@conference{
author = "Verbić, Tatjana and Marković, Olivera and Pešić, Miloš and Topalović, Igor and Đurđević, Mladen and Kuentz, Martin and Avdeef, Alex and Serajuddin, Abu",
year = "2024",
abstract = "A majority of the new chemical entities (NCE) that emerged as potential drug candidates in pharmaceutical development during the past 2-3 decades are practically insoluble solids consisting of ionizable molecules [1]. Class II BCS drugs (Biopharmaceutics Classification System) exhibit poor bioavailability due to insufficient absorption in the gastrointestinal tract with slow drug release from the dosage forms and low solubility as the limiting steps for their absorption [2]. Thus, detailed and precise study of compound solubility and the possibilities to increase solubility and dissolution rate, are at the core of the development of bioavailable drug dosage forms and clinically effective pharmaceutical products that would dissolve in gastric and intestinal fluids after oral administration or not precipitate in the blood after intravenous administration. A white paper on consensus recommendations for improving data quality in equilibrium solubility measurement of ionizable drugs [3] emphasizes the importance of precise solubility measurements. As a part of solubility studies of a group of tricyclic antidepressants (TCAs) we have shown the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and solid-phase transformations on the aqueous solubility of studied drugs [4-5].
A variety of methods to increase solubility and/or dissolution rate, and thereby increase their bioavailability, have been developed. Still, most of them, like particle size reduction, salt formation, conversion to amorphous form, solid dispersion, and solubilization in lipids or lipid-surfactant mixtures have their own limitations. To mitigate some of the above limitations, a novel method of drug solubilization in aqueous media by acid–base interactions has been developed [6]. This novel approach of greatly increasing the solubility is based on interactions of a model low-soluble basic drug in an aqueous medium with acidic species that would not normally form salts with it. Although quite successful, the proposed model still needs additional work and some fine-tuning with additional low-soluble drugs to establish it as a widely accepted method for increasing solubility, dissolution rate and bioavailability of poorly water-soluble drugs. Our research team is working on it.",
publisher = "University of Novi Sad, Faculty of Sciences",
journal = "21st IUPAC International Symposium on Solubility Phenomena and Related Equilibrium Processes, Novi Sad, Serbia, September 9 – 13, 2024",
title = "Drug solubility enhancement: from buffer complexes formation to acid-base supersolubilization",
pages = "13-13"
}
