| Grant number: | 18/24378-6 |
| Support type: | Regular Research Grants |
| Duration: | March 01, 2019 - May 31, 2021 |
| Field of knowledge: | Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials |
| Principal researcher: | Flávio Junior Caires |
| Grantee: | Flávio Junior Caires |
| Home Institution: | Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil |
| Assoc. researchers: | Daniel Rinaldo ; Joop ter Horst |
Abstract
The low aqueous solubility and low oral bioavailability of the active pharmaceutical ingredients (APIs) are the main constraints during the development of new products. Several approaches have been used to improve the aqueous solubility of poorly soluble drugs, but the success of such approaches depends on the physical and chemical nature of the molecules being developed. The co-crystallization of drugs offers a great opportunity for the development of new solid forms of drugs with higher physicochemical properties, such as melting point, compaction capacity, solubility, stability, bioavailability and permeability, preserving the pharmacological properties of the APIs. The co-crystals are multicomponent systems, wherein two components, one the active pharmaceutical ingredient and the other a coformer are present in stoichiometric ratio and maintained through non-covalent interactions in the crystal structure.Thus, the present project aims at the synthesis, thermoanalytical studies, characterization, solubility determination and comparative dissolution of the co-crystals obtained from the drug valsartan, candesartan cilexetil and Olmesartan medoxomil, drugs that present serious problems of solubility and bioavailability. The cocrystals will be obtained by the mechanochemical method (Liquid assisted Grinding (LAG) and without solvent), with the aid of a ball mill, by the slurry method and also by crystallization in solution using solvents and / or solvent mixtures. The optimization of the synthesis method and the characterization of the cocrystals that are obtained will be performed using the following techniques: crystallisation system (Crystal 16); thermomicroscopy (hot stage coupled to a optical microscope); differential scanning calorimetry (DSC); simultaneous thermogravimetric analysis and differential scanning calorimetry (TG-DSC); Fourier transform infrared spectroscopy (FTIR); density functional theory (DFT) calculation; solid state nuclear magnetic resonance spectroscopy (NMR); powder/single crystal X-ray diffraction; Experiments will be performed to determine the solubility and the comparative dissolution tests. Thus, it is expected to obtain cocrystals that are able to provide improvements in physicochemical properties and therefore to provide an innovative approach to improve the bioavailability of these drugs. (AU)
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