Development of Topical/Transdermal Self-Emulsifying Drug Delivery Systems, Not as Simple as Expected

Abstract

Self-emulsifying drug delivery systems (SEDDSs) originated as an oral lipid-based drug delivery system with the sole purpose of improving delivery of highly lipophilic drugs. However, the revolutionary drug delivery possibilities presented by these uniquely simplified systems in terms of muco-adhesiveness and zeta-potential changing capacity lead the way forward to ground-breaking research. Contrarily, SEDDSs destined for topical/transdermal drug delivery have received limited attention. Therefore, this review is focused at utilising principles, established during development of oral SEDDSs, and tailoring them to fit evaluation strategies for an optimised topical/transdermal drug delivery vehicle. This includes a detailed discussion of how the authentic pseudo-ternary phase diagram is employed to predict phase behaviour to find the self-emulsification region most suitable for formulating topical/transdermal SEDDSs. Additionally, special attention is given to the manner of characterising oral SEDDSs compared to topical/transdermal SEDDSs, since absorption within the gastrointestinal tract and the multi-layered nature of the skin are two completely diverse drug delivery territories. Despite the advantages of the topical/transdermal drug administration route, certain challenges such as the relatively undiscovered field of skin metabolomics as well as the obstacles of choosing excipients wisely to establish skin penetration enhancement might prevail. Therefore, development of topical/transdermal SEDDSs might be more complicated than expected.

Development of a Self-Emulsifying Drug Delivery System for Optimized Topical Delivery of Clofazimine

“…The simplicity and ease of the preparation technique compared to methods followed to manufacture liposomes and nano-emulsions sets topical SEDDSs apart from current topical/transdermal drug delivery systems, especially when considering industrial upscaling and the possibility of individualized therapy. We would like to emphasize the potential of topical/transdermal SEDDSs to aid in diseases worsened by lymphatic dissemination, including Human Immunodeficiency Virus, metastatic cancers and endogenous extra-pulmonary TB, due to the lipid-based nature of SEDDSs potentially favorable for lymphatic uptake via topical application [ 108 , 109 , 110 , 111 ].…”

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology

“…The gel was formulated by dispersing the self-nanoemulsifying preconcentrate in water containing the gelling agent [ 18 , 19 , 21 ]. Pluronic ® F127 (20% w / w ) was dissolved in cold water.…”

“…Modulation of the lipid arrangement of the stratum corneum is easily achieved by the oils and surfactants present in topical, self-emulsifying drug delivery systems. Furthermore, they also facilitate solubilization and partitioning of lipophilic actives in the skin layers [ 18 , 19 ]. To improve adhesion, the viscosity of nanoemulsion is increased by the addition of a gelling agent to form a nanoemulgel, which makes it easy and convenient for transcutaneous application.…”

Novel Self-Nano-Emulsifying Drug Delivery Systems Containing Astaxanthin for Topical Skin Delivery

“…SNEDDS are isotropic mixtures of an active compound in a combination of lipids, surfactants, and hydrophilic co-solvents/solubilizers that produce spontaneous ultrafine emulsions upon gentle agitation in the water phase (typically <50 nm in size) [ 32 , 33 , 34 ]. SNEDDS have a high solubilizing capacity for lipophilic compounds, are thermodynamically stable, provide simplicity of fabrication, and have an elegant appearance [ 35 , 36 ]. They have been shown to enhance skin delivery of lipophilic solutes such as curcumin [ 37 ] and clofazimine [ 38 ].…”