In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type multiple emulsions via dielectric spectroscopy.

Multiple emulsions offer various applications in a wide range of fields such as pharmaceutical, cosmetics and food technology. Two features are known to yield a great influence on multiple emulsion quality and utility as encapsulation efficiency and prolonged stability. To achieve a prolonged stability, the production of the emulsions has to be observed and controlled, preferably in line. In line measurements provide available parameters in a short time frame without the need for the sample to be removed from the process stream, thereby enabling continuous process control. In this study, information about the physical state of multiple emulsions obtained from dielectric spectroscopy (DS) is evaluated for this purpose. Results from dielectric measurements performed in line during the production cycle are compared to theoretically expected results and to well established off line measurements. Thus, a first step to include the production of multiple emulsions into the process analytical technology (PAT) guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be beneficial in determining the crucial stopping criterion, which is essential in the production of multiple emulsions. The stopping of the process at a less-than-ideal point can severely lower the encapsulation efficiency and the stability, thereby lowering the quality of the emulsion. DS is also expected to provide further information about the multiple emulsion like encapsulation efficiency.

Evaluation and quantification of spectral information in tissue by confocal microscopy.

A confocal imaging and image processing scheme is introduced to visualize and evaluate the spatial distribution of spectral information in tissue. The image data are recorded using a confocal laser-scanning microscope equipped with a detection unit that provides high spectral resolution. The processing scheme is based on spectral data, is less error-prone than intensity-based visualization and evaluation methods, and provides quantitative information on the composition of the sample. The method is tested and validated in the context of the development of dermal drug delivery systems, introducing a quantitative uptake indicator to compare the performances of different delivery systems is introduced. A drug penetration study was performed in vitro. The results show that the method is able to detect, visualize and measure spectral information in tissue. In the penetration study, uptake efficiencies of different experiment setups could be discriminated and quantitatively described. The developed uptake indicator is a step towards a quantitative assessment and, in a more general view apart from pharmaceutical research, provides valuable information on tissue composition. It can potentially be used for clinical in vitro and in vivo applications.

Feasibility of Monte Carlo simulations in quantitative tissue imaging.

PURPOSE: The feasibility of Monte Carlo simulations as a tool to facilitate quantitative image analysis is investigated by means of simulating light transport in skin phantoms. METHODS: A Monte Carlo tool is used to compare if simulated fluorescent signals show agreement with measured data. The lipophilic fluorescent probe Nile Red and dedicated skin phantoms are also used in simulations to investigate the influence of the optical properties of the skin on the signal. RESULTS: It is shown that the simulated and measured fluorescence signals show linear behavior up to a certain concentration of Nile Red. The simulations of the skin phantoms show the varying influence of single skin layers on the fluorescence signal. A calibration factor for quantitative analysis can be determined for the different skin layers. CONCLUSION: Characterizing the influence of different media on imaging signals is a primary task in developing quantitative analysis methods. Monte Carlo simulations are a useful tool to investigate imaging properties of biological specimen where quantifying signals is important. However, detailed models must be provided.