Obtenção, caracterização e avaliação físico-química de cocristais de ácido cinâmico
One of the limiting steps for the Active Pharmaceutical Ingredient (API) to be absorved by oral ways and to act pharmacologically, is its previous solubilization in the aqueous means. Many candidates for IFAs have low aqueous solubility, and to alternatively offer physical or chemical modificatio...
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| Formato: | Dissertação |
| Idioma: | pt_BR |
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/27431 |
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| Resumo: | One of the limiting steps for the Active Pharmaceutical Ingredient (API) to be absorved
by oral ways and to act pharmacologically, is its previous solubilization in the aqueous
means. Many candidates for IFAs have low aqueous solubility, and to alternatively offer
physical or chemical modifications in these substances, are very necessary. Cinnamic
acid (AC) is an IFA candidate that has studies demonstrating several important
pharmacological activities, such as antimicrobial and antitumor, with low toxicity. The
use of cocrystallization is one of the main strategies applied to improve the aqueous
solubility of the IFA. The aim was to obtain the cocrystals of CA and its characterization
and physical-chemical evaluation. Physical mixtures (MFs) were prepared manually by
mixing the powders, and the cocrystals (CCs) were obtained by solvent evaporation in
stoichiometric amounts of IFA and copolymer in molar ratio 1: 1. The characterization
was performed using techniques such as X-ray Diffraction (XRD), Differential Scanning
Calorimetry (DSC), Infrared Spectroscopy with Fourier Transform (FTIR) and Scanning
Electron Microscopy (SEM). For the physical and chemical evaluation of the possible
CCs, an analytical method was developed and optimized by Ultra High Pressure Liquid
Chromatography (UHPLC) and validated according to the current resolution. The
physicochemical evaluation of the cocristais was performed by water saturation
solubility test, and the solubility determination was expressed by concentration
measurements. The results of characterization by XRD evaluation of the powder
showed that the interaction of the AC with 8 coformers did not show changes in the
diffraction pattern of the solid samples obtained after rotary evaporation. However, the
interaction of CA with other 3 coformers, CAF, NIC and TIA in the obtained samples of
CCs, showed changes by powder XRD in the diffraction pattern characterized by the
appearance of new unidentified peaks in the diffraction pattern of the isolated
pharmaceutical ingredients. From the DSC curves, it was noticed that the fusion of the
CCs samples occurred at lower temperatures compared to the isolated pharmaceutical
ingredients. The FTIR spectra showed shifts of the main vibrations to lower
frequencies, related to the possible hydrogen connections created. SEM
photomicrographs showed a brief change in the crystalline habit of CCs. The analytical
method by UHPLC was developed in a gradient mode with mobile phase 0.1%
trifluoroacetic acid (TFA) in ultrapure water and methanol under optimized
chromatographic conditions. The method was selective, linear, precise, accurate and
robust. After solubility test, the saturation solubility in aqueous medium for the isolated
CA was 0.55 mg.mL-1, and in the CCs with CAF, NIC and TIA were 0.9, 0.86 and 0.64
mg.mL-1, being it considereted a significant increase of 63%, 56% and 16%,
respectively, in the aqueous solubility of the IFA. Findings proved the importance of
the use of solid state characterization techniques in the identification of cocrystals,
however, it is still necessary to introduce others confirmatory techniques, such as
single crystal XRD. The increase in the aqueous solubility of CA correlates directly with
the modifications provided by the cocrystals, which may favor the production of a
technologically more favorable pharmaceutical product. |
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