Latest developments in co-crystal formation of APIs, Nutraceuticals and AgroChems

With an increase in the size and complexity of the molecules that enter into development, companies face a larger number of compounds that are either poorly soluble, difficult to crystallize or problematic with respect to desired physicochemical properties for successful development. Over 40% of marketed drugs today have low solubility. In early discovery, 80-90% of drug candidates could fail because of solubility issues. Traditional approaches such as salt formation may no longer offer sufficient opportunities to provide a solution. Co-crystallization has emerged over the past decade as an attractive technique for modification of the physicochemical properties of organic compounds.

Within the pharmaceutical industry, co-crystals have been used for modifying the physicochemical properties of active pharmaceutical ingredients (APIs), such as altering the aqueous solubility and/or dissolution rate, increasing stability, and improving bioavailability.

Nutraceuticals are attractive as co-formers due to their ready availability, known pharmaceutical profile and natural origin, in addition to offering a dual therapy approach. Their key functional groups are robust supramolecular synthons in crystal engineering, often having antioxidants properties that can be used to impart stability issues of compounds prone to oxidation.

Co-crystallization is not only being explored in pharmaceutical industry, but also as the avenue for favorably altering the properties of agrochemical ingredients (AIs). Co-crystallization of agrochemicals is an important area of current research and holds tremendous potential for the future, as indicated by the rise in the number of co-crystals of agrochemicals. Co-crystals of agrochemicals emerged as an aid to modify physicochemical properties such as altering melting point, solubility, and dissolution rate. For example, a relatively high melting point is important in formulation processing and stability of agrochemical ingredients.

This abstract will further provide you a brief review on co-crystallization focusing on co-former selection, methods of synthesis and latest advanced technology solutions.

The first challenge faced when attempting to form a co-crystal is the selection of appropriate co-former/s. There are several co-former selection methods: supramolecular homo/hetero-synthon approach first introduced by Desiraju; Hansen solubility parameter; CSD search, retrieve and compare with existing data; COSMO approach based on the fluid-phase thermodynamics theory.

Once your chemist has a preferred list of co-formers, there are several co-crystallization methods available for experimentation: cooling co-crystallization, solvent evaporation, or a combination of the two methods; slurry; method developed by Joop ter Horst based on solubility of both compound and co-former; anti-solvent addition; ultrasound assisted co-crystallization. Screening methods based on mechano-crystallization offer a co-crystal preparation technique under completely different conditions: wet/dry co-grinding; hot melt extrusion. Last but not least, when sufficient amount of compound and resources are available, high throughput co-crystallization screening might be a choice.

Screening for co-crystals using both solution co-crystallization and mechano-crystallization seems to result in a sufficiently broad range of screening conditions to decide on the existence of a co-crystal. Nevertheless, co-crystals obtained from methods based on mechano-crystallization are more difficult to scale-up. The solution co-crystallization methods are best applied while using Crystal16® and/or Crystalline™ instrumentation. The technology brought to you by these two systems helps you to run in parallel multiple experiments in a controlled manner. The Crystal16® allows your chemists to quickly understand the effect of multiple co-crystallization methods, solvents and co-formers on your co-crystal formation with the in-situ turbidity probes. In addition, the Crystalline™ system will also answer the most pressing questions on co-crystallization with the help of particle viewing, particle size and Raman analysis. The two instruments are meant to make researchers all over the world more successful by providing advanced technology solutions for crystallization and more specifically for co-crystallization.

Webinar on Discovery of co-crystals! Did you miss this webinar? Check here to download.

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