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Complexation Equilibria: The Chelate Effect01:19

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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Complexation reactions take place when dative or coordinate covalent bonds form between metal ions and ligands. The compounds formed in these reactions are called coordination compounds. The number of bonds formed between the metal ion and the ligands is called its coordination number. Generally, most metal ions in an aqueous solution are solvated by water molecules and thus exist as aqua complexes.
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Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
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Atoms and molecules interact through bonds (or forces): intramolecular and intermolecular. The forces are electrostatic as they arise from interactions (attractive or repulsive) between charged species (permanent, partial, or temporary charges) and exist with varying strengths between ions, polar, nonpolar, and neutral molecules. The different types of intermolecular forces are ion–dipole, dipole–dipole, hydrogen bonds, and dispersion; among these, dipole–dipole, hydrogen...
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In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
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Complexation: An Interesting Pathway for Combining Two APIs at the Solid State.

Fucheng Leng1, Oleksii Shemchuk1, Koen Robeyns1

  • 1Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, 1 Place Louis Pasteur, B-1348 Louvain-La-Neuve, Belgium.

Pharmaceutics
|September 23, 2022
PubMed
Summary
This summary is machine-generated.

This study presents a novel method for creating multi-drug crystals by forming zinc salts of carboxylic Active Pharmaceutical Ingredients (APIs) to combine them with pyridine-containing APIs, improving solid form properties.

Keywords:
crystal engineeringdrug–drug complexessolid statesolubility improvement

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Area of Science:

  • Crystal engineering
  • Solid-state chemistry
  • Pharmaceutical science

Background:

  • Developing multi-drug crystalline forms is a significant challenge in crystal engineering.
  • The number of reported multi-drug solid forms is limited.
  • Combining different Active Pharmaceutical Ingredients (APIs) into single crystal forms requires innovative strategies.

Purpose of the Study:

  • To present an efficient method for co-crystallizing APIs with carboxylic groups and pyridine moieties.
  • To demonstrate the successful formation of multi-drug solid forms using this approach.
  • To highlight improvements in the physical properties of these novel solid forms.

Main Methods:

  • Formation of zinc salts from APIs containing carboxylic groups.
  • Co-crystallization of the resulting zinc salts with APIs containing pyridine moieties.
  • Characterization of the physical properties of the obtained multi-drug solid forms.

Main Results:

  • Successful combination of carboxylic APIs (as zinc salts) with pyridine-containing APIs.
  • Demonstration of an efficient approach for creating multi-drug crystalline forms.
  • Observed improvements in the physical properties of the resulting solid forms.

Conclusions:

  • Transforming carboxylic APIs into zinc salts is an effective strategy for co-crystallization with pyridine-containing APIs.
  • This method offers a viable route to expanding the library of multi-drug solid forms.
  • The developed approach yields solid forms with enhanced physical characteristics.