34 research outputs found
Passive and iontophoretic transdermal delivery of phenobarbital: implications in paediatric therapy
Effects of iontophoresis, hydration, and permeation enhancers on human nail plate: Infrared and impedance spectroscopy assessment
Transdermal flux predictions for selected selective oestrogen receptor modulators (SERMs):Comparison with experimental results
The aim of this work was to evaluate the feasibility of delivering transdermally a series of highly lipophilic compounds (log P similar to 4-7), comprising several selective oestrogen receptor modulators and a modified testosterone (danazol). The maximum fluxes of the drugs were predicted theoretically using the modified Potts & Guy algorithm (to determine the permeability coefficient (k(p)) from water) and the calculated aqueous solubilities. The correction provided by Cleek & Bunge took into account the contribution of the viable epidermal barrier to the skin permeation of highly lipophilic compounds. Experimental measurements of drug fluxes from saturated hydroalcoholic solutions were determined in vitro through excised pig skin. Overall, the predicted fluxes were in good general agreement (within a factor of 10) with the experimental results. Most of the experimental fluxes were greater than those predicted theoretically suggesting that the 70:30 v/v ethanol-water vehicle employed may have had a modest skin penetration enhancement effect. This investigation shows that the transdermal fluxes of highly lipophilic compounds can be reasonably predicted from first principles provided that the viable epidermis, underlying the stratum corneum, is included as a potentially important contributor to the skin's overall barrier function. Furthermore, the absolute values of the measured fluxes, when considered in parallel with previous clinical studies, indicate that it might be feasible to topically deliver a therapeutically useful amount of some of the compounds considered to treat cancerous breast tissue. (C) 2013 Elsevier B.V. All rights reserved
Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for follicular drug targeting?
Drug delivery into microneedle-porated nails from nanoparticle reservoirs
Copyright © 2015. Published by Elsevier B.V.Author's post-print version. The definitive version is available from the publisher via doi: 10.1016/j.jconrel.2015.10.026This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail. The results provide clear evidence that the nanoparticles function as immobile reservoirs, sequestered on the nail surface and in the microneedle-generated pores, from which the active payload can be released and diffuse laterally into the nail over an extended period of time
Cardiovascular Paediatric Medicines Development: Have Paediatric Investigation Plans Lost Heart?
This work aimed to establish whether paediatric needs in cardiovascular diseases have been met by paediatric investigation plans (PIPs) produced since the development of the European Union Paediatric Regulation in 2007. The European Medicines Agency repository was searched for patterns in the development of paediatric medicines in general. Next, positive PIPs related to cardiovascular diseases were scrutinized for outcomes and compared to specific paediatric cardiovascular needs. In total, 1866 PIPs were identified with 12% corresponding to decisions taken for cardiovascular medicines. However, despite this therapeutic area having the greatest number of overall PIPs, only 14% of established needs in paediatric cardiovascular diseases were addressed by PIPs with positive decisions. Further, 71.9% of PIPs with decisions in cardiovascular disease corresponded to full waivers, so the product would not be studied in paediatrics. Despite the progress found in overall numbers of PIPs published, cardiovascular products are still commonly used off-label in paediatrics. Particularly, there is a need to develop products to treat heart failure and hypertension, two areas with clear unmet clinical needs in paediatrics. A case study on valsartan showed that industry, regulators, health technology assessment bodies, and prescribers should work together to reduce off-label use of paediatric cardiovascular diseases (CVD)
Prediction of iontophoretic transport across the skin
The objective of this work was to demonstrate that the efficiency of iontophoretic transport across the skin (which is measured in terms of an ion's transport number), either for drug delivery or for therapeutic drug monitoring, depends implicitly on the molar fraction of the species of interest over a wide range of experimental conditions both in vitro and in vivo. Three sets of data from the literature were assessed to establish the direct relationship between transport number and mole fraction. Linear regression between these parameters yielded slopes which correlated with the charge-carrying efficiency of the ion considered. The latter, furthermore, was proportional to the corresponding aqueous mobility and to the transport number of the ion when it is the sole species available for migration from its electrode solution (the so-called "single-carrier" situation). Finally, the principles illustrated here were equally applicable to in vitro experiments and to in vivo data obtained in a clinically relevant study (specifically, the reverse iontophoretic monitoring of lithiemia in bipolar patients). Not only does this validate an in vitro model typically used in iontophoresis research, it also demonstrates the potential of this approach to predict the feasibility of iontophoretic transport across the skin
Noninvasive and minimally invasive methods for transdermal glucose monitoring
Noninvasive and minimally invasive techniques for monitoring glucose via the skin are reviewed. These approaches rely either on the interaction of electromagnetic radiation with the tissue or on the extraction of fluid across the barrier. The structure and physiology of the skin make the technical realization of transdermal glucose monitoring a difficult challenge. The techniques involving transdermal fluid extraction circumvent and/or compromise the barrier function of skin's outermost and least permeable layer, the stratum corneum, by the application of physical energy. While sonophoresis and microporation methods, for example, are in relatively early-stage development, a device using reverse iontophoresis [the GlucoWatch Biographer (Cygnus, Inc., Redwood City, CA)] is already commercially available. Optical techniques to monitor glucose are truly noninvasive. The tissue is irradiated, the absorbed or scattered radiation is analyzed, and the information is processed, to provide a measure proportional to the concentration of glucose in the dermal tissue. These techniques include near-infrared and Raman spectroscopy, polarimetry, light scattering, and photoacoustic spectroscopy. By contrast, impedance spectroscopy measures changes in the dielectric properties of the tissue induced by blood glucose variation. Large-scale studies in support of efficacy of these methodologies are as yet unavailable. At present, therefore, transdermal fluid extraction technologies are offering greater promise in terms of practical and realizable devices for patient use. The truly noninvasive allure of the optical approach assures continued and intense research activity--for the moment, however, an affordable, efficient, and portable system is not on the immediate horizon