28 research outputs found
Attainment and characterization of ternary complexes of simvastatin-cyclodextrin-hydrossoluble polymers
The purpose of this study was to attain and characterize ternary complexes of simvastatin, β-cyclodextrin (βCD) and different polymers, and then select those that lead to a greater increase in drug solubility. The complexes were prepared with the co-evaporation method and the polymers used were polyethylene glycol 1500, polyethylene glycol 4000, povidone, copovidone, crospovidone, maltodextrin and hydroxypropyl methyl cellulose. The characterization of complexes was carried out through aqueous solubility, DSC and TG. There was an increase in solubility for all the complexes prepared with βCD and the different polymers, but only when crospovidone and maltodextrin were used was there a significant difference observed between the solubility of the physical mixture and that of the complex. The DSC curves indicate that the non-complexed drug is even in the sample of the complex with higher solubility, thus none of the polymers was able to achieve a total complexation of the drug.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Development and characterization of L-alanyl-L-glutamine containing pellets employing extrusion-spheronization method and drying process in fluidized bad equipment
No presente trabalho foram desenvolvidas e avaliadas cinco formulações de péletes, contendo
L-alanil-L-glutamina (glutamina dipeptídeo), em diferentes concentrações: F1 (9,07%); F2 (17,70%); F3
(27,98%); F4 (37,74%) e F5 (47,53%). Os péletes foram preparados pelo método da extrusão-esferonização,
seguido de secagem em equipamento de leito fluidizado. Os lotes obtidos foram submetidos aos ensaios
de: granulometria, friabilidade, densidade verdadeira e análise morfológica. Dentre as cinco formulações
avaliadas, os péletes resultantes de F3 apresentaram maior rendimento (75,80%), distribuição granulométrica
mais uniforme (89,67% dos péletes com tamanho entre 0,80 e 1,18), densidade mais elevada
(2,1634 g/mL) e melhor aspecto (1,0795 ± 0,0410). Devido às características obtidas a partir da F3 os péletes
foram considerados adequados para posterior aplicação de revestimento polimérico,visando produzir
sistema multiparticulado de liberação prolongada da substância ativa L-alanil-L-glutamina.In this work, five formulations of
L-alanyl-L-glutamine (glutamine dipeptide) containing pellets with different drug concentration were developed
and evaluated: F1 (9.07%); F2 (17.70%); F3 (27.98%); F4 (37.74%) e F5 (47.53%). Pellets were prepared by extrusion-
spheronization method and, further, dried in fluidized bad equipment. The following assays were carried
out with the batches obtained: granulometry, friability, true density and morphologic analysis. Between the five
formulations evaluated, pellets obtained from F3 present best yield (75.80%), most uniform particle size distribution
(89.67% of pellets with size in the range of 0.80 to 1.18), most high true density (2.1634 g/ml) and best aspect
(1.0795 ± 0.0410). Due to these features, pellets obtained from F3 were considered adequate to further polymeric
coating process in order to produce a multiparticulate system to prolong L-alanyl-L-glutamine release.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Development and characterization of L-alanyl-L-glutamine containing pellets employing extrusion-spheronization method and drying process in fluidized bad equipment
No presente trabalho foram desenvolvidas e avaliadas cinco formulações de péletes, contendo
L-alanil-L-glutamina (glutamina dipeptídeo), em diferentes concentrações: F1 (9,07%); F2 (17,70%); F3
(27,98%); F4 (37,74%) e F5 (47,53%). Os péletes foram preparados pelo método da extrusão-esferonização,
seguido de secagem em equipamento de leito fluidizado. Os lotes obtidos foram submetidos aos ensaios
de: granulometria, friabilidade, densidade verdadeira e análise morfológica. Dentre as cinco formulações
avaliadas, os péletes resultantes de F3 apresentaram maior rendimento (75,80%), distribuição granulométrica
mais uniforme (89,67% dos péletes com tamanho entre 0,80 e 1,18), densidade mais elevada
(2,1634 g/mL) e melhor aspecto (1,0795 ± 0,0410). Devido às características obtidas a partir da F3 os péletes
foram considerados adequados para posterior aplicação de revestimento polimérico,visando produzir
sistema multiparticulado de liberação prolongada da substância ativa L-alanil-L-glutamina.In this work, five formulations of
L-alanyl-L-glutamine (glutamine dipeptide) containing pellets with different drug concentration were developed
and evaluated: F1 (9.07%); F2 (17.70%); F3 (27.98%); F4 (37.74%) e F5 (47.53%). Pellets were prepared by extrusion-
spheronization method and, further, dried in fluidized bad equipment. The following assays were carried
out with the batches obtained: granulometry, friability, true density and morphologic analysis. Between the five
formulations evaluated, pellets obtained from F3 present best yield (75.80%), most uniform particle size distribution
(89.67% of pellets with size in the range of 0.80 to 1.18), most high true density (2.1634 g/ml) and best aspect
(1.0795 ± 0.0410). Due to these features, pellets obtained from F3 were considered adequate to further polymeric
coating process in order to produce a multiparticulate system to prolong L-alanyl-L-glutamine release.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Ocular lesions in HTLV-1 infected patients from Salvador, State of Bahia: the city with the highest prevalence of this infection in Brazil
Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs
O Gabinete Biométrico da Escola de Educação Física do Exército: medir e classificar para produzir corpos ideais, 1930-1940*
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Intrinsic Dissolution as a Tool for Evaluating Drug Solubility in Accordance with the Biopharmaceutics Classification System
The Biopharmaceutics Classification System (BCS) is a tool that was created to categorize drugs into different groups according to their solubility and permeability characteristics. Through a combination of these factors and physiological parameters, it is possible to understand the absorption behavior of a drug in the gastrointestinal tract, thus contributing to cost and time reductions in drug development, as well as reducing exposure of human subjects during in vivo trials. Solubility is attained by determining the equilibrium under conditions of physiological pH, while different methods may be employed for evaluating permeability. On the other hand, the intrinsic dissolution rate (IDR), which is defined as the rate of dissolution of a pure substance under constant temperature, pH, and surface area conditions, among others, may present greater correlation to the in vivo dissolution dynamic than the solubility test. The purpose of this work is to discuss the intrinsic dissolution test as a tool for determining the solubility of drugs within the scope of the Biopharmaceutics Classification System (BCS)
Analysis of phase transition and dehydration processes of nevirapine
Solid-state characterization of crystalline drugs is an important pre-formulation step for the development and design of solid dosage forms, such as pellets and tablets. In this study, phase transition and dehydration processes of nevirapine have been studied by differential scanning calorimetry and thermogravimetry differential thermal analysis to overcome the problems of drug formulation, namely poor solubility and poor content uniformity. Phase solubility studies elucidated the mechanism of enhanced nevirapine solubility.10815357COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR – CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO – FAPESPsem informaçã