Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan.

The work presented here aims to develop a bioadhesive monolayer film containing sumatriptan as adjuvant for the treatment of headache pain in a severe migraine attack. Permeation experiments were performed from the films prepared and from the respective solution, to evaluate the relevant permeation parameters. The effect of the penetration enhancers Transcutol, 2-pyrrolidone, and polyethylene glycol 600 was evaluated. The results obtained show that Transcutol and 2-pyrrolidone decreased sumatriptan permeation from solution, whereas a modest increase was produced by polyethylene glycol 600. The enhancers produced the same effects when they were included in the film. Compared to solution, the film showed a higher sumatriptan flux in the early times of the experiment. When the film was applied in occlusive conditions the profiles were much higher, indicating the importance of patch drying. Concerning skin retention, the bioadhesive film produced a reduction of the amount of sumatriptan remaining in the skin, but this can be advantageous in the control of drug input, since it reduces the reservoir effect in the skin and allows for an immediate interruption of drug input when the patch is removed

Coordinación de Asignaturas Obligatorias del primer curso en el Máster en Ingeniería Química

Tras el análisis de los resultados de los primeros dos cursos del Máster de Ingeniería Química (cursos académicos 2014/15 y 2015/16) impartidos en la Universidad de Alicante, ha quedado patente la necesidad de seguir coordinando las asignaturas obligatorias de este Máster. Esta coordinación que es importante para cualquier curso universitario, es aún más necesaria en másteres como éste que empiezan su docencia en el mes de octubre, en vez de en septiembre como lo hacen muchos grados. El trabajo que proponemos tiene un carácter empírico y lleva asociado un doble propósito: por una parte se trata de corroborar si la coordinación realizada por los profesores meses antes del comienzo curso 2016/17 se ha llevado a cabo y, por otra parte, enmendar la coordinación para ser aún más realistas de cara al curso 2017/18. La intención final de la coordinación es lograr que el alumno lleve una carga semanal homogéneamente distribuida durante el cuatrimestre, ajuste su trabajo no presencial a las horas que conllevan los créditos ECTS de la asignatura, y solucionar las posibles inconsistencias que existan en las guías docentes de las asignaturas

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport

[EN] Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present. study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TI'S) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the ITS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery expefiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89 +/- 0.81 mu g cm(-2) h(-1) whereas the highest iontophoretic transport was 46.4 +/- 3.6 mu g cm(-2) h(-1). These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.The authors wish to thank the "Generalitat Valenciana" (AP-114/09; AP-155/10; AP-175/11) and the "Universidad CEU Cardenal Herrera" for their financial support. The authors also thank Pharsight corp. for the academic license of WinNonlin 5.0.1.Del Rio-Sancho, S.; Serna-Jiménez, C.; Sebastián-Morelló, M.; Calatayud-Pascual, M.; Balaguer-Fernández, C.; Femenia-Font, A.; Kalia, Y.... (2017). Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport. International Journal of Pharmaceutics. 517(1-2):104-111. https://doi.org/10.1016/j.ijpharm.2016.11.038S1041115171-

Enhanced chlorhexidine skin penetration with eucalyptus oil

Background Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic. Method Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (μg/mg of skin) was determined to a skin depth of 1500 μm by high performance liquid chromatography (HPLC). Results The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. Conclusion The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis

Physical Characterization of a New Skin Bioadhesive Film

Physical properties (roughness, gloss, mechanical, surface topography and adhesive) of a bioadhesive film for the transdermal delivery of drugs and its interactions with a skin model surface were studied. Roughness is a measurement of the small-scale variations in the height of a physical surface. No significant differences in Ra between the “x” and “y” dimensions for both the skin model and patch were detected, due to uniformity in their production. Scanning electron microscope pictures showed small particles projected from the film. Those particles resulted in increasing roughness and surface area. For the patch, gloss values measured at 20° were 6.0 ± 0.9 and at 60°, 32.2 ± 2.2 gloss units, respectively, indicating a semi-gloss material. Concerning the mechanical properties, the tensile strength of the film resulted four- to sevenfold greater than the peel force from the model skin used, indicating the suitability of the film for skin application. The adhesion to skin model depended on the amount of water used for film application and on the elapsed time between film application and removal. Finally, the model skin that was invented by Charkoudian can be used as an alternative to costly and highly variable human skin substrates since it possesses human topography

Studies on Transdermal Delivery Enhancement of Zidovudine

The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm2 area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm2 direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm2 current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm2 current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine