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

Abstract

Praziquantel (PZQ) is a chiral class-II drug, and it is used as a racemate for the treatment of schistosomiasis. The knowledge of several cocrystals with dicarboxylic acids has prompted the realization of solid solutions of PZQ with both enantiomers of malic acid and tartaric acid. Here, the solid form landscape of such a six-component system has been investigated. In the process, two new cocrystals were structural-characterized and three non-stoichiometric, mixed crystal forms identified and isolated. Thermal and solubility analysis indicates a fourfold solubility advantage for the newly prepared solid solutions over the pure drug. In addition, a pharmacokinetic study was conducted in rats, which involved innovative mini-capsules for the oral administration of the solid samples. The available data indicate that the faster dissolution rate of the solid solutions translates in faster absorption of the drug and helps maintain a constant steady-state concentration.

Double Trouble: A Peculiar Case of Solid Solution Cocrystals Involving Two Chiral Compounds

“…16−19 Cappuccino et al investigated such systems looking into the cocrystallization of praziquantel with malic acid and tartaric acid. 10 In their study racemic praziquantel and an equivalent amount of malic acid and/or tartaric acid formed complete solid-solution cocrystals with a freely varying enantiomeric ratio of tartaric acid or malic acid. Furthermore, these systems allowed for an increase in solubility compared to the pure drug.…”

“…They can offer key advantages as in principle their properties can be altered by freely adjusting the proportion of the constituent components . Both cocrystal and solid solution formation are valid crystal engineering techniques to enhance physicochemical properties, with recent studies − showing how both concepts can be used to fine-tune target properties. Solid solution cocrystals involving chiral compounds often occur due to a change in the enantiomeric ratio of the chiral compound .…”

“…Solid solution cocrystals involving chiral compounds often occur due to a change in the enantiomeric ratio of the chiral compound . If the counter enantiomers are partially miscible, the term partial solid solution − is used, whereas a complete solid solution is obtained if substitution occurs over the whole range of enantiomeric ratios. − Cappuccino et al investigated such systems looking into the cocrystallization of praziquantel with malic acid and tartaric acid . In their study racemic praziquantel and an equivalent amount of malic acid and/or tartaric acid formed complete solid-solution cocrystals with a freely varying enantiomeric ratio of tartaric acid or malic acid.…”

Solid solution polymorphs afford two highly soluble co-drug forms of tolbutamide and chlorpropamide

“…2 Solid solutions are being investigated with increasing frequency as alternative pharmaceutical solid forms [3][4][5][6][7][8][9] due to the possibility of continuous control over properties such as solubility and stability. [10][11][12] Additionally, such phases are particularly advantageous in the preparation of drug-pro-drug 13 and drug-co-drug 14 forms with variable stoichiometry.…”

“…A packing similarity search with the CSD-material tool in MERCURY highlights two pairs of isomorphic crystals: 27 TBA I L (CSD refcode ZZZPUS02) 28 /CPA e (CSD refcode BEDMIG04) 29 and TBA V (CSD refcode ZZZPUS10) 30 /CPA b (CSD refcode BEDMIG01) 31 (Table S1, ESI †). Ideally, a drug-co-drug solid solution of TBA and CPA would: (i) increase solubility; 12,13 (ii) help in polymorph control 16 and (iii) provide a platform with tuneable composition for prolonged and constant plasma concentration.…”