Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications

Abstract

Pharmaceutical co-crystals are novel class of pharmaceutical substances, which possess an apparent probability of advancement of polished physical properties offering stable and patentable solid forms. These multi-component crystalline forms influence pertinent physicochemical parameters like solubility, dissolution rate, chemical stability, physical stability, etc. which in turn result in the materials with superior properties to those of the free drug. Co-crystallization is a process by which the molecular interactions can be altered to optimize the drug properties. Co-crystals comprise a multicomponent system of active pharmaceutical ingredient (API) with a stoichiometric amount of a pharmaceutically acceptable coformer incorporated in the crystal lattice. By manufacturing pharmaceutical co-crystals, the physicochemical properties of a drug can be improved thus multicomponent crystalline materials have received renewed interest in the current scenario due to the easy administration in the pharmaceutical industry. There is an immense amount of literature available on co-crystals. However, there is a lack of an exhaustive review on a selection of coformers and regulations on co-crystals. The review has made an attempt to bridge this gap. The review also describes the methods used to prepare co-crystals with their characterization. Brief description on the pharmaceutical applications of co-crystals has also been incorporated here. Efforts are made to include reported works on co-crystals, which further help to understand the concept of co-crystals in depth.

Study on the Effect of Polymer Excipients on the Dispersibility, Interaction, Solubility, and Scavenging Reactive Oxygen Species of Myricetin Solid Dispersion: Experiment and Molecular Simulation

“… 3 , 4 For targeting this drawback, it is significant to apply related technologies to improve the solubility of drugs in water. The common methods include solid dispersion loading, 5 prodrug synthesis, 6 cyclodextrin complexation, 7 phospholipid complexation, 8 polymerization micellar loading, 9 nanoparticle delivery, 10 cocrystallization, 11 etc. At present, the solid dispersion technology has been widely used as a method of drug solubilization.…”

Stability of Pharmaceutical Co-Crystals at Humid Conditions Can Be Predicted

“…The CC might have significantly improved physical properties compared to the pure API, such as increased aqueous solubility or stability [ 2 , 3 ]. Due to the change in the regulatory framework of authorities such as the Food and Drug Administration (FDA) [ 4 ] regarding the intellectual property and impact on the product-lifecycle-management, CCs have gained increasing interest in recent years [ 5 ]. An important factor for the approval of CCs is their stability against environmental changes or stress conditions [ 6 , 7 , 8 ].…”

The Impact of Halogen Substituents on the Synthesis and Structure of Co-Crystals of Pyridine Amides

“…Most of these efforts have been in the area of basic science, with the goal of establishing guidelines for how different molecules and functional groups recognize and bind to each other via non-covalent interactions [12]. Such insights can enable forays into applied materials science by applying co-crystal technology to the synthesis of new solid forms of pharmaceutically relevant compounds [13,14], agrochemicals [15,16], energetic materials [17,18], and other high-value solids [19]. In order to learn more about competing molecular-recognition events in supramolecular assembly, we previously examined the outcomes of co-crystallization of N-(pyridin-2-yl)nicotinamide and about competing molecular-recognition events in supramolecular assembly, we previously examined the outcomes of co-crystallization of N- (pyridin-2-yl)nicotinamide and N-(pyridin-2-yl)isonicotinamide with di-carboxylic acids and identified reliable recognition events between both the N2(py) and N1(py)-NH sites of the target molecules to the dicarboxylic acids.…”