Evaluation of the bioavailability of drugs intended to act within the skin following the application of complex topical products requires the application of multiple experimental tools, which must be ...quantitative, validated, and, ideally and ultimately, sufficiently minimally invasive to permit use in vivo. The objective here is to show that both infrared (IR) and Raman spectroscopies can assess the uptake of a chemical into the stratum corneum (SC) that correlates directly with its quantification by the adhesive tape-stripping method. Experiments were performed ex vivo using excised porcine skin and measured chemical disposition in the SC as functions of application time and formulation composition. The quantity of chemicals in the SC removed on each tape-strip was determined from the individually measured IR and Raman signal intensities of a specific molecular vibration at a frequency where the skin is spectroscopically silent and by a subsequent conventional extraction and chromatographic analysis. Correlations between the spectroscopic results and the chemical quantification on the tape-strips were good, and the effects of longer application times and the use of different vehicles were clearly delineated by the different measurement techniques. Based on this initial investigation, it is now possible to explore the extent to which the spectroscopic approach (and Raman in particular) may be used to interrogate chemical disposition deeper in the skin and beyond the SC.
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An important question in the development of a dermatological drug product is whether a target concentration has been achieved in, for example, the viable epidermis following topical ...administration. When attempting to address this challenge, it is essential to consider the role of excipients in the formulation that may influence drug partitioning and diffusion in the different layers of the skin. The objective, therefore, was to correlate, in human subjects, the skin pharmacokinetics of diclofenac (specifically, its uptake into and clearance from the stratum corneum (SC)) from an approved drug product (Voltaren® medicated plaster) with the in vivo co-uptake of two key excipients, namely propylene glycol and butylene glycol. SC sampling was used to assess diclofenac input into the skin during patch application, and its subsequent clearance post-removal of the delivery system. In parallel the uptake of the two glycol excipients was also measured. Drug and excipient amounts in the SC increased with time of application up to 6 h and, for diclofenac, no further increase was observed when the administration was prolonged to 12 h. When the plaster was removed after 6 h of wear, diclofenac cleared relatively slowly from the SC suggesting that drug binding with a slow off-rate had occurred. The results indicate that the optimisation of drug delivery from a topical formulation must take into account the disposition of key excipients and their impact on dermato-pharmacokinetics in general.
Organoleptic excipients used in pediatric antibiotics Nakama, K.A.; Dos Santos, R.B.; Serpa, P. ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
October 2019, 2019-Oct, 2019-10-00, 20191001, Letnik:
26, Številka:
7
Journal Article
Recenzirano
Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance.
The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for ...pediatric use marketed in Brazil.
The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form.
Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed.
Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.
Abstract Objectives To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. Methods Retrospective data from MS patients who became pregnant at any time of their ...disease were sent to a Brazilian database, using a specific file for this purpose. Results Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients’ average age at pregnancy was 29.8 years (range 16–42). EDSS at start of pregnancy was 1.5 ± 1.4; and the relapse rate in the year preceding pregnancy was 1.2 ± 1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. Conclusions Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.
Among Brazilian initiatives to scale up TB preventive therapy (TPT) are the adoption of the 3HP regimen (12 weekly doses of rifapentine and isoniazid INH) in 2021 and the implementation in 2018 of ...the TPT surveillance information system. Since then, 63% of the 76,000 eligible individuals notified completed TPT. Recommended regimens in this period were 6H, 9H (6 or 9 months of INH) and 4R (4 months of rifampicin).
To analyse the factors associated with TPT non-completion.
We analysed the cohort of TPT notifications from 2018 to 2020. Robust variance Poisson regression model was used to verify the association of TPT non-completion with sociodemographic, clinical and epidemiological variables.
Of the 39,973 TPT notified in the study period, 8,534 (21.5%) were non-completed, of which 7,858 (92.1%) were lost to follow-up. Age 15-60 years (relative risk RR 1.27, 95% confidence interval 95% CI 1.20-1.35), TPT with isoniazid (RR 1.40, 95% CI 1.19-1.64) and Black/mixed race (RR 1.17, 95% CI 1.09-1.25) were associated with a higher risk of non-completion.
Individuals in situations of social and financial vulnerability such as being Black/
race, younger and on longer TPT regimens were more likely to be associated with TPT incompletion.
