Intermolecular Interactions between Drugs and Aminoalkyl Methacrylate Copolymer in Solution to Enhance the Concentration of Poorly Water-Soluble Drugs

Abstract

An aminoalkyl methacrylate copolymer, Eudragit ® E (EUD-E), has gained tremendous attention as a solid dispersion carrier because it efficiently stabilizes drugs in the amorphous state. Furthermore, EUD-E remarkably enhances drug dissolution in water. This review focuses on the interaction between drugs and EUD-E in solution, which contributes to the enhancement of drug concentration. Studies examining interactions between acidic drugs and EUD-E in organic solvents have revealed that the interaction occurs predominantly by electrostatic interaction, including hydrogen bonding and dipolar interactions. Other studies on interactions in aqueous solution found evidence for strong electrostatic interactions between acidic drugs and EUD-E in ion exchange experiments. 1 H-NMR studies using high-resolution magic-angle spinning, nuclear Overhauser effect spectroscopy, diffusion, and relaxation time measurements successfully identified the interaction site and strength in aqueous solution. Hydrophobic and ionic interactions occurred between drugs and EUD-E. The conformation of EUD-E, which was affected by the ionic strength and pH of the aqueous media, also influenced the interaction. The knowledge discussed in this review will be helpful in designing solid dispersion formulations with EUD-E, which will efficiently enhance drug concentration and subsequent absorption into the body.

Additives for Kinetic Hydrate Inhibitor Formulations to Avoid Polymer Fouling at High Injection Temperatures: Part 3. Experimental Studies with Added Polymers

“…These are really polymeric dispersants that have been designed to enhance their dispersibility of various drugs to make them more accessible to adsorption in the body. An example is a class of methacrylate-based terpolymers mostly made up of three methacrylate monomers, butyl methacrylate, 2-dimethylaminoethyl methacrylate, and methyl methacrylate. , A methacrylate terpolymer polymer from this series was used in our study. By itself it is soluble in water or brines at pH 5–6 or less, which will make it slightly cationic.…”

“…An example is a class of methacrylate-based terpolymers mostly made up of three methacrylate monomers, butyl methacrylate, 2-dimethylaminoethyl methacrylate, and methyl methacrylate. 40,41 A methacrylate terpolymer polymer from this series was used in our study. By itself it is soluble in water or brines at pH 5−6 or less, which will make it slightly cationic.…”

Additives for Kinetic Hydrate Inhibitor Formulations To Avoid Polymer Fouling at High Injection Temperatures: Part 1. A Review of Possible Methods

“…One example is a class of terpolymers mostly consisting of three methacrylate monomers: butyl methacrylate, 2-dimethylaminoethyl methacrylate, and methyl methacrylate (see Figure ). , The polymer by itself is soluble in water or brines at pH values of 5–6 or less. This polymer is particularly helpful at solubilization acidic drugs via ionic interactions (e.g., protonated amine moieties) and by multiple hydrophobic contacts with the polymeric side chains. , A few nonacidic hydrophobic drugs have also been solubilized using this polymer. , Therefore, by judicial choice of the correct functional groups, it should be possible to help solubilize KHIs, which are predominantly polyamides.…”

“…One example is a class of terpolymers mostly consisting of three methacrylate monomers: butyl methacrylate, 2-dimethylaminoethyl methacrylate, and methyl methacrylate (see Figure 9). 123,124 The polymer by itself is soluble in water or brines at pH values of 5−6 or less. This polymer is particularly helpful at solubilization acidic drugs via ionic interactions (e.g., protonated amine moieties) and by multiple hydrophobic contacts with the polymeric side chains.…”

Nanostructure and Molecular-Level Characterization of Aminoalkyl Methacrylate Copolymer and the Impact on Drug Solubilization Ability

“…EUD-E is widely used for moisture protection coating and taste masking in pharmaceutical formulation. 20 Furthermore, because EUD-E has strong crystallization inhibition 21 and drug solubilization abilities, 22,23 its application as a polymeric carrier of solid dispersion has attracted great attention. We reported that EUD-E significantly improved the stability of mefenamic acid (MFA) in its amorphous state in solid dispersion according to the ionic interaction between MFA and EUD-E. 24 Moreover, the maintenance of a high MFA concentration after dispersing the solid dispersion into water and subsequent bioavailability enhancement in vivo study using rats were demonstrated.…”