Salting coefficient and thermodynamic parameters of halofantrine in electrolytes and aqueous co-solvent systems

The study was to examine the solubilization behaviour of halofantrine in electrolytes and co-solvent systems in order to select additive(s) for development of the drug into matrix and structured delivery devices. Solubility of halofantrine was determined by adding excess of the drug in 50 mL of double distilled water, electrolytes (NaCl, Na2SO4, NaNO3, Na2CO3) solution (0.01 – 0.50 M), co-solvents (10, 20, 40, 80 % v/v) of glycerol, polysorbate 80 and propylene glycol, in a 100 mL capped conical flask at 25 and 40 ºC respectively, equilibrated for 48 h and solubility determined spectrophotometrically from a validated standard curve (5-50 μg/mL, r2=0.9998) at 290 nm. Results showed that solubility of halofantrine was dependent on temperature and nature of additive(s). Only NaCl and polysorbate 80 improved solubility of halofantrine significantly with a negative Ks, ∆Gtrans and positive ∆Hºtrans, ∆Strans values at all concentration and temperature showing the spontaneity of solubilization; others salted-out halofantrine with higher Ks, ∆Gtrans, ∆Hºtrans and negative ∆Strans providing a less thermodynamically favourable environment for halofantrine solubilization. The Setschenow and thermodynamic parameters of transfer obtained could be utilized for development of halofantrine into structured devices and matrices to achieve efficient loading and entrapments that would improve solubility, absorption and bioavailability.