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

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

Pharmaceutical Development and Technology 23(7): 715-722

ISSN/ISBN: 1083-7450

PMID: 28627267

DOI: 10.1080/10837450.2017.1344993

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.

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Accession: 059572895

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