3 research outputs found
Comparative evaluation of acetaminophen form (I) in commercialized paracetamol brands
The vibrational spectroscopy (FT-IR/Raman) and X-ray diffraction techniques are combined alongside the principal component analysis (PCA) as novel integrated analytical techniques to comparatively investigate latent chemical information and quality discrepancies regarding twelve (12) commercialized paracetamol (APAP) brands. This research aim is to present an advanced computational screening approach using spectroscopic and X-ray diffraction techniques with PCA as a tool to investigate the structural properties of pharmaceutical solid drugs by vibrational mode and diffraction pattern analyzes. Herein, the acquired vibrational, absorption, and diffraction datasets of APAP functionalities were collected at spectra and diffraction regions of intense peaks to develop predictive PCA models. Interestingly, the PCA models invalidate drug falsification in all the brands and predicted dissimilarities arising from observed differences in the vibrational/absorption modes of APAP form (I) in some brands due to excessive use of cheap (fillers and hydrocolloid alternatives) excipients. The PCA-PXRD model unveils discrepancies regarding the contrasting diffraction patterns (structure-property relationships) observed for APAP form (I) in the brands, which suggests differences in their pharmacokinetic properties cause an unapparent structural modification. Nevertheless, the comparative drug release studies present a%CDR between 93 and 98% in 30 min for all the brands, thus, structural modifications of APAP form (I) as observed in some brands show no serious effects on the%CDR and/ or solubility. Finally, it is expected that this work will contribute to the advances in screening techniques toward addressing the global drug challenges, especially in developing countries
Synthesis of new cocrystal solid form of fluconazole-fumaric acid
Pharmaceutical cocrystals are multicomponent crystalline solids comprised of
an active pharmaceutical ingredient (API) and one or more co-formers
interacting through hydrogen bonding or other weak interactions like the π-stack
and van der Waals interactions. Fluconazole (FLZ) is a triazole antifungal drug
used in the treatment and prevention of superficial and systemic fungal
infections. It is also used to prevent and treat meningitis. Cocrystallization is an
alternative approach for enhancement of drug. It can be performed using neat
grinding, solvent assisted grinding, solvent evaporation, cooling evaporation
and slurry cocrystallization. In this work, a new cocrystal Fluconazol-Fumaric
acid monohydrate was synthesized via 1:1 stoichiometric amount of FLZ and
FUM at different conditions. The characterization of the synthesized cocrystals
was achieved using Raman spectroscopy, differential scanning calorimetry,
powder X-ray diffraction and single crystal X-ray diffraction. The results
obtained for the characterization of the samples showed some obvious
differences among the spectra, diffractograms and thermograms. The single
crystal X-ray diffraction analysis of the new structure shows a cocrystal where
the fluconazole molecules are attached to the fumaric acid and water molecules
respectively through hydrogen bonds, gave unique cell dimensions for an
assumed structure C17H18F2N6O6 with a space group of P21/n, a = 17.053(3) Å,
b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°, γ= 90°, V = 1947.3(6) Å3.
This work is the first to report a monohydrate cocrystal structure of fluconazole
and fumaric acid.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Cocristais farmacêuticos são sólidos cristalinos multi-componentes compostos
de um ingrediente ativo farmacêutico (API) e um ou mais co-formadores
interagindo através de ligações de hidrogênio ou outras interações fracas como
as π-stack e Van der Waals. Fluconazol (FLZ), é um fármaco anti-fúngico
triazol utilizado no tratamento e prevenção de infecções fúngicas superficiais e
sistémicas. É também utilizado para prevenir e tratar a meningite.
Cocristalização é uma abordagem alternativa para melhorar as propriedades de
fármacos. Pode ser realizada através de moagem a seco, moagem assistida
por solvente, evaporação de solvente e cristalização em suspensão. Neste
trabalho, um novo co-cristal Fluconazol-Ácido Fumarico monohidrato foi
sintetizado utilizando uma estequimetria 1:1 em diferentes condições. A
caracterização dos co-cristais sintetizados foi realizada utilizando
espectroscopia Raman, calorimetria exploratória diferencial, difração de raios-X
em pó é por monocristal. Os resultados obtidos para a caracterização das
amostras mostrou algumas diferenças obvias entre os espectros, difratogramas
e termogramas. A difração de raios-X de monocristal mostrou uma nova
estrutura onde as moléculas de fluconazol estão ligadas ao ácido fumárico e a
uma molécula de água através de ligações de hidrogênio, originando uma
estrutura única C17H18F2N6O6 de grupo espacial P21/n e dimensões da célula
unitária a = 17.053(3) Å, b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°,
γ= 90°, V = 1947.3(6) Å3. Este trabalho é o primeiro a relatar uma estrutura de
co-cristal mono-hidrato de fluconazol e acido fumárico
Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review
Abstract Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in protein folding by assisting in the assembly of misfolded proteins. Under cellular stress conditions, GRP78 can translocate to the cell surface (csGRP78) were it interacts with different ligands to initiate various intracellular pathways. The expression of csGRP78 has been associated with tumor initiation and progression of multiple cancer types. This review provides a comprehensive analysis of the existing evidence on the roles of GRP78 in various types of cancer and other human pathology. Additionally, the review discusses the current understanding of the mechanisms underlying GRP78's involvement in tumorigenesis and cancer advancement. Furthermore, we highlight recent innovative approaches employed in downregulating GRP78 expression in cancers as a potential therapeutic target