Mangiferin and Hesperidin Transdermal Distribution and Permeability through the Skin from Solutions and Honeybush Extracts (Cyclopia sp.)-A Comparison Ex Vivo Study.

Polyphenolic compounds-mangiferin and hesperidin-are, among others, the most important secondary metabolites of African shrub Cyclopia sp. (honeybush). The aim of this study was to compare the percutaneous absorption of mangiferin and hesperidin from solutions (water, ethanol 50%, (v/v)) and extracts obtained from green and fermented honeybush (water, ethanol 50%, (v/v)). Research was performed with the Bronaugh cells, on human dorsal skin. The mangiferin and hesperidin distributions in skin layers (stratum corneum, epidermis, and dermis) and in acceptor fluid (in every 2, 4, 6, and 24 h) were evaluated by HPLC-Photodiode Array Coulometric and Coulometric Electrochemical Array Detection. The transdermal distribution of hesperidin was also demonstrated by fluorescence microscopy. Results indicated that mangiferin and hesperidin were able to cross the stratum corneum and penetrate into the epidermis and dermis. An advantage of hesperidin penetration into the skin from the water over ethanol solution was observed (451.02 ± 14.50 vs. 357.39 ± 4.51 ng/cm2), as well as in the mangiferin study (127.56 ± 9.49 vs. 97.23 ± 2.92 ng/cm2). Furthermore, mangiferin penetration was more evident from nonfermented honeybush ethanol extract (189.85 ± 4.11 ng/cm2) than from solutions. The permeation of mangiferin and hesperidin through the skin to the acceptor fluid was observed regardless of whether the solution or the honeybush extract was applied. The highest ability to permeate the skin was demonstrated for the water solution of hesperidin (250.92 ± 16.01 ng/cm2), while the hesperidin occurring in the extracts permeated in a very low capacity. Mangiferin from nonfermented honeybush ethanol extract had the highest ability to permeate to the acceptor fluid within 24 h (152.36 ± 8.57 ng/cm2).

Polymeric nanoparticles-embedded organogel for roxithromycin delivery to hair follicles.

Drug delivery into hair follicles with the use of nanoparticles (NPs) is gaining more importance as drug-loaded NPs may accumulate in hair follicle openings. The aim was to develop and evaluate a pluronic lecithin organogel (PLO) with roxithromycin (ROX)-loaded NPs for follicular targeting. Polymeric NPs were evaluated in terms of particle shape, size, zeta potential, suspension stability, encapsulation efficiency and in vitro drug release. Lyophilized NPs were incorporated into the PLO and rheological measurements of the nanoparticles-embedded organogels were done. The fate of the NPs in the skin was traced by incorporation of a fluorescent dye into the NPs. As a result, ROX was efficiently incorporated into polymeric NPs characterized by the appropriate size (approximately 300 nm) allowing drug delivery to hair follicles. In ex vivo human skin penetration studies, horizontal skin sections revealed fluorescence deep in the hair follicles. Although the organogel has higher affinity to the lipidic follicular area than an aqueous suspension of NPs, it did not seem to improve penetration of the NPs along the hair shaft. The results proved that it was possible to achieve preferential targeting to the pilosebaceous unit using polymeric NPs formulated either into the aqueous suspension or semisolid topical formulation.

Spray drying technique: II. Current applications in pharmaceutical technology.

This review presents current applications of spray drying in pharmaceutical technology. The topics discussed include the obtention of excipients and cospray dried composites, methods for increasing the aqueous solubility and bioavailability of active substances, and modified release profiles from spray-dried particles. This review also describes the use of the spray drying technique in the context of biological therapies, such as the spray drying of proteins, inhalable powders, and viable organisms, and the modification of the physical properties of dry plant extracts.

Effect of adhesive matrix composition and terpinolene on indomethacin bioavailability in rats from transdermal therapeutic system.

Drug-in-adhesive matrix-type transdermal therapeutic systems for indomethacin (IND) were formulated and evaluated. Silicone and two types of polyacrylates were used as the bases of matrices. Terpinolene was used as a penetration enhancer. The physicochemical properties of matrices were determined. The bioavailability study of IND was performed in rats. The presence of IND in blood was demonstrated for each system. The calculated pharmacokinetics parameters for IND mainly depend on the solubility of IND in the adhesive layer. The positive influence of a penetration enhancer on IND bioavailability was observed only for one type of polyacrylate matrices.

Ex vivo skin absorption of terpenes from Vicks VapoRub ointment.

BACKGROUND: The pharmaceutical market offers a wide range of inhalant drug products applied on the skin that contain essential oils and/or their isolated compounds, i.e. terpenes. Because there are few data concerning the skin penetration of terpenes, especially from complex carriers, the goal of this study was to determine the ex vivo skin absorption kinetics of chosen terpenes, namely eucalyptol, menthol, camphor, alpha-pinene, and beta-pinene, from the product Vicks VapoRub. MATERIAL/METHODS: Human cadaver skin was placed in a flow-through diffusion chamber and the product was applied for 15, 30, and 60 min. After the application time the skin was separated into layers using a tape-stripping technique: three fractions of stratum corneum and epidermis with dermis, and terpenes amounts in the samples were determined by gas-chromatography. RESULTS: The investigated terpenes showed different absorption characteristics related to their physicochemical properties and did not permeate through the skin into the acceptor fluid. Eucalyptol had the largest total accumulation in the stratum corneum and in the epidermis with dermis, while alpha-pinene penetrated into the skin in the smallest amount. CONCLUSIONS: The short time in which saturation of the stratum corneum with the terpenes occurred and the high accumulation of most of the investigated terpenes in the skin layers proved that these compounds easily penetrate and permeate the stratum corneum and that in vivo they may easily penetrate into the blood circulation.

Commentary to the article "Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro".

This note summarises recent studies on skin penetration of terpinen-4-ol, which is the main component of tea tree oil [S.E. Cross, M. Russell, I. Southwell, M.S. Roberts, Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro, Eur. J. Pharm. Biopharm. doi: 10.1016/j.ejpb.2007.10.002 (in press)]. The influence of different experimental models on obtained skin penetration results is discussed.

Skin penetration of terpenes from essential oils and topical vehicles.

The purpose of this study was to evaluate the in vitro cutaneous penetration of five terpenes--linalool, linalyl acetate, terpinen-4-ol, citronellol and alpha-pinene--applied in pure essential oils or in dermatological formulations (o/w emulsion, oily solution or hydrogel) containing 0.75 % w/w of the essential oils. Different skin absorption was observed depending on the type of the vehicle and terpenes' log P values. Cutaneous accumulation of terpenes is several times higher when they are applied in pure essential oils than in topical vehicles. Penetration of terpinen-4-ol to the skin was better from an oily solution (approximately 90 microg/cm (2)) than from an emulsion (60 microg/cm (2)). No penetration of linalyl acetate from topical vehicles into viable skin was observed, but also for this terpene penetration to the upper layers of the stratum corneum was 2-times higher when an oily solution was used. In contrast, the cutaneous absorption of linalool was the same from both vehicles (50-60 microg/cm (2)). The skin penetration of alpha-pinene was not traceable when it was applied in an oily solution. Only a small amount (approximately 5 microg/cm (2)) of this terpene was determined in viable skin after application as a hydrogel. Citronellol applied in a hydrogel penetrated into all skin layers in a total amount of 25 microg/cm (2), while no penetration into viable skin layers after application of an oily solution was noted. Only citronellol permeated into the acceptor medium.