Hollow cathode discharge (HCD) is widely used in material processing and plasma emission spectroscopy due to several advantages over other plasma sources. Basically, the HCD consists of a cathode ...with a hollow structure (cavity, hole, or parallel faces) and an anode of arbitrary shape. In this investigation, experimental studies on low-pressure plane-parallel HCD operated at different process conditions are reported. Herein, we investigate the dependence of the discharge current on the product of the gas pressure and inter-cathode distance (
pD
). In addition, the electron temperature and density were inferred from the current-voltage characteristics of a single cylindrical Langmuir probe positioned between the cathodes, on the discharge axis. The measurements were carried out at different gas pressures, magnetic field intensities, working gases, inter-cathode distances, cathode materials, and discharge voltages. The results showed that, at different gas pressures, the maximum discharge current (
I
d,max
) is not only a function of the product
pD
, but also of the pressure itself. Application of a uniform longitudinal magnetic field improved plasma confinement between cathodes, leading to a substantial increase in
I
d,max
in most of the situations considered in this study. However, for oxygen discharge, a strong discharge current reduction after the application of the magnetic field was observed. In relation to the Langmuir probe studies, it was observed that the uniform longitudinal magnetic field reduced the electron temperature, but this behavior depends strictly on
pD
. The typical values of electron density and electron temperature in the case of the nitrogen discharge were
n
e
= 10
17
m
−3
and
T
e
= 2.5 eV, respectively. Finally, our experiments showed that the
pD
range for hollow cathode effects was between 0.2–5 Pa m.
Hybridization is a fundamental evolutionary and ecological process with significant conservation ramifications. Sea turtle hybridization occurs at unusually high frequencies along the northeastern ...coast of Brazil. To better understand the process, we studied the reproductive output, migration patterns (through satellite telemetry), and isotopic niches of loggerhead turtles
Caretta caretta
and olive ridley turtles
Lepidochelys olivacea
and their hybrids. We classified 154 nesting females as loggerhead (n = 91), olive ridley (n = 38), or hybrid (n = 25) based on mitochondrial and nuclear DNA. Further, we compared nesting female morphological data and reproductive parameters (clutch size, emergence success, hatchling production, incubation period) of 405 nests among hybrids and parental species. We found no significant differences among the 3 groups when hatchling production was corrected for female body size, indicating that hybrids and parental species produce similar numbers of hatchlings per clutch. Satellite tracking of 8 post-nesting hybrid females revealed shared foraging grounds with both parental species, as well as neritic migrations between foraging and nesting areas similar to those previously reported for loggerheads and olive ridleys. Analyses of
13
C and
15
N isotope values (n = 69) further confirmed this pattern, as hybrid isotopic niches overlapped extensively with both parental species. Thus, given the similarities presented between hybrids and their parental species in reproductive, ecological, and behavioral characteristics, we conclude that these hybrids may persist along with other sea turtle nesting populations in the area, with research and conservation implications.
Summary
The aim of this study was to investigate the effects of a dietary Allium sativum (garlic) addition on growth, parasite infestation and blood parameters in Colossoma macropomum (tambaqui) ...using 12 net‐cages (1 m3). There were four treatments with three replicates each (15 fish per replicate). Tambaqui of 112.4 g mean weight were fed for 45 days with diets containing 0, 15, 30 and 45 g of fresh garlic kg−1 feed. Garlic did not affect the tambaqui survival, growth, feed conversion, body condition, plasma glucose levels, total plasma protein levels or red blood cells. Total leukocyte and lymphocyte numbers decreased in fish fed diets containing 45 g garlic kg−1 feed, but neutrophils decreased in fish fed diets containing 15, 30 and 45 g garlic kg−1 diet, while the number of immature leukocytes increased in fish fed 30 g and 45 g garlic kg−1diet. Gills in fish fed 30 and 45 g kg−1 diet had lower infestation (52% and 63%, respectively) of Anacanthorus spathulatus (Monogenea) compared to controls. The application of garlic in diets improved the response of leukocytes and enhanced the resistance to infections by monogeneans.
While many studies have addressed the direct effects of 1α,25(OH)
2D
3 on breast cancer (BC) cells, stromal–epithelial interactions, which are important for the tumor development, have been largely ...ignored. In addition, high concentrations of the hormone, which cannot be attained
in vivo, have been used. Our aim was to establish a more physiological breast cancer model, represented by BC tissue slices, which maintain epithelial–mesenchymal interactions, cultured with a relatively low 1α,25(OH)
2D
3 concentration, in order to evaluate the vitamin D pathway. Freshly excised human BC samples were sliced and cultured in complete culture media containing vehicle, 0.5
nM or 100
nM 1α,25(OH)
2D
3 for 24
h. BC slices remained viable for at least 24
h, as evaluated by preserved tissue morphology in hematoxylin and eosin (HE) stained sections and bromodeoxyuridine (BrdU) incorporation by 10% of tumor cells. VDR mRNA expression was detected in all samples and CYP24A1 mRNA expression was induced by 1α,25(OH)
2D
3 in both concentrations (but mainly with 100
nM). Our results indicate that the vitamin D signaling pathway is functional in BC slices, a model which preserves stromal–epithelial interactions and mimics
in vivo conditions.
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