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Pharmaceutics
Special Issues
Transdermal Drug Delivery Systems
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Transdermal Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (20 February 2020) | Viewed by 37890

Special Issue Editors

Prof. Dr. Kenji Sugibayashi

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Guest Editor
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan
Interests: skin permeation; skin concentration; transdermal delivery; hair follicle delivery; layered application; topical formulation; liquid crystal; alternative animal experiment; cultured human skin model; iontophoresis
Special Issues, Collections and Topics in MDPI journals
Prof. Hiroaki Todo

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Guest Editor
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan
Interests: skin permeation; skin concentration; transdermal delivery; hair follicle delivery; layered application; topical formulation; liquid crystal; alternative animal experiment; cultured human skin model; iontophoresis

Special Issue Information

Dear Colleagues,

The skin permeation rate of drugs is generally slow; accordingly, drugs applied as Transdermal Delivery Systems (TDS) are limited to about 20. Early works on TDS mostly focused on enhancing drug permeability through the stratum corneum to pave the way for TDS-containing drugs of varying physicochemical properties. At the peak of TDS, membrane-controlled or diffusion-controlled matrix patches were developed; however, drug-in-adhesive has become more common at present. Initially, hydrophobic silicone or acrylic pressure-sensitive adhesives were used for earlier patches. Recent developments employs technology allowing for the inclusion of sodium salts and hydrochlorides, and even considerable amounts of water in the hydrophobic patches. At the same time, there is a growing interest in skin-penetration-enhancing methods using external energy, such as iontophoresis, electroporation, phonophoresis, and thermal perforation. Microneedles and needleless injection have gained considerable advancement as well. Among them are the clinical application of iontophoresis to several medicines and cosmetics, and it is worth mentioning that microneedles are also being used in the cosmetics field. Indeed, the merging of pharmaceutical formulations and medical devices has become the springboard for TDS research.This Special Issue will provide readers with an overview of the current advances in the field of transdermal delivery for low-molecular-weight drugs and mid-to-high molecular drugs as well.

Prof. Hiroaki Todo
Prof. Kenji Sugibayashi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Transdermal drug delivery
  • Skin delivery
  • Dermal patch
  • Penetration enhancer
  • Iontophoresis
  • Microneedles

Published Papers (6 papers)

