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1.
J Pharm Sci ; 108(6): 2153-2161, 2019 06.
Article in English | MEDLINE | ID: mdl-30703385

ABSTRACT

We report the colloidal characterization of halofantrine (Hf)-laden soybean oil fat emulsions. Hf increased the zeta potential, at all pH values, of the fat emulsions. Concomitant with this, the isoelectric point (i.e.p.) of the emulsion increased to higher pH values. The emulsion was destabilized by a small amount of Hf; interestingly, however, this was ameliorated by increasing the amount of Hf. The particle size and polydispersity of the fat emulsion reflected this with a small Hf concentration resulting in a significant increase in both particle size and polydispersity, but less so as the Hf concentration was increased. Emulsions lost stability as the pH approached the i.e.p. and this effect was greatest for the small Hf concentration emulsions. Cryogenic transmission electron microscopy showed the presence of beading or string-like behavior leading to gross distortions of the spherical shape for highly unstable emulsions. We conclude that to maintain good stability for Hf-laden soybean oil emulsions, the pH of the emulsion should be kept away from its i.e.p, and also that the drug concentration should be maintained at a relatively high value.


Subject(s)
Antimalarials/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Phenanthrenes/chemistry , Soybean Oil/chemistry , Antimalarials/administration & dosage , Drug Compounding/methods , Drug Stability , Emulsions , Hydrogen-Ion Concentration , Isoelectric Point , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , Particle Size , Phenanthrenes/administration & dosage
2.
Int J Pharm ; 528(1-2): 524-535, 2017 Aug 07.
Article in English | MEDLINE | ID: mdl-28619452

ABSTRACT

We report on the successful incorporation of the antimalarial drug, halofantrine, into laboratory based soybean oil emulsions which were designed to mimic the commercially available parenteral fat emulsion, Intralipid®. A high pH (minimum of pH 9, preferable pH of 11) was required for the drug laden emulsion to remain stable on storage and also to resist breaking under various stresses. Ageing of lecithin samples on storage was noted to result in degradation and a decrease in pH. We argue that this is the main reason for a similar decrease in pH for lecithin based emulsions and subsequent instability in drug laden emulsions. As expected, incorporation of the drug (halofantrine) resulted in lower stability. The (intensity weighted) particle size increased from 281nm for the drug free emulsion to 550nm following a loading of 1gL-1 of halofantrine, indicative of a lowering in stability and this was reflected in a shorter shelf life. Interestingly, incorporation of even higher concentrations of drug then resulted in better stability albeit never as stable as the drug free emulsion. We also report on unusual and complex surface tension behaviour for fresh lecithin where multiple critical concentration points were observed.


Subject(s)
Emulsions/chemistry , Lecithins/chemistry , Nanoparticles/chemistry , Phenanthrenes/chemistry , Drug Stability , Hydrogen-Ion Concentration , Particle Size
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