Development of a Cucurbituril Suspension-Based Dosage Formulation and its Ability to Taste Mask Paracetamol

Medication non-adherence as a result of aversion to the bitter taste of active pharmaceutical ingredients and/or an inability to swallow solid dosage forms presents a challenge to the optimal use of medicines. The aims of this study were to examine the interactions of cucurbit[n]urils (CB[n]; n = 6, 7, 8) with paracetamol, and CB[7] with common pharmaceutical excipients, to design an effective oral suspension dosage formulation with CB[n]s as a potential taste masking excipient, and to assess the ability of CB[7] to reduce the bitter taste of paracetamol in rats. 1H NMR spectrometry was used to investigate the ability of CB[6], CB[7], and CB[8] to form host‒guest complexes with paracetamol, and interactions between CB[7] and common pharmaceutical excipients. Cucurbit[7]uril was able to form host‒guest complexes with paracetamol, but there was no binding between paracetamol and CB[6] and CB[8] most likely due to the salt (NaCl) used to dissolve the macrocycles. The only excipient found to interact with CB[7] was sodium propionate. a pharmaceutical suspension formulation based on CB[6] was designed to create a uniform product that was syringeable, easy to suspend and resuspend, and did not cake upon standing. The most stable formulation contained: CB[6] (171 mg/mL), propylene glycol (10–20% w/v), xanthan gum (0.05–0.1% w/v), potassium sorbate (0.2% w/v), sodium metabisulfite (0.25–0.5% w/v), and the dosage formulation made to volume using carboxymethyl cellulose (low viscosity) 1%–1.5% w/v. From the taste masking experiments, it was found that CB[7] was not effective in reducing the bitter taste of paracetamol, as the rats had a significantly lower preference for samples containing CB[7] and paracetamol compared with samples containing paracetamol alone