Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present.

Automated summary

Praziquantel, a poorly water-soluble drug used to treat parasitic infections, shows slow dissolution in milk and biorelevant media compared to pharmacopoeial-recommended medium, despite reported positive food effect. This study reexamines praziquantel dissolution in biorelevant media and milk, incorporating digestion to mimic gastrointestinal conditions. The presence of sodium lauryl sulfate (SLS) in dissolution media promotes drug dissolution, and significant dissolution in milk is observed during digestion. This suggests potential use of milk to enhance oral bioavailability of praziquantel, and inclusion of digestion step in in vitro dissolution testing to reflect positive food effect in the presence of lipids.