A comparative in vitro assay of drug release performance of pyridostigmine bromide tablets

Myasthenia gravis is an autoimmune disease that destroys key components of the neuromuscular system. The most common therapy uses reversible inhibitors of cholinesterase activity, such as pyridostigmine bromide (PB). The nature of this illness implies that we must be sure that all available PB immediate-release tablets produce the same therapeutic response. The aim of this study was to analyze PB immediate-release formulations provided by pharmacies in MERCOSUR countries A, B, and C. The formulations, which were produced in different manufacturing plants of the same multinational company, were analyzed following USP 29 specifications. The products fulfilled the assay, uniformity of dosage units, and dissolution test in S2 stage. Dissolution profiles were carried out following EMEA and FDA regulations, and the similarity factor (f2) was applied to A and C but not B, as this one did not fulfill the dissolution requirements. Pyridostigmine bromide tablets from countries A and C are considered to be similar and could be interchangeable. Formulation B exhibited such different dissolution behavior that its interchangeability is discouraged, as well as its introduction in countries A and C from the manufacturing country B.Fil: Pizzorno, Maria Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Zubata, Patricia D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Ercolano, Irma. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Pizzorno, Maria Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Dissolution Stability study of Cefadroxil extemporaneous suspensions

Dissolution studies have become matter of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The dissolution behavior of four different brands of cefadroxil extemporaneous suspensions available in the Argentinian market was evaluated. The deliverable volume, pH, visual appearance, uniformity of dosage units, and assay were also studied. Powders for oral suspension were stored under different aging conditions. Samples at room temperature and refrigerated conditions were taken at several time points to carry out the dissolution stability study during the expiration period of the reconstituted form. Marked differences were recorded with respect to in vitro dissolution behavior between the different products under evaluation.Fil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; ArgentinaFil: Zubata, P. D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Simionato, Laura Daniela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Pizzorno, Maria Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; Argentin

Similitud e Intercambiabilidad de Formulaciones de Cefalexina

Se ha realizado un estudio de similitud de comprimidos de cefalexina 500 mg sobre cuatro marcas comerciales argentinas, con respecto a una formulación de referencia. El análisis se basó en la evaluación de los perfiles de disolución de dichas especialidades, según los requerimientos de FDA y EMEA, aceptados por ANMAT. Los resultados obtenidos permiten evaluar la similitud entre los productos y facilita la intercambiabilidad de los mismos en el acto de dispensación.Fil: González Vidal, Noelia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad Nacional del Sur; ArgentinaFil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Zubata, Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Pizzorno, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad Nacional del Sur; Argentin

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Validation of Liquid Chromatographic Method for Analysis of Tacrolimus in a Pharmaceutical Dosage Form

An accurate, simple and reproducible liquid chromatographic method was developed and validated for the determination of  tacrolimus in capsules. The analysis were performed at room temperature on a reverse phase C18 column with UV detection at 210 nm. The mobile phase consisted of  methanol-water (90 + 10) at a constant flow rate of 0.8 mL/min. The method was validated in terms of linearity, precision, accuracy and specificity by forced decomposition of tacrolimus using acid, base, water, hydrogen peroxide, heat and light. The response was linear in the range of 0.09-0.24  mg/mL (r2 = 0.9997). The relative standard deviation values for intra- and interday precision studies were 1.28 and 2.91.  Recoveries ranged between 98.06 and 102.52 %.Fil: Moyano, Maria Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Pizzorno, Maria Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Segall, Adriana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy

Background In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection.Methods This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose.Findings 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p &lt; 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p &lt; 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave.Interpretation The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/