Structural, Physicochemical, and Biopharmaceutical Properties of Cocrystals with RS- and R-Praziquantel─Generation and Prolongation of the Supersaturation State in the Presence of Cellulosic Polymers

Two novel cocrystals of the pharmaceutically active enantiomer R- Praziquantel ( R -PZQ) were formed with glutaric acid ( R- PZQ/GA) and succinic acid ( R- PZQ/SA) in a 1:1 stoichiometric ratio by liquid-assisted mechanical grinding. The characterization of the cocrystals by structural and physicochemical methods revealed properties distinct from the cocrystal analogues with racemic PZQ, i.e., RS- PZQ/GA and RS- PZQ/SA, reported previously in the literature. However, all four cocrystals exhibit improved intrinsic dissolution rates in a medium simulating the physiological conditions of the gastric fluid (pH 1.2) compared to the solid phases of the pristine drug ( R- PZQ·0.5H 2 O and RS- PZQ). Nonsink powder dissolution tests showed that the cocrystals with R - and RS -PZQ can generate transient supersaturated solutions with solubility advantages of 1.3- to 2.2-fold compared to the pristine drugs. In the presence of predissolved hydrophobic polymers such as MC60HG and HPC 80,000, the supersaturation state is prolonged for 20–30 min providing solubility advantages of up to 2.7-fold and an even larger advantage compared to the pristine forms of Praziquantel.