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

Abstract

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.

Co-Crystalline Solid Solution Affords a High-Soluble and Fast-Absorbing Form of Praziquantel

“…Notably, the solubility of PZQ is known to be independent from pH variation which might be caused by the presence of MA and TA. 27 To use the in vitro dissolution as a prediction of the in vivo performance of each sample, sink conditions were not maintained during dissolution in order to build up supersaturation, which commonly occurs under finite-volume conditions in the gastro-intestinal tract, and to allow possible events such as nucleation, crystallization, and precipitation to proceed. Hence, at time zero, a suitable amount of the sample to give 60 mg of PZQ was added to the dissolution medium.…”

Factors Influencing the Selection of Medium for Evaluating Drug Solubility and Dissolution in Bovine Milk

“…In fact, it has been suggested that the lack of attention to the use of milk as a drug delivery vehicle may be a function of the lack of attention given to the importance of post-ingestion milk digestion on the solubility and dissolution of highly lipophilic drugs (32). Along those lines, to identify effective ways to administer this antiparasitic drug to infants in tropical countries, Eason et al examined the dissolution of the poorly soluble drug, praziquantel (BCS class 2 drug) in milk or infant formula and the consequence of adding pancreatic lipase to these dissolution on drug dissolution (33). These results were compared to the solubility and in vitro dissolution of praziquantel in SGF and in simulated intestinal fed and fasted fluids (FeSSIF and FaSSIF, respectively).…”

A comparison of the detection and quantification of praziquantel via electrochemical and gas chromatography methods in freshwater and saltwater samples

“…Previous review articles can be attributed to the different approaches of detection of API. [4][5][6][7][8][9][10][11] Various methods have been developed to determine the PZQ content in different matrices, including high performance liquid chromatography (HPLC), 12,13 liquid chromatography with tandem mass spectrometry (LC-MS/MS), 14,15 near infrared spectroscopy (NIS), 16 and capillary electrophoresis (CE). 17 Electrochemical methods are also attractive since they have simpler less expensive instrumentation that can be portable.…”