Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

Abstract

Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.

Keywords: amorphous solid dispersions; hot-melt extrusion; interpolyelectrolyte complex; polyelectrolyte matrices.

Figure 1

Energetic state pyramid of the crystalline phase, amorphous solid dispersion, and amorphous phase, where μ denotes the chemical potential. (Adapted with permission from [33], published by John Wiley & Sons, Inc., 2016).

Figure 2

Reported processes for preparation of polyelectrolyte-drug formulations. (Adapted with permission from [46], Elsevier, Inc., 2017).

Figure 3

Hydrogen bonding patterns of propranolol/Eudragit L100 (PRP/L100) and diphenhydramine/L100-55 calculated by Gaussian 09. (Adapted with permission from [73], Elsevier, Inc., 2017).

Figure 4

Synergistic role of Eudragit and HPMC in dissolution enhancement. (Adapted with permission from [104], Elsevier, Inc., 2017).

Figure 5

SEM images of (A) amorphous Eudragit EPO, (B) spherical Eudragit L100, (C) amorphous stoichiometric IPEC of EPO/L100. (Adapted with permission from [119], Scientific Electronic Library Online, Brazil, 2018).

Figure 6

Molecular mechanic simulations of the synthetic process of NaCMC/E100 IPEC. (a) initial stage of mixing, (b) after 1 h, (c) breaking point, (d) final formation of the IPEC. (Adapted with permission from [122], MDPI, 2013).

Figure 7

Schematic interpretation of phenytoin dissolution and supersaturated solution formed by phenytoin: Eudragit EPO: saccharin ASDs. (Adapted with permission from [126], Elsevier, Inc., 2018).

Figure 8

Electrostatic stabilization of amorphous solid dispersions of polyelectrolytes under controlled moisture and temperature conditions. (Adapted with permission from [86], American Chemical Society, 2013).