A Review on Chemical Permeation Enhancers used in the Formulation of Transdermal Drug Delivery System

Skin penetration enhancement technology is a rapidly evolving area that will greatly increase the quantity of transdermal drug delivery medications. Penetration enhancers are used to facilitate the movement of drugs through the skin barrier. Numerous methods exist for extending partition enhancement. The enhancers' contact with the polar head of the lipid groups is the potential means for increasing the penetration. Penetration enhancers improve the amount of free water molecules between the bilayer, leading to an improvement of the polar drug diffusion cross section. This article focuses on the different compounds assessed for improving penetration activity like sulphoxides, azones, pyrrolidones, alcohols and alkanols, glycols, surfactants and terpenes.

Transferosomes as a Novel Therapeutic Delivery System: A Review

The poor penetration rate of the skin as a natural barrier makes transdermal drug delivery problematic. To increase transdermal dispersion of bioactives, electrophoresis, iontophoresis, chemical permeation enhancers, microneedles, sonophoresis, and vesicular systems such as liposomes, niosomes, elastic liposomes such as ethosomes, and transferosomes have all been used. Among these, transferosomes appear to be a promising option. Transferosomes are elastomeric or deformable vesicles that were originally discovered in the early 1990s. They're novel vesicular drug carrier system composed of phospholipid, surfactant, and water that improves transdermal drug delivery. Because of their low toxicity, biodegradability, ability to encapsulate both hydrophilic and lipophilic molecules, ability to prolong the drug's existence in the systemic circulation by encapsulation in vesicles, ability to target organs and tissues, and ability to reduce drug toxicity while increasing bioavailability, these vesicles are preferred over others. These vesicles undergo deformation, changes its shape and easily penetrates through the skin pores. There are two phases in any technique for preparing transferosomes. First, a thin film is hydrated before being sonicated to the required size; next, sonicated vesicles are homogenized by extrusion through a polycarbonate membrane. Transferosomes are evaluated for its entrapment efficiency, their drug content , in-vitro drug release, degree of deformability, turbidity, surface charge and morphology. Transferosomes are said to have a number of applications like delivery of vaccines,proteins, Anti-cancer drugs,anesthetics,herbal drugs and has better patient compliance,improved bio-availability and site-specific delivery and can serve as an emerging tool for transdermal delivery of almost all drugs and bio-actives.

Improvement of Resveratrol Permeation through Sublingual Mucosa: Chemical Permeation Enhancers versus Spray Drying Technique to Obtain Fast-Disintegrating Sublingual Mini-Tablets

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation.

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.

Delivery of Insulin via Skin Route for the Management of Diabetes Mellitus: Approaches for Breaching the Obstacles

Insulin is used for the treatment of diabetes mellitus, which is characterized by hyperglycemia. Subcutaneous injections are the standard mode of delivery for insulin therapy; however, this procedure is very often invasive, which hinders patient compliance, particularly for individuals requiring insulin doses four times a day. Furthermore, cases have been reported of sudden hypoglycemia occurrences following multidose insulin injections. Such an invasive and intensive approach motivates the quest for alternative, more user-friendly insulin administration approaches. For example, transdermal delivery has numerous advantages, such as prolonged drug release, low variability in the drug plasma level, and improved patient compliance. In this paper, the authors summarize different approaches used in transdermal insulin delivery, including microneedles, chemical permeation enhancers, sonophoresis, patches, electroporation, iontophoresis, vesicular formulations, microemulsions, nanoparticles, and microdermabrasion. Transdermal systems for insulin delivery are still being widely researched. The conclusions presented in this paper are extracted from the literature, notably, that the transdermal route could effectively and reliably deliver insulin into the circulatory system. Consistent progress in this area will ensure that some of the aforementioned transdermal insulin delivery systems will be introduced in clinical practice and commercially available in the near future.

Skin Permeation of Nanoparticles: Mechanisms Involved and Critical Factors Governing Topical Drug Delivery

Transdermal route has been an ever sought-after means of drug administration, regarded as being the most convenient and patient compliant. However, skin poses a great barrier to the entry of the external particles including bacteria, viruses, allergens, and drugs as well (mostly hydrophilic or high molecular weight drugs), consequent to its complex structure and composition. Among the various means of enhancing drug permeation through the skin, e.g. chemical permeation enhancers, electroporation, thermophoresis, etc. drug delivery through nanoparticles has been of great interest. Current literature reports a vast number of nanoparticles that have been implicated for drug delivery through the skin. However, a precise account of critical factors involved in drug delivery and mechanisms concerning the permeation of nanoparticles through the skin is necessary. The purpose of this review is to enumerate the factors crucial in governing the prospect of drug delivery through skin and classify the skin permeation mechanisms of nanoparticles. Among the various mechanisms discussed are the ones governed by principles of kinetics, osmotic gradient, adhesion, hydration, diffusion, occlusion, electrostatic interaction, thermodynamics, etc. Among the most common factors affecting skin permeation of nanoparticles that are discussed include size, shape, surface charge density, composition of nanoparticles, mechanical stress, pH, etc.

Transmucosal Absorption Enhancers in the Drug Delivery Field

Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes. To date, only a small number of permeation enhancers have progressed to clinical trials, and only one product that includes a permeation enhancer has reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Transmucosal Absorption Enhancers in the Drug Delivery Field (https://www.mdpi.com/journal/pharmaceutics/special_issues/transmucosal_absorption_enhancers). The guest editors outline the scope of the issue, reflect on the results and the conclusions of the 19 articles published in the issue and provide an outlook on the use of permeation enhancers in the drug delivery field.

Ionic Liquids as Potential and Synergistic Permeation Enhancers for Transdermal Drug Delivery

Transdermal drug delivery systems (TDDS) show clear advantages over conventional routes of drug administration. Nonetheless, there are limitations to current TDDS which warrant further research to improve current TDD platforms. Spurred by the synthesis of novel biodegradable ionic liquids (ILs) and favorable cytotoxicity studies, ILs were shown to be a possible solution to overcome these challenges. Their favorable application in overcoming challenges ranging from synthesis, manufacture, and even therapeutic benefits were documented. In this review, said ILs are highlighted and their role in TDDS is reviewed in terms of (a) ILs as permeation enhancers (single agents or combined), (b) ILs in drug modification, and (c) ILs as active pharmaceutical ingredients. Furthermore, future combination of ILs with other chemical permeation enhancers (CPEs) is proposed and discussed.