1. Delivery of ionizable hydrophilic drugs based on pharmaceutical formulation of ion pairs and ionic liquids.
- Author
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Gamboa A, Schüßler N, Soto-Bustamante E, Romero-Hasler P, Meinel L, and Morales JO
- Subjects
- Animals, Drug Administration Routes, Drug Carriers chemical synthesis, Humans, Hydrophobic and Hydrophilic Interactions drug effects, Ionic Liquids chemical synthesis, Permeability drug effects, Drug Carriers administration & dosage, Drug Carriers metabolism, Drug Compounding methods, Drug Delivery Systems methods, Ionic Liquids administration & dosage, Ionic Liquids metabolism
- Abstract
New therapeutics such as antisense oligonucleotides, small interfering RNA and peptide-drug conjugates are taking great relevance in the pharmaceutical industry due to their specificity of action and their improved safety profile. However, they could present bioavailability issues due to their hydrophilic nature, such as BCS class III drugs. Therefore, the formation of ion pairs of these type of molecules allows modifying their physicochemical characteristics such as polarity and lipophilicity leading to improved permeability. By carrying out a tailored synthesis, it is possible to obtain complexes with greater stability and better performance in vitro and in vivo, where their correlation with physicochemical properties continues to be a growing field of research. Moreover, ionic liquids (IL), which are substances that melt below 100 °C, have enabled modifying various drug properties, showing promising results in vitro-in vivo, especially when they are included in suitable drug delivery systems, such as nanoparticles, microparticles, self-emulsifying drug delivery systems, and transdermal patches, among others. The drug-IL is formed from the therapeutic agent and a counterion, mainly by ionic interactions, and resulting in a wide variety of derivatives with different properties. However, the pharmaceutical field is limited to the use of some excipients or GRAS (generally recognized as safe) substances, so the search for new counterions is of great interest. In this article, we have compiled key indexes that can be obtained from databases to guide the search for suitable counterions, together with different drug delivery system strategies to choose the most appropriate formulation according to the non-parenteral route of administration selected. Intellectual property advancements in the field are also presented and analyzed., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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