Microemulsions are thermodynamically stable colloidal dispersions of water and oil stabilized by a surfactant and, in many cases, also a cosurfactant. In the pharmaceutical field, microemulsions have been used as drug carriers for percutaneous, ocular, oral and parenteral administration. This review discusses some of the applications of microemulsions specifically for topical and transdermal applications. Microemulsion nomenclature and composition, with particular emphasis on choice of surfactant and cosurfactant, is discussed. Methods used to characterize microemulsions are reviewed. Microemulsion formulations for dermal and transdermal delivery of pharmaceutical agents with particular emphasis on anti-inflammatory and anaesthetic agents are critically evaluated. Finally, the issues which warrant further investigation by researchers in order to realize the full potential of the technology are discussed.

A good understanding of infant skin should provide a rationale for optimum management of the health of this integument. In this review, we discuss the skin barrier function of infants, particularly with reference to the use of diapers and baby wipes. The skin barrier of newborns continues to develop with age. Two years after birth, the barrier properties of infant skin closely resemble those of adult skin. However, several risk factors may contribute to impaired skin barrier and altered skin permeability in infants. Problems may arise from the use of diapers and baby wipes. The skin covered by a diaper is effectively an occluded environment, and thus is vulnerable to over-hydration. To date there has been no published information regarding dermal absorption of ingredients contained in baby wipes. Similarly, dermal absorption of topical ingredients in infants with underlying skin conditions has not been widely explored. Clearly, there are serious ethical concerns related to conducting skin permeation studies on infant skin. However, the increasing availability of non-invasive methods for in vivo studies is encouraging and offers new directions for studying this important patient group.

Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecules, with results expressed as arbitrary units of signal intensity. Clearly, this posed challenges for using CRS to determine skin delivery and to assess the drug bioavailability and bioequivalence of topical formulations. In the present work, the permeation of niacinamide (NIA) from various formulations in human skin was studied in vitro using conventional Franz cells and in vivo using a quantitative CRS method under finite dose conditions. The selection of NIA was based on its wide use in pharmaceutical and personal care formulations for many years. This is the first fully quantitative study to compare these methods. The vehicles investigated were neat Transcutol^® P (TC); binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML); and ternary mixtures of PG, PGML, and isopropyl myristate (IPM). These solvents were selected to encompass a range of physicochemical properties. NIA permeation was evident from all formulations in vitro and in vivo. The vehicles PG:PGML and PG:PGML:IPM delivered comparable amounts across the skin in vitro at 24 h (100.3–106.7 µg/cm², p > 0.05) that were significantly higher compared with those of TC (1.3 µg/cm², p < 0.05). An excellent in vitro in vivo correlation (R² = 0.98) was found following the linear regression of the cumulative amounts of NIA permeated in vitro and the amounts of NIA at 2 μm in the skin measured with CRS. A very good correlation between the cumulative permeation of NIA in vitro and the total amount of NIA that penetrated the stratum corneum (SC) per unit of surface area (μg/cm²) in vivo was also observed, with a Pearson correlation coefficient (R²) of 0.94. The findings support the use of CRS for the quantitative measurement of actives delivered to the skin in vivo. Future studies will focus on exploring the reproducibility and reliability of the method by investigating the delivery of different actives from a wider range of vehicles. Additionally, quantitative CRS will be evaluated further as a method for assessing the bioequivalence of topical formulations.

This review considers the role of in vitro permeation testing (IVPT) for the evaluation of drug delivery from topical formulations applied to the skin. The technique was pioneered by Franz in the 1970's and today remains an important tool in the development, testing and optimization of such topical formulations. An overview of IVPT as well as selection of skin for the experiment, integrity testing of the membrane, and required number of replicate skin samples is discussed. In the literature many researchers have focused solely on permeation and have not reported amounts of the active remaining on and in the skin at the end of the IVPT. Therefore, a particular focus of this article is determination of the complete mass balance of the drug. It is noteworthy that for the evaluation of bioequivalence of topical formulations the draft guideline issued by the European Medicines Agency (EMA) requires the IVPT method to report on both the skin deposition and distribution of the active in the skin as well as amount permeated. Other aspects of current guidance from the EMA and United States Food and Drug Agency for IVPT are also compared and contrasted. Ultimately, harmonisation of IVPT protocols across the regulatory agencies will expedite the development process for novel topical formulations as well as the availability of generic products.

Ion pairing is a strategy used to increase the permeation of topically applied ionised drugs. Formation occurs when the electrostatic energy of attraction between oppositely charged ions exceeds their mean thermal energy, making it possible for them to draw together and attain a critical distance. These ions then behave as a neutral species, allowing them to partition more readily into a lipid environment. Partition coefficient studies may be used to determine the potential of ions to pair and partition into an organic phase but cannot be relied upon to predict flux. Early researchers indicated that temperature, size of ions and dielectric constant of the solvent system all contributed to the formation of ion pairs. While size is important, this may be outweighed by improved lipophilicity of the counter ion due to increased length of the carbon chain. Organic counter ions are more effective than inorganic moieties in forming ion pairs. In addition to being used to increase permeation, ion pairs have been used to control and even prevent permeation of the active ingredient. They have also been used to stabilise solid lipid nanoparticle formulations. Ion pairs have been used in conjunction with permeation enhancers, and permeation enhancers have been used as counter ions in ion pairing. This review attempts to show the various ways in which ion pairs have been used in drug delivery via the skin. It also endeavours to extract and consolidate common approaches in order to inform future formulations for topical and transdermal delivery.