Caracterización de nanofibras lignocelulósicas de tallos de tabaco para aplicaciones farmacéuticas

Lignocellulosic nanofibers derived from tobacco stalk can have countless applications in polymers composites, textile, cosmetics, and pharmaceuticals. Thus, it is important to evaluate biomass characteristics such as the presence of nicotine. In this study, nanofibers were obtained by mechanical fibrillation while cellulose content (0.5 and 2.0%) and drying methods were varied. Nanofibers were characterized by thin layer chromatography, 1H NMR, morphological analysis, α-cellulose content, Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis. Results demonstrate the absence of nicotine in tobacco stalk. The grinding mill process was efficient to produce by freeze - drying, nanofibers with fiber’s mean diameter of ~30 nm. Solid concentrations can influence the diameter of obtained fibers. Thermal stability increased and crystallinity decreased when alkali treatment was applied. The characterization techniques applied enable the evaluation of tobacco stalk and expanded its application to pharmaceutics.Nanofibras lignocelulósicas derivadas do caule do tabaco podem ter inúmeras aplicações em compósitos poliméricos, tecidos, cosméticos e produtos farmacêuticos. Assim, é importante avaliar características da biomassa como a presença de nicotina. Neste estudo, as nanofibras foram obtidas por fibrilação mecânica, enquanto o teor de celulose (0,5 e 2,0%) e os métodos de secagem foram variados. As nanofibras foram caracterizadas por cromatografia em camada delgada, 1H RMN, análise morfológica, conteúdo de α-celulose, espectroscopia de infravermelho com transformada de Fourier, difração de raios-X e análises térmicas. Os resultados demonstram a ausência de nicotina no caule do tabaco. O processo de moagem foi eficiente para produzir por liofilização, nanofibras com diâmetro médio da fibra de ~ 30 nm. As concentrações de sólidos podem influenciar o diâmetro das fibras obtidas. A estabilidade térmica aumentou e a cristalinidade diminuiu quando o tratamento alcalino foi aplicado. As técnicas de caracterização aplicadas possibilitaram a avaliação do caule do tabaco e ampliaram sua aplicação na área farmacêutica.Las nanofibras lignocelulósicas derivadas del tallo del tabaco pueden tener innumerables aplicaciones en compuestos de polímeros, textiles, cosméticos y productos farmacéuticos. Por tanto, es importante evaluar las características de la biomasa como la presencia de nicotina. En este estudio, las nanofibras se obtuvieron mediante fibrilación mecánica mientras se variaba el contenido de celulosa (0,5 y 2,0%) y los métodos de secado. Las nanofibras se caracterizaron por cromatografía en camada delgada, 1H RMN, análisis morfológico, contenido de α-celulosa, espectroscopia infrarroja por transformada de Fourier, difracción de rayos X y análisis térmicas. Los resultados demuestran la ausencia de nicotina en el tallo del tabaco. El proceso del molino fue eficiente para producir mediante liofilización, nanofibras con un diámetro medio de fibra de ~ 30 nm. Las concentraciones de sólidos pueden influir en el diámetro de las fibras obtenidas. La estabilidad térmica aumentó y la cristalinidad disminuyó cuando se aplicó un tratamiento con álcali. Las técnicas de caracterización aplicadas permiten evaluar el tallo del tabaco y ampliar su aplicación a la industria farmacéutica

Compatibility study of rosmarinic acid with excipients used in pharmaceutical solid dosage forms using thermal and non-thermal techniques

Rosmarinic acid (RA) is a phenolic compound that presents well-documented anti-inflammatory, antioxidant and antitumor activities, and based on its pharmacological potential and poor bioavailability, several solid dosage forms have been developed to RA delivery. Therefore, in literature, there are no reports about RA compatibility with excipients. In this regard, the aim of the present study was to evaluate, for the first time, the compatibility of RA with excipients commonly used in solid dosage forms at a 1:1 (RA: excipient) ratio using differential scanning calorimetry (DSC), thermogravimetry (TG), Fourier-transform infrared (FTIR), solid-state nuclear magnetic resonance (ssNMR), and isothermal stress testing (IST) coupled with liquid chromatography (LC). The excipients selected were hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), lactose monohydrate (LAC), polyvinylpyrrolidone (PVP), talc (TALC), croscarmellose sodium (CCS), and magnesium stearate (MgSTE). According to DSC results, physical interactions were found between RA and HPMC, LAC, CCS, and MgSTE. The TG analyses confirmed the physical interactions and suggested chemical incompatibility. FTIR revealed physical interaction of RA with TALC and MgSTE and the ssNMR confirmed the physical interaction showed by FTIR and excluded the presence of chemical incompatibility. By IST, the greatest loss of RA content was found to CCS and MgSTE (>15%), demonstrating chemical incompatibilities with RA. High temperatures used in DSC and TG analyses could be responsible for incompatibilities in binary mixtures (BMs) with HPMC and LAC, while temperature above 25 C and presence of water were factors that promote incompatibilities in BMs with CCS and MgSTE. Overall results demonstrate that RA was compatible with MCC and PVP

Toward a greener multifunctional pharmaceutical excipient: <i>in vivo</i> safety evaluation of nanofibrillated cellulose from tobacco stalk

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175–5,000 mg·kg−1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p −1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.</p

Compatibility study of rosmarinic acid with excipients used in pharmaceutical solid dosage forms using thermal and non-thermal techniques

Rosmarinic acid (RA) is a phenolic compound that presents well-documented anti-inflammatory, antioxidant and antitumor activities, and based on its pharmacological potential and poor bioavailability, several solid dosage forms have been developed to RA delivery. Therefore, in literature, there are no reports about RA compatibility with excipients. In this regard, the aim of the present study was to evaluate, for the first time, the compatibility of RA with excipients commonly used in solid dosage forms at a 1:1 (RA: excipient) ratio using differential scanning calorimetry (DSC), thermogravimetry (TG), Fourier-transform infrared (FTIR), solid-state nuclear magnetic resonance (ssNMR), and isothermal stress testing (IST) coupled with liquid chromatography (LC). The excipients selected were hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), lactose monohydrate (LAC), polyvinylpyrrolidone (PVP), talc (TALC), croscarmellose sodium (CCS), and magnesium stearate (MgSTE). According to DSC results, physical interactions were found between RA and HPMC, LAC, CCS, and MgSTE. The TG analyses confirmed the physical interactions and suggested chemical incompatibility. FTIR revealed physical interaction of RA with TALC and MgSTE and the ssNMR confirmed the physical interaction showed by FTIR and excluded the presence of chemical incompatibility. By IST, the greatest loss of RA content was found to CCS and MgSTE (>15%), demonstrating chemical incompatibilities with RA. High temperatures used in DSC and TG analyses could be responsible for incompatibilities in binary mixtures (BMs) with HPMC and LAC, while temperature above 25 C and presence of water were factors that promote incompatibilities in BMs with CCS and MgSTE. Overall results demonstrate that RA was compatible with MCC and PVP

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study

To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use