β-Cyclodextrin-based ternary complexes of haloperidol and organic acids: the effect of organic acids on the drug solubility enhancement

Abstract

Haloperidol (HALO) is a weak base with very low aqueous solubility that is used as an antipsychotic drug. This study aimed to improve its solubility by forming HALO/β-cyclodextrin (β-CD)-based ternary complexes with organic acids. The solubility of HALO/β-CD binary and HALO/β-CD/organic acid ternary complexes in different media (i.e. citrate buffer pH 3 and 6) was explored. The stoichiometric ratio between the drug and β-CD was 1:1 in all complexes formed. The solubility of HALO/β-CD binary complexes significantly increased in citrate buffer pH 3 compared with citrate buffer pH 6. For the ternary complexes, HALO/β-CD/tartaric acid and HALO/β-CD/lactic acid in citrate buffer pH 3 increased HALO solubility compared with HALO/β-CD/succinic acid due to their higher unionized species. The highest stability constant and complexation efficiency values in citrate buffer pH 3 were shown by the ternary complexes with lactic acid followed by tartaric acid and succinic acid, respectively. Results indicated that lactic acid provided the greatest binding strength and solubilization efficiency for the complex.

Keywords:

• haloperidol
• β-cyclodextrin
• tartaric acid
• lactic acid
• succinic acid
• ternary complex
• solubility

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research is financially supported by the Thailand Research Fund and Mahidol University (RSA5780045 to D. Chantasart). This research is also supported in part by the Graduate Studies of Mahidol University Alumni Association (to P. Rakkaew) and the Thailand Research Fund and Faculty of Pharmacy, Mahidol University (IRG5780007).