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Research

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16 pages, 2439 KiB  
Article
Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl
by Santosh Bashyal, Chang Yell Shin, Sang Min Hyun, Sun Woo Jang and Sangkil Lee
Pharmaceutics 2020, 12(3), 270; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12030270 - 16 Mar 2020
Cited by 21 | Viewed by 5061
Abstract
Transdermal delivery systems are emerging platforms for the delivery of donepezil hydrochloride (DH) for treating Alzheimer’s disease. The primary aim of this study was to develop polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels and to evaluate their feasibility for delivering DH via a [...] Read more.
Transdermal delivery systems are emerging platforms for the delivery of donepezil hydrochloride (DH) for treating Alzheimer’s disease. The primary aim of this study was to develop polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels and to evaluate their feasibility for delivering DH via a transdermal route. Physicochemical properties, such as gel fraction (%), swelling ratio (%), weight loss (%), mechanical strength, elongation at break, and Young’s modulus of the prepared hydrogels were evaluated. Furthermore, in vitro skin permeation and in vivo pharmacokinetic studies were performed. With an increased concentration of propylene glycol (PG), the gel fraction (%), maximum strength, and elongation at break decreased. However, the swelling ratio (%) and weight loss (%) of hydrogels increased with increased PG content. The 26% PG-hydrogel was superior, with an enhancement ratio of 12.9 (*** p < 0.001). In addition, the 11% PG-hydrogel and 1% PG-hydrogel exhibited an enhancement ratio 6.30-fold (*** p < 0.001) and 2.85-fold (* p < 0.05) higher than that exhibited by control, respectively, indicating a promising effect of PG on skin permeation. In addition, in vivo pharmacokinetic studies on hairless rats assessed the expediency for transdermal delivery of DH. The transdermal delivery of optimized hydrogel-patches with two different doses of DH revealed that the maximum plasma concentration and area under the curve were dose dependent, and the time to reach the maximum concentration was 8 h. Thus, optimized hydrogels have the potential to enhance the transdermal delivery of DH and could be a novel clinical approach. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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10 pages, 2249 KiB  
Article
A Mixed Micellar Formulation for the Transdermal Delivery of an Indirubin Analog
by Seol Hwa Seo, Eunhwan Kim, Yechan Joo, Juseung Lee, Kyung Taek Oh, Sung-Joo Hwang and Kang-Yell Choi
Pharmaceutics 2020, 12(2), 175; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12020175 - 19 Feb 2020
Cited by 17 | Viewed by 3330
Abstract
Indirubin is an active component of Dang Gui Long Hui Wan, which has been used in traditional Chinese medicine to treat inflammatory diseases as well as for the prevention and treatment of human cancer, such as chronic myeloid leukemia. The therapeutic effects of [...] Read more.
Indirubin is an active component of Dang Gui Long Hui Wan, which has been used in traditional Chinese medicine to treat inflammatory diseases as well as for the prevention and treatment of human cancer, such as chronic myeloid leukemia. The therapeutic effects of indirubin analogs have been underestimated due to its poor water solubility and low bioavailability. To improve the solubility and bioavailability of indirubin analogs, we prepared a mixed micellar formulation with Kolliphor® EL and Tween 80 as surfactants, and PEG 400 as a co-surfactant, followed by complexation with (2-hydroxyproply)-β-cyclodextrin at appropriate ratios. Overall, improving the solubility and skin penetration of indirubin analogs can increase clinical efficacy and provide maximum flux through the skin. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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11 pages, 1287 KiB  
Article
Usefulness of Artificial Membrane, Strat-M®, in the Assessment of Drug Permeation from Complex Vehicles in Finite Dose Conditions
by Florencio Jr Arce, Narumi Asano, Gerard Lee See, Shoko Itakura, Hiroaki Todo and Kenji Sugibayashi
Pharmaceutics 2020, 12(2), 173; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12020173 - 19 Feb 2020
Cited by 37 | Viewed by 4474
Abstract
The ban on the use of animals in testing cosmetic products has led to the development of animal-free in vitro methods. Strat-M® is an artificial membrane engineered to mimic human skin and is recommended as a replacement for skin. However, its usefulness [...] Read more.
The ban on the use of animals in testing cosmetic products has led to the development of animal-free in vitro methods. Strat-M® is an artificial membrane engineered to mimic human skin and is recommended as a replacement for skin. However, its usefulness in the assessment of the permeation of cosmetics in in-use conditions remains unverified. No data have been published on its comparative performance with the membrane of choice, porcine skin. The comparative permeability characteristics of Strat-M® and porcine skin were investigated using Franz diffusion cells. Caffeine (CF) and rhododendrol (RD) in complex vehicles with varying concentrations of polyols were applied as finite and infinite doses. Good rank orders of permeation from finite dose experiments were observed for RD. High correlations were observed in RD permeation between Strat-M® and porcine skin under finite and infinite dose conditions, whereas only finite dose conditions for CF were associated with good correlations. Permeation from formulations with high polyol content and residual formulations was enhanced due to the disruption of the integrity of the Strat-M® barrier. The usefulness of Strat-M® in the assessment of dermal permeation may be limited to finite dose conditions and not applicable to infinite dose conditions or formulations applied in layers. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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15 pages, 2430 KiB  
Article
Preparation and Evaluation of Atorvastatin-Loaded Nanoemulgel on Wound-Healing Efficacy
by Mohamed A. Morsy, Rania G. Abdel-Latif, Anroop B. Nair, Katharigatta N. Venugopala, Amira F. Ahmed, Heba S. Elsewedy and Tamer M. Shehata
Pharmaceutics 2019, 11(11), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11110609 - 13 Nov 2019
Cited by 67 | Viewed by 7410
Abstract
Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. The potential of various statins including atorvastatin (ATR) to improve the wound healing effect was established. The aim of this study was to formulate and evaluate [...] Read more.
Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. The potential of various statins including atorvastatin (ATR) to improve the wound healing effect was established. The aim of this study was to formulate and evaluate the efficacy of topical application of ATR-based nanoemulgel on wound healing. The prepared formulations (ATR gel, ATR emulgel, and ATR nanoemulgel) were evaluated for their physical appearance, rheological behavior, in vitro drug release and ex vivo drug permeation. The in vivo wound healing effect was evaluated in wound-induced rats. The prepared ATR gel formulations showed good physical properties and were comparable. The release profiles of drugs from gel, emulgel, and nanoemulgel were distinct. Skin permeation potential of ATR was significantly (p < 0.05) enhanced when formulated into nanoemulgel. In vivo wound healing studies showed that ATR nanoemulgel exhibited the highest percent wound contraction. Histopathological assessment showed marked improvement in the skin histological architecture after 21 days of ATR nanoemulgel treatment. In conclusion, the data demonstrated here signify the prospective of ATR nanoemulgel as an innovative therapeutic approach in wound healing. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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Review

