Cavity-containing supramolecular gels as a crystallization tool for hydrophobic pharmaceuticals

Abstract

We present two approaches to low-molecular-weight supramolecular gels bearing hydrophobic cavities based on calixarene-containing building blocks. Gels are formed by a calixarene based tetrahydrazide gelator or a co-gel of a calixarene diammonium salt and a bis-crown ether. The calixarene hydrophobic cavity enables the complexation of hydrophobic drug molecules in a generic fashion thus providing an anchor site on the surface of the gel fibre to initiate drug crystal nucleation and growth. This technique potentially represents a route to growth of hard-to-nucleate polymorphic modifications. The co-gel comprising two components holding together by non-covalent ammonium-crown ether interaction can be easily switched back to the sol state by adding competitive binding cations.

Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

“…The use of gels in the pharmaceutical field has been studied by several groups, especially for encapsulation and drug delivery applications since gels can be swelled in certain media for the easy release of entrapped drug crystals [ 108 , 109 , 110 ]. More recently, crystallization of APIs within gel networks has gained traction due to control of over both surface geometry and surface chemistry [ 105 , 111 , 112 ]. While some gels are a type of cross-linked polymer networks, they can also be formed using lower molecular weight organics and even inorganic materials that attract through physical interactions.…”

“…Heterogeneous crystallization from such materials has already been discussed but agglomerates can also present with surface roughness, where features act as micropores and have the further advantage of confinement. The differences in surface morphology result in access to crystal faces that would otherwise not be possible [ 104 , 111 ], which results in additional control over the crystallization process compared to using a flatter surface such as a film or single crystal.…”

Luminescent Supramolecular Heterometallic Macrocycles and their Encapsulation on Cholate Gels

“…These interactions enable the reversible formation of large self‐assemblies or supramolecular polymers, forming a solid‐like network (minor component) which is able to entrap either an organic solvent or water (major component) through surface tension or capillary forces . Due to their particular properties, in the last decades the use of supramolecular gels has been studied in a wide range of applications such as drug delivery and tissue engineering,, crystallization of pharmaceuticals, luminescent materials, reaction vessels and reusable catalysts, and pollutant removal, among others.…”

Peptide-based ambidextrous bifunctional gelator: applications in oil spill recovery and removal of toxic organic dyes for waste water management

“…Low molecular weight gelators [1][2][3][4][5][6][7][8][9][10][11][12] are important systems exploiting molecular assembly [13 -17] with many fascinating applications for modern society [18][19][20]. In this category, peptide-and amino acid-based gels [21 -34] are important classes of materials owing to their bioavailability and biocompatibility [24,35].…”