Taste-masking mechanism of brivaracetam oral solution using cyclodextrin and sodium carboxymethyl cellulose

Brivaracetam is a novel antiepileptic medication that can be indicated for the management of epilepsy in pediatric patients over one month old. To facilitate its administration to children, an oral solution is the most suitable option. However, the inherently bitter taste of brivaracetam poses a challenge in terms of palatability, necessitating the development of a taste masking strategy for the solution. In this study, a palatable brivaracetam oral solution was prepared by meticulously screening various taste masking techniques. Then the interaction relationship between brivaracetam and pivotal excipients (sodium carboxymethyl cellulose (CMC-Na) and 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD)) within the optimized formulation was investigated by molecular dynamics simulations. It turned out that brivaracetam did not encapsulate within HP-β-CD, but instead forms a robust association through hydrogen bonding and π-stacking interactions, facilitated by the presence of CMC-Na. Further exploration through molecular docking elucidated that the optimized formulation effectively masks the bitter taste by diminishing the binding affinity of brivaracetam to bitter taste receptors. In summary, this study achieved taste masking of brivaracetam under solution conditions by investigated the interactions of brivaracetam and key excipient interactions as well as the mechanisms of taste masking of optimized formulations, providing valuable insights for similar pharmaceutical applications.