Banca de DEFESA: JONH ANDERSON BORGES DOS SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : JONH ANDERSON BORGES DOS SANTOS
DATA : 28/03/2019
HORA: 09:00
LOCAL: SALA 2 DO PPGCF
TÍTULO:

Preparation, physico-chemical characterization and solubility evaluation of pharmaceutical cocrystals of cinnamic acid

PALAVRAS-CHAVES:

Cinnamic acid. Coformer. Cocrystals. Physical-chemical characterization. Solubility.

PÁGINAS: 197
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

One of the limiting steps for the Active Pharmaceutical Ingredient (API) to be absorbed oral and to act pharmacologically is its previous solubilization in the aqueous media. Many candidates for IFAs have low aqueous solubility, and alternatively propose physical or chemical modifications in these substances, are 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 objective was to obtain the cocrystals of CA and to carry out its characterization and physical-chemical evaluation. Physical mixtures (MFs) were prepared manually by mixing the powders and the cocrystals (CCs) were obtained by evaporation of solvent with 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 physical-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 rotaevaporation. However, the interaction of CA with other 3 coformers, CAF, NIC and TIA in the samples of CCs obtained showed by powder XRD changes 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 observed 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 bonds formed. SEM photomicrographs showed a brief change in the crystalline habit of CCs. The analytical method by UHPLC was developed by 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, thus considering a significant increase of 63%, 56% and 16%, respectively, in the aqueous solubility of the IFA. Results demonstrated the importance of the use of solid state characterization techniques in the identification of cocrystals, however, it is still necessary to introduce more confirmatory techniques, such a 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.

MEMBROS DA BANCA:
Interno - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Presidente - 1492900 - CICERO FLAVIO SOARES ARAGAO
Externo à Instituição - FÁBIO SANTOS DE SOUZA - UFPB
Externo à Instituição - JOSEAN FECHINE TAVARES - UFPB