Sodium phenylbutyrate and phenylbutyric acid complexes as strategies to mitigate taste aversion in the treatment of urea cycle diseases

BOLATTI, FG; LUCIANI GIACOBBE LC; OLIVERA, M.E.

Congreso; Reunión Anual de Sociedades de Biociencias 2023. LV Reunión Anual de la Asociación Argentina de Farmacología Experimental; 2023

Sodium Phenylbutyrate (SPB), the sodic salt of phenylbutyric acid (PBA), is an orphan drug used to treat urea cycle disorders (UCD). Treatment is expensive, lifelong and includes, in the case of adults and children, oral administration of granules and tablets in unusually high daily doses, reaching 20 g/day in patients over 20 kg. Both have a salty and bitter taste, which leads to taste aversion reactions, compromising adherence to treatment and metabolic control, mainly in the pediatric population.Eudragit E PO (EuE) is a cationic polyelectrolyte capable of ionically interacting with drugs containing acid groups, it has been described as effective for taste masking. Its sensitivity to pH allows delay in the release of the drug in the salivary environment and rapid release in gastric medium, so obtaining EuE-SPB or EuE-PBA complexes would be a valid strategy to mitigate unpleasant taste with low risk of modification of the oral absorption profile.SPB or PBA were interposed with EuE dissolved in ethanol in EuE:SPB or PBA 1:0.5 ratios; 1:0,75; 1:1 and 1:1.25 with and without preneutralization with 0.25 HCl. After drying, the materials obtained were characterized by FTIR, DSC/TGA and heatable stage microscopy in order to identify the interactions, using as a reference the precursors and their physical mixtures.EuE-PBA is formed spontaneously (even in physical mixture) in all proportions tested by ionic interaction, in addition to showing hydrophobic interactions that allow a load capacity greater than 100%. The product is presented as an amorphous semisolid difficult to handle at room temperature. In contrast, EuE-SPB is presented as an easy-to-handle powder with a load capacity of up to 50%. The presence of HCl did not produce significant differences in any case.EuE-SPB or PBA complexes would be candidates for the development of an innovative oral formulation with improved organoleptic properties.