Multiparticulate system combining taste masking and immediate release properties for the aversive compound praziquantel.

The taste of pharmaceuticals is of particular importance as it highly affects the compliance of patients, especially for patient groups like children. In view of oral solid dosage forms, various taste masking techniques can be applied encapsulating the active pharmaceutical ingredient (API) to prevent the interaction with the taste buds. Despite a delayed drug release in saliva, an immediate drug release in gastrointestinal media is desirable for efficient drug absorption. This combinatory approach is of particular interest for poorly soluble drugs still demonstrating an aversive, bitter taste, e.g. praziquantel (PZQ). It is an anthelmintic drug of current importance for adults and children as it is the recommended therapy against schistosomiasis. First, a small scale screen was conducted to identify the most suitable polymer for a combinatorial approach of taste masking and immediate release for PZQ. Among various PZQ-polymer combinations Eudragit® E PO was chosen. Second, multiparticulate systems utilizing extrusion and spray-drying were generated comprising PZQ, Eudragit® E PO and a lipid as an additional taste masking agent. Spray-dried powders and ground extrudates showed as expected strong differences in terms of particle size distribution and morphological characteristics of the encapsulated PZQ. DSC and XRPD studies revealed the formation of an amorphous solid dispersion of PZQ after spray-drying in contrast to ground extrudates. This could be correlated to drug release studies. All formulations were subjected to non-sink dissolution studies in simulated salivary (SSF), gastric (spSGF) and intestinal (FaSSIF) media. Ground extrudates provided an efficient delayed release in SSF and immediate release and supersaturation in spSGF and FaSSIF for PZQ. Spray-dried powders revealed fast solubility kinetics and up to 5-fold supersaturation in biorelevant media, contrary to a taste masking effect. Moreover, XRPD-patterns of spray-dried powders after storage detected recrystallized PZQ resulting in varied dissolution profiles. Solid lipid extrusion combined with Eudragit® E PO enabled a promising taste masking of PZQ in SSF through encapsulation of the crystalline PZQ and further, a fast and reproducible dissolution in simulated gastric and intestinal media.

Comparative in vitro and in vivo taste assessment of liquid praziquantel formulations.

The taste of pharmaceuticals strongly affects the compliance of patients. This study investigated the applicability of the electronic tongue and rodent brief-access taste aversion (BATA) model for the bitter compound praziquantel (PZQ) and taste masked liquid formulations for PZQ. In a comparative study maltodextrin (MD) Kleptose® linecaps 17 was selected as an alternative taste masking agent to two cyclodextrins; hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-ß-CD). A phase solubility study showed the highest affinity and solubilization capabilities for SBE-ß-CD over HP-ß-CD and MD, suggesting the highest taste masking ability for SBE-ß-CD. No reliable results were achieved for PZQ with the Insent electronic tongue. Thus this system was not used for further evaluation of solutions with MD and CDs to confirm the results of the solubility study. In contrast the BATA model demonstrated conclusive responses for the aversiveness of PZQ. The concentration of PZQ inhibiting 50% of water lick numbers (called IC50 value) was 0.06mg/ml. In contrast to the phase solubility study, the MD enabled an equal taste masking effect in vivo in comparison to both CDs. Moreover HP-ß-CD showed superior taste masking capabilities for PZQ compared to SBE-ß-CD as the SBE-ß-CD itself was less acceptable for the rodents than HP-ß-CD. In conclusion, the BATA model was identified as a more efficient taste assessment tool for the pure PZQ and liquid formulations in contrast to the electronic tongue and the phase solubility study.