Thermoanalytical characterization and dissolution profiles studies of metronidazole tablets

O objetivo desse trabalho foi caracterizar através de métodos termoanalíticos e perfil de dissolução, formulações de comprimidos de metronidazol de cinco laboratórios (R, G, SA, SB, SC) comercializadas no mercado nacional. O perfil termoanalítico das formulações permitiu visualizar em algumas delas, interações entre os componentes levando a formação de eutéticos com ponto de fusão inferior ao do metronidazol. As formulações SB e SC apresentaram perfis de dissolução que não contemplaram o preconizado na literatura, confirmando os resultados termoanalíticos. Todas formulações foram comparadas matematicamente através de modelos cinéticos de liberação, demonstrando que o principal mecanismo foi o de primeira ordem. As formulações foram comparadas estatisticamente através de análise de variância (ANOVA) e pós-teste como Tukey e Newman-Kells, apresentando diferenças significativas relacionadas à eficiência de dissolução.In the present study dissolution tests and thermoanalytical (TA) techniques were applied to metronidazole tablets from five laboratories (R, G, SA, SB, SC) available on the Brazilian market. The TA profiles indicated that in some formulations interactions between components led to eutectic products with lower melting points than metronidazole. The formulations SB and SC showed dissolution profiles that did not agree with published standards, confirming the TA results. All dissolution data were mathematically compared with kinetic models of release, demonstrating the main release mechanism was first order in all the tablets. The formulations were statistically compared by ANOVA and post-hoc tests (Tukey and Newman-Keuls), reveling significant differences in dissolution efficiency (DE).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Mechanical and imaging studies of hydrophilic matrices formed by polymeric blends of HPMC and Carbopol

El objetivo de este trabajo fue el de examinar las propiedades mecánicas y de imagen de mezclas poliméricas de hidroxipropilmetilcelulosa (HPMC) y carbopol, determinando la influencia del pH. Dos formulaciones de comprimidos fueron preparadas mezclando HPMC y carbopol en distintas concentraciones. Las proporciones de polímeros usadas fueran 7:3 y 9:1 para HPMC y carbopol, desarrollando las formulaciones F1 y F2, respectivamente. Los resultados indican que las matrices exhiben mecanismos diferentes de captación líquida, hinchamiento y erosión. Los resultados también demuestran significativa influencia del pH en estos parámetros. La formulación que contiene alto nivel de Carbopol es apropiada para la liberación de drogas hidrófilas en razón de hincharse más rápidamente, mientras que la formulación con el nivel más alto de HPMC es más adecuada para la liberación de drogas por la erosión principalmente, desde que esta matriz es más erosionable.The purpose of this work was to examine the mechanical and imaging properties of polymeric blends of hydroxypropylmethylcellulose (HPMC) and carbopol determining the pH effect of different pH values. Two formulations were prepared by mixing HPMC and Carbopol in different concentrations and later compressing in a single punch tablet machine. The ratios of polymer used were 7:3 and 9:1 for HPMC and carbopol, producing formulations F1 and F2, respectively. The results indicate that the matrices exhibit different mechanisms of liquid uptake, swelling and erosion. The results also demonstrate that pH of the medium influences significantly on these parameters. The formulation containing high level of carbopol is appropriate for release of hydrophilic drugs because of faster swelling, while the formulation with highest level of HPMC is more adequate to drug release mainly by erosion, since this matrix is more erodible.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Influence of the complexation with β-cyclodextrin on dexamethasone acetate release from hydrophilic matrices of Hydroxypropylmethylcellulose (HPMC) and Polyethylene oxide (PEO)

O acetato de dexametasona (ADM), um fármaco de escassa solubilidade, foi incorporado em sua forma livre, complexada ou misturada fisicamente com β-ciclodextrina (βCD) em matrizes hidrofílicas de hidroxipropilmetilcelulose (HPMC) ou polioxetileno (PEO) em diferentes graus de viscosidade/peso molecular. A avaliação dos perfis de liberação in vitro indicou que as formulações mostraram-se eficazes na extensão da liberação do ADM, sendo a velocidade de liberação modificada como conseqüência da complexação. A aplicação de modelos matemáticos (zero ordem, Higuchi e Korsmeyer-Peppas) permitiu a caracterização da cinética de liberação, indicando que o método de complexação, polímero e viscosidade/peso molecular influenciaram os mecanismos pelos quais o fármaco foi liberado. Além disso, a equação de Weibull mostrou-se útil na diferenciação dos perfis de liberação de algumas formulações, quando os parâ- metros escala (α) e formato (β) foram avaliadosThe dexamethasone acetate (DMA), a poorly water soluble drug, was incorporated alone, complexed or physically mixed with β-cyclodextrin (βCD), in hydrophilic matrix capsules containing hydroxypropyl methylcellulose (HPMC) or polyethylene oxide (PEO) in different viscosity/molecular weight. The evaluation of in vitro release profiles indicated that the formulations were effective in the extension of DMA release, being the release velocity modified due to complexation. The application of the mathematical models (zero order, Higuchi and Korsmeyer-Peppas) allowed the characterization of the release kinetics, indicating that the complexation method, polymer and viscosity/molecular weight influenced the mechanisms by which drug was released. Nevertheless, Weibull equation revealed to be useful in the differentiation of release profiles of some formulations, when the scale (α) and format (β) parameters were evaluatedColegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical Properties and Dissolution Studies of Dexamethasone Acetate-β-Cyclodextrin Inclusion Complexes Produced by Different Methods

Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug, and β-cyclodextrin (βCD) were obtained to improve the solubility and dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA was significantly increased in the presence of βCD (33-fold) and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation, freeze drying) and physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption and optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles of solid complexes were determined and compared with those DMA alone and their physical mixture, in three different mediums: simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4) and distilled water. The dissolution studies showed that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics. According to the results, the freeze–dried and kneaded products exhibited higher dissolution rates than the drug alone, in all the mediums

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry

BACKGROUND AND OBJECTIVES: COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS: Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis