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The present issue of ADMET and DMPK is dedicated to the IAPC-10 Meeting, which was organized as a joint event consisting of 10th World Conference on Physico-Chemical Methods in Drug Discovery and Develop¬ment and 6th World Conference on ADMET and DMPK. The meeting took place in the University of Belgrade Rectorate building, Belgrade, Republic of Serbia, September 4-6, 2023. IAPC meetings are organized as annual events in alternating European and East Asia locations. The topics covered the most advanced directions and new achievements in physico-chemical methods, which underlie almost all instrumental techniques used in the research processes in drug discovery and pharmaceutical development. Experimental determination of ADMET properties through the in vitro and in vivo assays was discussed as well as modern theoretical methods for computer-aided drug design. Ten sessions were organized, among which two special sessions: 1) Special Session on Solubility of Multi-Component Solids (Salts and Cocrystals), organized and co-chaired by Kiyohiko Sugano and Alex Avdeef, and 2) Special Session on the ADME properties and toxicity prediction by HPLC, organized and chaired by Klara Valko. Editorial

This commentary addresses data quality in equilibrium solubility measurement in aqueous solution. Broadly discussed is the “gold standard” shake-flask (SF) method used to measure equilibrium solubility of ionizable drug-like molecules as a function of pH. Many factors affecting the quality of the measurement are recognized. Case studies illustrating the analysis of both solution and solid state aspects of solubility measurement are presented. Coverage includes drug aggregation in solution (sub-micellar, micellar, complexation), use of mass spectrometry to assess aggregation in saturated solutions, solid state characterization (salts, polymorphs, cocrystals, polymorph creation by potentiometric method), solubility type (water, buffer, intrinsic), temperature, ionic strength, pH measurement, buffer issues, critical knowledge of the pKa, equilibration time (stirring and sedimentation), separating solid from saturated solution, solution handling and adsorption to untreated surfaces, solubility units, and tabulation/graphic presentation of reported data. The goal is to present cohesive recommendations that could lead to better assay design, to result in improved quality of measurements, and to impart a deeper understanding of the underlying solution chemistry in suspensions of drug solids.

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.

Editorial: Applications of biophysical techniques in drug discovery and development