Phenanthrenes; D014810:Vitamin E; D011092:Polyethylene Glycols; C023768:halofantrine