The significance of thermodynamic solubility in biopharmaceutical compound or drug characterization as well as the importance of having methods that accurately establish it have been extensively addressed. Nonetheless, its precise determination continues to remain a challenging task to accomplish. Even more so when the number of compounds to evaluate is high and the available amount of each compound is low, both of which are inevitable for the compound characterization during the drug development process. Except for the shake-flask method which is still considered as the ʻgold standardʼ in obtaining thermodynamic data, it is currently difficult to say that another satisfactory model which is routinely used to determine thermodynamic solubility is being applied. Therefore, this review summarizes the various experimental approaches which are based on the classical shake flask method but have yet attempted to speed up the experimental process of obtaining such data more conveniently. The most important experimental features of these approaches are provided to the reader. Some advantages and disadvantages associated with each approach are also highlighted, consequently offering a resource to those looking for the most appropriate of the approaches that have already fared well at determining the biopharmaceutically relevant drug solubility.

The RPMI 2650 and Calu-3 cell lines have been previously evaluated as models of the nasal and airway epithelial barrier, and they have demonstrated the potential to be used in drug permeation studies. However, limited data exist on the utilization of these two cell models for the assessment of nasal formulations. In our study, we tested these cell lines for the evaluation of in vitro permeation of intranasally administered drugs having a local and systemic effect from different solution- and suspension-based formulations to observe how the effects of formulations reflect on the measured in vitro drug permeability. Both models were shown to be sufficiently discriminative and able to reveal the effect of formulation compositions on drug permeability, as they demonstrated differences in the in vitro drug permeation comparable to the in vivo bioavailability. Good correlation with the available bioavailability data was also established for a limited number of drugs formulated as intranasal solutions. The investigated cell lines can be applied to the evaluation of in vitro permeation of intranasally administered drugs with a local and systemic effect from solution- and suspension-based formulations.

Herein, we report the design of a focused library of novel bacterial topoisomerase inhibitors (NBTIs) based on innovative mainly monocyclic right-hand side fragments active against DNA gyrase and Topo IV. They exhibit a very potent and wide range of antibacterial activity, even against some of the most concerning hard-to-treat pathogens for which new antibacterials are urgently needed, as reported by the WHO and CDC. NBTIs enzyme activity and whole cell potency seems to depend on the fine-tuned lipophilicity/hydrophilicity ratio that governs the permeability of those compounds through the bacterial membranes. Lipophilicity of NBTIs is apparently optimal for passing through the membrane of Gram-positive bacteria, but the higher, although not excessive lipophilicity and suitable hydrophilicity seems to determine the passage through Gram-negative bacterial membranes. However, due to the considerable hERG inhibition, which is still at least two orders of magnitude away from MICs, continued optimization is required to realize their full potential.