Transdermal iontophoretic delivery of timolol maleate

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. The objective of the present study was to investigate the effect of biological variable such as guinea pig and human cadaver skin and other variables like drug concentration, current density on the transdermal iontophoretic transport of timolol maleate. The permeation profile of drug using solution and gel formulation was studied and compared. For better bioavailability, better patient compliance, and enhanced delivery, an iontophoretic drug delivery system of a timolol maleate matrix gel was formulated using Carbopol 974P. The study was conducted using silver-silver chloride electrodes across the guinea pig and human cadaver skin. Viscosity measurements and flux calculations indicated the suitability of the Carbopol 974P gel for transdermal iontophoretic delivery of timolol maleate. Anodal iontophoresis with silver-silver chloride electrode significantly increased the timolol maleate skin permeation as compared with the passive permeation study. The amount of timolol maleate transported during iontophoresis was significantly different among the different skins. However, iontophoretic gel formulations provided required flux of drug through human cadaver skin.A iontoforese transdérmica seria um método promissor para a liberação sistêmica de fármacos solúveis em água e iônicos de relativamente elevado tamanho molecular, incluindo peptídeos. O objetivo do presente estudo foi investigar o efeito da variável biológica, tais como cobaia e pele de cadáver humano, e outras variáveis como concentração do fármaco, densidade de corrente sobre o transporte transdérmico iontoforético de maleato de timolol. Comparou-se o perfil de permeação do fármaco usando a formulação de solução e de gel. Para melhor biodisponibilidade, melhor adesão do paciente e liberação aprimorada, formulou-se sistema de liberação iontoforética gel de maleato de timolol usando Carbopol 974P. O estudo foi conduzido usando eletrodos de prata-cloreto de prata na cobaia e na pele de cadáver humano. Medidas de viscosidade e de fluxo indicaram a adequação do gel Carbopol 974 P para liberação iontoforética transdérmica do maleato de timolol. A iontoforese anódica com eletrodo de prata-cloreto de prata aumentou significativamente a permeação dérmica do maleato de timolol, comparativamente à permeação passiva. A quantidade de maleato de timolol transportado durante a iontoforese foi significativamente diferente entre as diferentes peles . No entanto, as formulações iontoforéticas de gel forneceram o fluxo necessário do fármaco através da pele de cadáver humano

Changing techniques in cataract surgery: how have patients benefited?

Cataract surgery is one of the most frequently performed operations in the world. Recent advances in techniques and instrumentation have resulted in earlier intervention, improved surgical outcomes, and reduced dependence on spectacles

Development and In vitro Evaluation of Betahistine Adhesive-Type Transdermal Delivery System

Purpose: To develop a transdermal betahistine (BTH) delivery system using different pressure sensitive adhesives (PSAs) including acrylics, polyisobutylene and styrenic rubber solution.Methods: Formulations were prepared by solvent casting and adhesive transfer method. PSAs - acrylate vinylacetate (AVA), hydrophilic acrylate (HA), acrylic non-curing (ANC), polyisobutylene (PIB), and tackified styrenic rubber solution (TSR) - were evaluated for their suitability in terms of miscibility, maximum drug loading, effect on tack property and in vitro permeation through excised guinea pig skin. Furthermore, one of the PSAs was tested in relation to effect of penetration enhancers on tack property, in vitro permeation, in vivo patch adhesion performance and stability.Results: Only formulations prepared with AVA and HA were stable. Increased drug loading in these PSAs significantly reduced tack. In vitro permeation data across guinea pig skin demonstrated that BTH flux from from the formulation containing HA (F1) was significantly (p < 0.001) higher than that containing AVA (F2). Formulations containing 2 % enhancer showed good tack. Specifically, the formulation containing 2 % oleic acid as enhancer not only showed the highest permeation but also good tack property, non-irritancy for up to 36 h and stability under accelerated conditions.Conclusion: The formulation containing HA as the PSA and 2 % oleic acid as enhancer demonstrated a good potential for further development to an adhesive-type transdermal delivery system for BTH.Keywords: Meniere’s syndrome, Transdermal delivery, Betahistine, Pressure-sensitive adhesives, Penetration enhancersTropical Journal of Pharmaceutical Research December 2010; 9 (6): 516-52

Measurement of the Dependence of the Hadron Production Fraction Ratios fs/fuf_s / f_u and fd/fuf_d / f_u on BB Meson Kinematic Variables in Proton-Proton Collisions at s=13TeV\sqrt{s} = 13 TeV

The dependence of the ratio between the $B^0_s$ and $B^+$ hadron production fractions, $f_s/f_u$, on the transverse momentum $(p_T)$ and rapidity of the $B$ mesons is studied using the decay channels $B^0_s→J/ψϕ$ and $B^+→J/ψK^+$. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of $61.6  fb^{−1}$. The $f_s/f_u$ ratio is observed to depend on the $B$ $p_T$ and to be consistent with becoming asymptotically constant at large $p_T$. No rapidity dependence is observed. The ratio of the $B^0$ to $B^+$ meson production fractions, $f_d/f_u$, is also measured, for the first time in proton-proton collisions, using the $B^0→J/ψK^{*0}$ decay channel. The result is found to be within 1 standard deviation of unity and independent of $pT$ and rapidity, as expected from isospin invariance

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Performance of the local reconstruction algorithms for the CMS hadron calorimeter with Run 2 data

A description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015–2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level