Importance of a suitable working protocol for tape stripping experiments on porcine ear skin: Influence of lipophilic formulations and strip adhesion impairment.

The tape stripping method is a very important tool for dermopharmacokinetic experiments in vitro and the accurate measurement of the removed corneocytes is key for a reliable calculation of a drug's skin penetration behavior. Therefore, various methods to quantify the amount of corneocytes removed with each tape strip have been employed, ranging from gravimetric approaches to protein assays and recently near infrared densitometry (NIR) has become very widely used. As this method is based on a reduction of light intensity, interference of formulation components seems conceivable, as they could scatter light and change the results. In this study, NIR measurements were compared to a protein assay and in addition, the influence of highly lipophilic formulations on the results of tape stripping experiments was investigated as impairment of the adherence of strips has been reported. To this end, different tape stripping protocols were employed. The obtained results ensure suitability of the NIR method and moreover suggest a more pronounced influence on adherence with increasing lipophilicity in applied formulations. The results show that adaptation of the tape stripping protocol to the specifications of envisioned experiments is important for reliable results. Two protocols were found favorable and are presented in this work.

Size analysis of nanoparticles extracted from W/O emulsions.

Nanosized particles are frequently used in many different applications, especially TiO2 nanoparticles as physical filters in sunscreens to protect the skin from UV radiation. However, concerns have arisen about possible health issues caused by nanoparticles and therefore, the assessment of the occurrence of nanoparticles is important in pharmaceutical and cosmetic formulations. In a previous work of our group, a method was presented to extract nanoparticles from O/W emulsions. But to respond to the needs of dry and sensitive skin, sunscreens of the water-in-oil emulsion type are available. In these, assessment of present nanoparticles is also an important issue, so the present study offers a method for extracting nanoparticles from W/O emulsions. Both methods emanate from the same starting point, which minimizes both effort and cost before the beginning of the assessment. By addition of NaOH pellets and centrifugation, particles were extracted from W/O emulsions and measured for their size and surface area by laser diffraction. With the simple equation Q=A/S a distinction between nanoparticles and microparticles was achieved in W/O emulsions, even in commercially available samples. The present method is quick and easy to implement, which makes it cost-effective.

Influence of a multiple emulsion, liposomes and a microemulsion gel on sebum, skin hydration and TEWL.

OBJECTIVE: In this study, the influence of three cosmetically relevant, priorly characterized vehicles on skin hydration, sebum content and transepidermal water loss was investigated. The chosen vehicles included a liposomal pre-formulation, a multiple W/O/W emulsion and a microemulsion gel. The in vivo effects of these vehicles were demonstrated and compared among them. METHODS: The stability of the prepared vehicles was determined visually, microscopically, rheologically by pH measurements and particle size. Interactions with skin were assessed by non-invasive biophysical techniques using the Corneometer(®), Aqua Flux(®) and Sebumeter, measuring skin hydration, TEWL and skin sebum content, respectively. RESULTS: All vehicles remained stable over an observation period of 6 weeks. The multiple emulsion increased sebum content and skin hydration. In case of the liposomes, each monitored parameter remained almost constant. In contrast, the microemulsion gel lowered skin hydration and increased TEWL values, but even 1 week after termination of the treatment TEWL decreased almost close to control levels. CONCLUSION: All produced vehicles were proven to remain physically stable over the duration of this study. The used multiple emulsion showed very skin-friendly properties by increasing sebum and skin hydration. Likewise, the liposomal pre-formulation exhibited no negative effects. On the contrary, the investigated microemulsion gel seemed to have skin dehydrating and TEWL increasing features. However, the multiple emulsion as well as liposomes was identified to be well-tolerated vehicles for skin which might qualify them for the use in cosmetic formulations.

Dilution of semi-solid creams: influence of various production parameters on rheological properties and skin penetration.

UNLABELLED: In order to customise treatment for patients, topical formulations are often diluted with drug-free cream bases to adjust the drug dose and thereby the formulations' activity to the patients' needs. However, the process of dilution influences properties of the formulations. Stability can be reduced as well as the microbial stability and most importantly, efficacy and skin penetration behaviour can be severely and unpredictably changed. The present study investigates the effects of production parameters on creams, namely incorporation of an API (active pharmaceutical ingredients) into an OW cream with prior mixing with propylene glycol or without and subsequent automated or manual dilution of the resulting creams with three different cream bases. Effects were measured by influence on microscopic appearance, measurement of chemical stability, skin penetration and rheological behaviour. RESULT: suggest strong influence of the cream bases used for dilution of the formulations. Mixture of equal amounts of the employed OW and WO cream proved unfavourable due to inferior penetration behaviour and less appealing microscopic and macroscopic appearance. Prior mixing with PG was of negligible importance for the characteristics of the dilutions, however, the type of API and manner of dilution had an influence on the viscosity of the formulations.

Size analysis of nanoparticles in commercial O/W sunscreens.

Nanoparticles are employed in a variety of applications and especially in cosmetics the issue is discussed whether or not they can be regarded as safe. Analysis of nanosized structures and morphology studies prove to be difficult in many aspects. Nevertheless, there is the demand for new, cost-effective and simple yet reliable methods of analysis to assess the occurrence of nanoparticles in cosmetics in order to evaluate the possible risks conditioned by nanosized structures. In the present study, a simple method was developed to extract particles from commercial sunscreens that are O/W emulsions to measure the particle size of suspended material by laser diffraction. A following, simple calculation based on the specific surface area and particle size distribution allows distinguishing agglomerated nanoparticles from larger particles and thereby contributes well to the tools in analysis of cosmetic products. It was possible to create a simple, fast and cost-effective method to obtain an overview whether nanoparticles are included in a cosmetic product or not.

Influence of drug content, type of semi-solid vehicle and rheological properties on the skin penetration of the model drug fludrocortisone acetate.

Throughout Europe, topical creams containing corticosteroids are diluted with various neutral cream bases to meet the specific needs of patients. Even though this practice has been common for years, its effect has not been thoroughly investigated and so the effectiveness of the diluted topical steroidal creams is difficult to predict. In the present study, the model drug fludrocortisone acetate was incorporated into three cream bases of different hydrophilicity that are commonly used in Austria. Different final drug concentrations were chosen for comparative studies. Additionally, a semi-solid preparation developed by our group was investigated for comparison. These formulations were tested in diffusion and tape stripping experiments. Diffusion cell studies showed that changes in drug concentration do not necessarily change the skin permeation behaviour in vitro. The tape stripping protocol was successfully optimised for investigation of semi-solid preparations to provide reproducible and accurate results despite the challenges of investigating semi-solid formulations. The results showed that tape stripping experiments are more suitable to elucidate subtle differences between formulations. The composition of the cream bases exhibited stronger effects on the skin penetration of the steroidal drug irrespective of its concentration than the rheological properties. No correlation between formulation viscosity and skin penetration was found.