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25 pages, 1921 KiB  
Review
Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities
by Rabin Neupane, Sai H.S. Boddu, Jwala Renukuntla, R. Jayachandra Babu and Amit K. Tiwari
Pharmaceutics 2020, 12(2), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12020152 - 13 Feb 2020
Cited by 182 | Viewed by 10499
Abstract
The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. [...] Read more.
The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. The assessment of ex vivo permeation during the pharmaceutical development process helps in understanding the product quality and performance of a transdermal delivery system. Generally, excised human skin relevant to the application site or animal skin is recommended for ex vivo permeation studies. However, the limited availability of the human skin and ethical issues surrounding the use of animal skin rendered these models less attractive in the permeation study. In the last three decades, enormous efforts have been put into developing artificial membranes and 3D cultured human skin models as surrogates to the human skin. This manuscript provides an insight on the European Medicines Agency (EMA) guidelines for permeation studies and the parameters affected when using Franz diffusion cells in the permeation study. The need and possibilities for skin alternatives, such as artificially cultured human skin models, parallel artificial membrane permeability assays (PAMPA), and artificial membranes for penetration and permeation studies, are comprehensively discussed. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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29 pages, 2164 KiB  
Review
Bio-Functional Textiles: Combining Pharmaceutical Nanocarriers with Fibrous Materials for Innovative Dermatological Therapies
by Daniele Massella, Monica Argenziano, Ada Ferri, Jinping Guan, Stéphane Giraud, Roberta Cavalli, Antonello A. Barresi and Fabien Salaün
Pharmaceutics 2019, 11(8), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11080403 - 11 Aug 2019
Cited by 30 | Viewed by 6213
Abstract
In the field of pharmaceutical technology, significant attention has been paid on exploiting skin as a drug administration route. Considering the structural and chemical complexity of the skin barrier, many research works focused on developing an innovative way to enhance skin drug permeation. [...] Read more.
In the field of pharmaceutical technology, significant attention has been paid on exploiting skin as a drug administration route. Considering the structural and chemical complexity of the skin barrier, many research works focused on developing an innovative way to enhance skin drug permeation. In this context, a new class of materials called bio-functional textiles has been developed. Such materials consist of the combination of advanced pharmaceutical carriers with textile materials. Therefore, they own the possibility of providing a wearable platform for continuous and controlled drug release. Notwithstanding the great potential of these materials, their large-scale application still faces some challenges. The present review provides a state-of-the-art perspective on the bio-functional textile technology analyzing the several issues involved. Firstly, the skin physiology, together with the dermatological delivery strategy, is keenly described in order to provide an overview of the problems tackled by bio-functional textiles technology. Secondly, an overview of the main dermatological nanocarriers is provided; thereafter the application of these nanomaterial to textiles is presented. Finally, the bio-functional textile technology is framed in the context of the different dermatological administration strategies; a comparative analysis that also considers how pharmaceutical regulation is conducted. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery Systems)
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