Partial solubility parameters of lactose, mannitol and saccharose using the modified extended Hansen method and evaporation light scattering detection

The modified extended Hansen method was tested for the first time to determ ine partial solubility parameters of non-polymeric pharmaceutical excipient s. The method was formerly tested with drug molecules, and is based upon a regression analysis of the logarithm of the mole fraction solubility of the solute against the partial solubility parameters of a series of solvents o f different chemical classes. Two monosaccharides and one disaccharide (lac tose monohydrate, saccharose and mannitol) were chosen. The solubility of t hese compounds was determined in a series of solvents ranging from nonpolar to polar and covering a wide range of the solubility parameter scale. Suga rs do not absorb at the UV-vis region, and the saturated solutions were ass ayed with a recent chromatographic technique coupled to an evaporative Ligh t scattering detector. This technique was suitable to determine the concent ration dissolved in most solvents. The modified extended Hansen method prov ided better results than the original approach. The best model was the four parameter equation, which includes the dispersion delta(d), dipolar delta( p), acidic delta(a) and basic delta(b) partial solubility parameters. The p artial solubility parameters obtained, expressed as MPa1/2, were delta(d)=1 7.6, delta(p)=28.7, delta(h)=19, delta(a)=14.5, delta(b)=12.4, delta(T)=32. 8 for lactose, delta(d)=16.2, delta(p)=24.5, delta(h)=14.6, delta(a)=8.7, d elta(b)=12.2, delta(T)=32.8 for mannitol and delta(d)=17.1, delta(p)=18.5, delta(h)=13, delta(a)=11.3, delta(b)=7.6, delta(T)=28.4 for saccharose, The high total solubility parameters delta(T) obtained agree with the polar na ture of the sugars. The dispersion parameters delta(d) are quite similar fo r the three sugars indicating that the polar delta(p) and hydrogen bonding parameters (delta(h), delta(a), delta(b)) are responsible for the variation in the total solubility parameters delta(T) obtained, as also found for dr ugs. The results suggest that the method could be extended to determine the partial solubility parameters of other non-polymeric pharmaceutical excipi ents.