Co-crystals of 3-Iodopropynyl butylcarbamate (IPBC)
The present invention relates to a method for improving enhanced physical and chemical proprieties of 3-iodopropynyl butylcarbamate (IPBC) through its co-crystalisation with other molecules.
The invention is particularly intriguing because “at the same time, it relates both to the IPBC, a highly versatile molecule with an important economic value, and to the synthesis of co-crystals, one of the most innovative topic in Solid State Chemistry of the last years. The match of these two topics has been exploited in an innovative technology, able to give new horizons to a molecule that has been in the market from a long time” (Prof. Giancarlo Terraneo, one of the inventors).
IPBC is a biocide, largely used as preservative, fungicide and inhibitor against algae proliferation in industrial formulations such as paints, coatings and wood preservative formulations. It is also used in metalworking fluids, in the preservation of polymer-based products and in the preservation of personal care products and cosmetics. However, IPBC shows several drawbacks that make its use difficult in common manufacturing processes, namely a low melting point (67°C), a poor water solubility, and a high cohesiveness of powders that compromises its use in automated handling devices during manufacturing processes.
To address these drawbacks a group of researchers from the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” of Politecnico di Milano, has developed an innovative solution, which includes the synthesis of co-crystals where the active pharmaceutical ingredient is assembled with another molecule (named co-crystal former). The result is a new molecular entity, the co-crystal which displays enhanced physical and chemical properties such as higher soluble, thermodynamically more stable and more easy to handle than the pure IPBC crystalline form. Due to these properties, the co-crystals can be used alternatively to IPBC, assuring better performances in the manufacturing processes and in the preparation of formulates.
In the case of IPBC, the co-crystals can be formed by a supramolecular approach involving the assembly of IPBC with selected chemical species called co-crystal formers, which are able to establish non-covalent interactions involving the iodine atom (halogen bond, XB) present in the molecular structure of IPBC. The co-crystal formers used in the invention are: organic bases, in particular aliphatic amines or aromatic heterocyclic derivatives containing at least one basic nitrogen atom; halides; phosphates; and carboxylates. Other co-crystallisation agents can be an organic or inorganic halide. In any case, the different molecular compounds are in a specific stoichiometric ratio.
The co-crystallization methods, according to the invention, comprise different solutions. The choice of the method is due to the physical state (solid or liquid) of the IPBC and/or the co-crystallisation agent at the temperature at which the formation of the co-crystal is carried out.
Independently to the method used, the obtained co-crystals have different physical and chemical properties compared to the original compound, without altering the biological activity of the active pharmaceutical ingredient. The co-crystals are more performing than the pure IPBC molecule even when used to prepare formulations such as solutions, emulsions, suspensions, powders, foams, pastes, granules, tablets and inhalers, or microencapsulated in polymers. The formulations, according to the invention, can be prepared by conventional methods.