Abstract(Trans)dermal drug therapy is gaining increasing importance in the modern drug development. To fully utilize the potential of this route, it is important to optimize the delivery of active ingredient/drug into/through the skin. The optimal carrier/vehicle can enhance the desired outcome of the therapy therefore the optimization of skin formulations is often included in the early stages of the product development. A rational approach in designing and optimizing skin formulations requires well-defined skin models, able to identify and evaluate the intrinsic properties of the formulation. Most of the current optimization relies on the use of suitable ex vivo animal/human models.However, increasing restrictions in use and handling of animals and human skin stimulated the search for suitable artificial skin models. This review attempts to provide an unbiased overview of the most commonly used models, with emphasis on their limitations and advantages. The choice of the most applicable in vitro model for the particular purpose should be based on the interplay between the availability, easiness of the use, cost and the respective limitations.

The texture properties of formulation are an important parameter in optimization of topical formulations. These properties will affect applicability of the formulation at the administration site and therapy outcome. Our aim was to develop a fast and reliable method to characterize texture properties of hydrogels, namely cohesiveness, adhesiveness, and hardness. During the method development, we realized that the measurements setup needed to be adjusted for each hydrogel type, namely Carbopol, chitosan, and poloxamer hydrogels. The influence of the polymer concentration, pH, and incorporation of additives such as glycerol, drug solution, or liposomes on the texture properties, as determined by Texture Analyzer, was evaluated. In addition, the new method was applied to determine the changes during the accelerated stability testing. While Carbopol and poloxamer gels showed a linear relationship between the polymer concentration and texture properties, for low molecular weight chitosan gels the properties increased in exponential manner with increasing polymer concentration. The effect of incorporated liposomes on the gel properties was found to be dependent on the type of hydrogel. The hydrogel hardness was affected by the temperature as seen in accelerated stability testing. The method represents a valuable tool in pharmaceutical and cosmetics formulation development. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

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Penetration potential of vesicles destined for trans(dermal) administration remains to be of great interests both in respect to drug therapy and cosmetic treatment. This study investigated the applicability of the phospholipid vesicle-based permeation assay (PVPA) as a novel in vitro skin barrier model for screening purposes in preformulation studies. Various classes of liposomes containing hydrophilic model drug were examined, including conventional liposomes (CLs), deformable liposomes (DLs) and propylene glycol liposomes (PGLs). The size, surface charge, membrane deformability and entrapment efficiency were found to be affected by the vesicle lipid concentration, the presence of the surfactant and propylene glycol. All liposomes exhibited prolonged drug release profiles with an initial burst effect followed by a slower release phase. The permeation of the drug from all of the tested liposomes, as assessed with the mimicked stratum corneum--PVPA model, was significantly enhanced as compared to the permeability of the drug in solution form. Although the DLs and the PGLs exhibited almost the same membrane elasticity, the permeability of the drug delivered by PGLs was higher (6.2 × 10⁻⁶ cm/s) than DLs (5.5 × 10⁻⁶ cm/s). Therefore, this study confirmed both the potential of liposomes as vesicles in trans(dermal) delivery and potential of the newly developed skin-PVPA for the screening and optimization of liposomes at the early preformulation stage.

Cost-effective and efficient methods for permeability screening are crucial during early development of drugs, drug formulations, and cosmeceuticals. Alternatives to animal experiments are impelled for both economical and ethical reasons. The aim of this study was to determine the ability of the phospholipid vesicle-based permeation assay (PVPA) to assess the effect of different formulations on drug permeability and thus establish its utility in formulation development. Three model drugs were tested in solutions and as liposomal formulations. The permeability results for the PVPA models were compared with the results for the reconstructed human skin model, EpiSkin(®). The drugs were ranked based on their estimated penetration potentials, and the results were in accordance with what was expected considering the physicochemical properties of the drugs. PVPAs (E-80, ceramide, cholesterol, cholesteryl sulfate, and palmitic acid) was able to distinguish between drug solutions and liposomal formulations; however, EpiSkin(®) detected only small differences between the drugs in solution and formulations. In contrast with EpiSkin(®), which is limited by a 3-day testing window, PVPA barriers can be stored frozen for up to 2 weeks or even up to 16 months, depending on their compositions. The PVPA models are thus more cost effective and efficient than the EpiSkin(®) model for permeability screening during early drug development.