Statins are the most commonly used group of drugs for lowering cholesterol. They belong to class II of the biopharmaceutical classification system (BCS), which means that they are poorly soluble, but permeate biological membranes well. Even if, in the literature there are reported also crystalline forms (polymorphs and salts) of statins, the pharmaceutical companies, prefer the amorphous salts forms for the formulation of the drug. The reason is that the solubility of the reported new crystalline forms is generally still less than that of the amorphous salt form. Amorphous forms are known to have low stability; witch creates problems at the formulation stage: they mix less and have worse rheological properties than crystalline systems.
In this context the main objective of the proposal is to obtain crystalline forms – co-crystals. Co-crystal formation with a suitable co-former offers the potential of improved solubility via modification of the underlying crystal structure.
For the two selected statins – Pravastatin and Pitavastatin – will be applied advanced crystal engineering and characterization techniques. For obtaining pharmaceutical co-crystals high-throughput crystallization methods will be used, whereas to increase accuracy / reliability in crystal structure determination a recently new methodology that combine X-ray diffraction with complementary techniques like Solid State NMR and molecular modeling, NMR crystallography, will be employed.
Taking into account the fact that the patent of Pravastatin sodium (market as Pravachol) has expired in 2016, and the patent of Pitavastatin calcium (markt as Livalo) will expire in 2021, new crystalline solid forms of the tow statins will give the possibility to the pharmaceutical companies to release a generic drug with improved pharmaceutical properties. The complete characterization of the new crystalline forms will be described in papers published in prestigious ISI journals.