Drug Mimetic Organogelators for the Control of Concomitant Crystallization of Barbital and Thalidomide

Abstract

A strategic approach to control the polymorphism of two related drugs by introducing a drugmimetic imide functional group into the molecular weight organogelator structure is presented. This was achieved with novel aminoglutethimide-derived bis(urea) organogelators designed to form gels that act as targeted crystallization media for (±)-thalidomide and barbital. The organogelators prevent concomitant crystallization, a serious issue for drug formulation and development. This work demonstrates the potential to control concomitant crystallization with rationally designed supramolecular gelators.

Role of Mechanochemistry in Solid Form Selection and Identification of the Drug Praziquantel

“…Moreover, different polymorphs of a drug molecule can have completely different physiochemical properties such as solubility, permeability, stability, tablettability, hygroscopicity, and so on, properties that are crucial in pharmaceutical formulation development . Thus, screening for all the possible polymorphic forms of a drug and control of the polymorphic form of drug molecules is of considerable importance. − In recent years polymorph screening through mechanochemistry is becoming popular as a greener approach. , Furthermore, liquid-assisted grinding (LAG) is one of the frequently employed strategies for mechanochemical control over cocrystal, polymorphs, etc. − The stabilization of a specific polymorph of γ-aminobutyric acid by using the LAG technique with high-polarity solvents has been reported recently . Emmerling and co-workers demonstrated the formation of a metastable form III of benzamidine by using nicotinamide seeds in a LAG experiment with ethanol .…”

“…14,15 The experimental conditions affect the polymorphic outcome for a molecule; thus, understanding and controlling the experimental parameters to control the polymorphic behavior is of high scientific and industrial concern. 6,7 In this study, mechanochemistry was used to investigate the solid-state forms of racemic praziquantel (PRA) (Scheme 1). It is a chiral prescribed drug for the treatment of schistosomiasis worms.…”

Crystal Habit Modification of Metronidazole by Supramolecular Gels with Complementary Functionality

“…10 Recently, drug-mimicking LMWGs have been used to prevent concomitant crystallization. 30 Thus, structural similarity between the crystallization substrate and the gelator is potentially significant in gel phase crystallization. In the present work, we have designed bis(urea) compounds that mimic the antibiotic metronidazole as well as isomeric control gelators in order to study the outcome of the drug-mimetic gel phase crystallization of this drug substance.…”

“…Crystallization in bis­(urea) LMWGs tagged with functional groups (Scheme ) similar to a highly polymorphic drug precursor, ROY, resulted in the selective crystallization of the metastable R polymorph in contrast to the Y form obtained in solution . Recently, drug-mimicking LMWGs have been used to prevent concomitant crystallization . Thus, structural similarity between the crystallization substrate and the gelator is potentially significant in gel phase crystallization.…”

Carbocycle-Based Organogelators: Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties

“…Nowadays, the applications of organogels as soft materials are huge in several areas. They include rationally designed gels for use in drug formulation and development [1], drug release [2], medical applications [3], encapsulation and controlled flavor and fragrance release [4], pollutants removal [5], supramolecular electronics [6], materials for bioinspired catalysis [7], selective agents for anion recognition [8,9], materials for eco-friendly oil spill recovery [10][11][12] and products with manifold properties such as tissue regeneration materials, biosensors, cosmetics and lubricants, among other applications [13][14][15].…”