A Review of Coformer Utilization in Multicomponent Crystal Formation

Abstract

Most recently discovered active pharmaceutical molecules and market-approved medicines are poorly soluble in water, resulting in limited drug bioavailability and therapeutic effectiveness. The application of coformers in a multicomponent crystal method is one possible strategy to modulate a drug’s solubility. A multicomponent crystal is a solid phase formed when several molecules of different substances crystallize in a crystal lattice with a certain stoichiometric ratio. The goal of this review paper is to comprehensively describe the application of coformers in the formation of multicomponent crystals as solutions for pharmaceutically active ingredients with limited solubility. Owing to their benefits including improved physicochemical profile of pharmaceutically active ingredients, multicomponent crystal methods are predicted to become increasingly prevalent in the development of active drug ingredients in the future

Crystal Structures and Physicochemical Properties of 3-Chloro-4-hydroxyphenylacetic Acid Salts with Amines

“…Two mass loss steps were observed for (CHPAA 2− )(2DEA + ). The first mass loss of 10.5% observed at 315 K is due to the loss of 1 2 DEA, and the second mass loss at 396 K for the remaining DEA overlaps with the decomposition of CHPAA. The DSC curve of (CHPAA 2− )(2DEA + ) shows two endothermic peaks.…”

“…Multicomponent crystals are important in the pharmaceutical industry as the formation of new solid forms can improve the physicochemical properties of active pharmaceutical ingredients [1,2]. The choice of co-crystal formers can affect properties such as the solubility, hygroscopicity and compaction of the resultant pharmaceutical co-crystals and salts.…”

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation

“…The attachments containing the disks were immersed into 500 mL of phosphate buffer, pH 6.8, medium preheated at 37.0 ± 0.5 °C with the metallic rod rotating at 100 rpm. At specific time intervals (5,10,15,20,30,45, and 60 min), 5 mL of dissolution medium was withdrawn and immediately filtered through a 0.45 μm syringe filter before the quantification of dissolved DTIC by LC-UV.…”

Improving the Solubility of Fenofibric Acid via Multicomponent Crystal Formation with Theobromine Coformer

“…Theobromine has a hydrogen bond donor and is an important acceptor group for multicomponent crystal formation. Theobromine has been used as a coformer in crystal engineering of several medicinal substances such as sulfasalazine, 13 glimepiride, 14 daidzein, 15 and has proven to increase solubility. This research aims to study the effect of multicomponent crystal formation of fenofibric acid and theobromine as coformer (Figure 1) on physicochemical properties and its effect on solubility.…”