Study of the inclusion complexes formed between 4-phenylbutyrate and -, - and -cyclodextrin in solution and evaluation on their taste-masking properties

Objectives 4-Phenylbutyrate (PB), which is used in the management of urea cycle disorders, has an unpleasant taste leading to poor patient compliance. Existing PB formulations though helpful, have some limitations in their use. This study reports on attempts to mask this unpleasant taste by complexing PB with cyclodextrins (CDs) to improve patient compliance. Methods alpha, beta and gamma CD were used as CDs. Phase solubility studies, circular dichroism, H-1-NMR spectroscopy, including ROESY, and molecular modelling were used to investigate and characterize the PB-CD interactions in solution. The taste-masking effect of the CDs was evaluated using in vitro taste sensor measurements. Key findings PB interacts with alpha, beta and gamma CD in solution to form 1:1, 1:1 and 1:2 CD: PB inclusion complexes, respectively, with stability constants in the order alpha CD > beta CD > gamma CD. Taste evaluation revealed that the CDs significantly mask the taste of PB through the formation of the inclusion complexes. Notably, alpha CD masked the bitter taste of PB to 30% of the initial taste at a 1:1 molar ratio. Conclusion alpha CD significantly masks the unpleasant taste of PB in solution and can be used to formulate PB to address the limitations of existing formulations and improve patient compliance and quality of life.