Novel non-acidic formulations of haloperidol complexed with beta-cyclodextrin derivatives.

Haloperidol (Hal), a highly hydrophobic drug, was complexed with two beta-cyclodextrin (beta-CD) derivatives. Hal solubility was increased 20-fold in the presence of a 10-fold excess of methyl beta-CD (Me beta-CD) and 12-fold in the presence of a 10-fold excess of 2-hydroxypropyl beta-CD (HP beta-CD). The stoichiometries and stability constants of Hal-Me beta-CD (1:1 and 2345 M-1 at 27 degrees C) and Hal-HP beta-CD (1:1 and 2112 M-1 at 27 degrees C) complexes were calculated by the continuous variation and phase solubility methods respectively. Differential scanning calorimetry and 1H-NMR were used to confirm the formation of inclusion complexes. Moreover, the enthalpy and entropy of the complexation process were calculated for both complexes in order to obtain such information as the main 'driving force' and whether or not complex formation is thermodynamically favoured. This was achieved by monitoring the isothermic solubility lines at various temperatures.