Metamorphosis of Vehicles: Mechanisms and Opportunities

Abstract

The visibility of a skin condition or dermatosis led to the reasonable assumption that the direct application of a therapeutic remedy to the target tissue holds many advantages. Through centuries, the nomenclature of topical preparations has proliferated and finally been moulded into the compulsory nomenclature of official compendia. In everyday life, many terms have been added and have complicated understanding and communication among and between healthcare professionals and laypersons. A large proportion of marketed topical preparations contain significant amounts of volatile vehicle ingredients that evaporate once they are applied onto the skin, that is, the vehicle format as well as the sum of vehicle ingredients in the primary container are different from the vehicle format and the sum of vehicle ingredients on the skin. This phenomenon and the potential consequences have so far been often ignored by many healthcare professionals and laypersons. To gain a better understanding, this phenomenon has been coined as the metamorphosis of the vehicle. The metamorphosis of the vehicle describes the vehicle (a) in the primary container (primary formulation), (b) during and immediately after application onto the skin (secondary formulation) and (c) after all volatile vehicle ingredients have evaporated from the vehicle on top of the skin (tertiary or residual formulation). The secondary and tertiary formulations may offer increased delivery of cosmetic or pharmaceutical actives. This is achieved by (a) an intended post-application creation of supersaturation of actives in the secondary and tertiary formulations or by (b) physico-chemical triggers such as pH.

Topical corticosteroid vehicle composition and implications for clinical practice

“…The vehicle composition of a TCS product affects the degree of dermatosis response, 16 plus the safety and cosmetic acceptability of the TCS (Table 1). 1,14,17,18 It governs the TCS penetration concentration gradient, 8,12,15 TCS solubility 1,8,9,15 (Table 1) and ability to transiently alter skin status (Table 2). 1,15 This controls the extent of TCS penetration and permeation 8,9,14,15 .…”

“…However, it is misleading to assume that a product’s primary vehicle format is responsible. Depending on the product, the vehicle format and composition may change dramatically during and after application, which can create a steeper concentration gradient for TCS penetration and permeation 1,8 . A striking example is the application of TCS as a foam, in which the product metamorphosizes from its primary vehicle format (subsaturated with TCS), into its secondary format (saturated with TCS as the volatile ingredients evaporate) and lastly, its tertiary format (supersaturated with TCS as all volatile ingredients have evaporated) (Fig.…”

“…1,14,17,18 It governs the TCS penetration concentration gradient, 8,12,15 TCS solubility 1,8,9,15 (Table 1) and ability to transiently alter skin status (Table 2). 1,15 This controls the extent of TCS penetration and permeation 8,9,14,15 . Consequently, brand‐name and generic products possessing the same TCS, concentration and vehicle format may have different relative potencies and cosmetic features 16 .…”

“…A TCS can only penetrate and permeate the skin if it is in a dissolved state and more soluble in the skin than its vehicle 8,9 …”

Preparation of Topical Itraconazole with Enhanced Skin/Nail Permeability and In Vivo Antifungal Efficacy against Superficial Mycosis

“…Therefore, incorporation of volatile vehicles may be a suitable alternative approach in topical ITZ solution development. Additionally, the volatile vehicle used in topical formulations has been reported to follow the metamorphism phenomenon, which leads to drug supersaturation within the vehicle system at the applied area over time, which can increase both effective and immediate drug delivery [ 14 ]. The incorporation of a permeation enhancer, which interacts with lipid and protein constituents present in the outermost layer of skin, can increase drug penetration and partitioning [ 15 ].…”