Cyclodextrin-mediated Enhancement of Haloperidol Solubility: Physicochemical Studies and In Vivo Investigation Using...

This study aims to evaluate the ability of various cyclodextrins (CDs) to enhance the aqueous solubility of haloperidol (HAL), through the formation of inclusion complexes. It also investigates the pharmacological activity of CD/HAL complexes using a planaria model.

Inclusion complexes were prepared using α-CD, β-CD, methyl-β-CD, hydroxypropyl-β-CD and γ-CD. The solubility of HAL in the presence of CDs was assessed, and the stoichiometry of the complexes was determined using Job's method. Physicochemical interactions between HAL and CDs were characterized by nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The in vivo pharmacological activity was tested in planaria worms following exposure to HAL in the presence or absence of CDs.

HAL's aqueous solubility was significantly enhanced in the presence of α-CD, methyl-β-CD, and hydroxypropyl-β-CD, while γ-CD showed no effect. Only modest solubility improvements were observed with increasing β-CD concentrations up to 8 mg/mL. Stoichiometric analysis confirmed a 1:1 ratio of HAL to CD in the inclusion complexes. In vivo studies demonstrated that HAL reduced planaria mobility, mimicking cataleptic effects seen in mammals, whereas the presence of CDs reduced this pharmacological effect.

Cyclodextrins, particularly α-CD, methyl-β-CD, and hydroxypropyl-β-CD, effectively enhance the solubility of haloperidol by forming 1:1 inclusion complexes. The reduction in haloperidol-induced behavioral changes in planaria by CDs suggests a potential impact on drug bioavailability and supports the use of planaria as a simple in vivo model for screening neuroactive compounds and formulations.