Dynamic Light Scattering of Biopharmaceutics-Can Analytical Performance Be Enhanced by Laser Power?

BACKGROUND: Dynamic light scattering (DLS) is an important tool to characterize colloidal systems and adequate sizing is particularly critical in the field of protein formulations. Among the different factors that can influence the measurement result, the effect of laser power has so far not been studied thoroughly. METHODS: The sensitivity of a DLS instrument was first considered on a theoretical level, followed by experiments using DLS instruments, equipped with two different lasers of (nominal) 45 mW, and 100 mW, respectively. This work analyzes dilute colloidal dispersions of lysozyme as model protein. RESULTS: Theoretical findings agreed with experiments in that only enhanced laser power of 100 mW laser allowed measuring a 0.1 mg/mL protein dispersion in a reliable manner. Results confirmed the usefulness of the presented theoretical considerations in improving a general understanding of the limiting factors in DLS. CONCLUSIONS: Laser power is a critical aspect regarding adequate colloidal analysis by DLS. Practical guidance is provided to help scientists specifically with measuring dilute samples to choose both an optimal instrument configuration as well as a robust experimental procedure.

Introducing diffusing wave spectroscopy as a process analytical tool for pharmaceutical emulsion manufacturing.

Emulsions are widely used for pharmaceutical, food, and cosmetic applications. To guarantee that their critical quality attributes meet specifications, it is desirable to monitor the emulsion manufacturing process. However, finding of a suitable process analyzer has so far remained challenging. This article introduces diffusing wave spectroscopy (DWS) as an at-line technique to follow the manufacturing process of a model oil-in-water pharmaceutical emulsion containing xanthan gum. The DWS results were complemented with mechanical rheology, microscopy analysis, and stability tests. DWS is an advanced light scattering technique that assesses the microrheology and in general provides information on the dynamics and statics of dispersions. The obtained microrheology results showed good agreement with those obtained with bulk rheology. Although no notable changes in the rheological behavior of the model emulsions were observed during homogenization, the intensity correlation function provided qualitative information on the evolution of the emulsion dynamics. These data together with static measurements of the transport mean free path (l*) correlated very well with the changes in droplet size distribution occurring during the emulsion homogenization. This study shows that DWS is a promising process analytical technology tool for development and manufacturing of pharmaceutical emulsions.

Introduction of diffusing wave spectroscopy to study self-emulsifying drug delivery systems with respect to liquid filling of capsules.

The rheology of self-emulsifying drug delivery systems (SEDDS) is not thoroughly characterized these days. Since mechanical rheometers are often not well suited to study this kind of systems, there is need for novel physical methods. Several new optical techniques based on microrheology have recently made significant progress. We apply for the first time a specific microrheological technique called diffusing wave spectroscopy (DWS) to study different SEDDS. The obtained data were then correlated with the dosing precision of automated capsule filling. As a result, the dynamic viscosities obtained from microrheology were in accordance with data from capillary viscosimetry. The DWS measurements revealed that all formulations had a clearly measurable storage modulus at frequencies >200 rad/s. Thus, all samples were low-viscous, while exhibiting non-Newtonian flow behavior. Obtained values of storage and loss modulus were then successfully correlated with the weight variability of capsules that were filled on a machine. In conclusion, the DWS technique enabled rheological analysis of self-emulsifying systems in a broad frequency range. The good data correlation with a capsule quality attribute was especially promising, since microrheological techniques are typically contact-free. Thus, they have a high potential in a quality by design framework of formulation development and production.

Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates.

The nonhuman primate model is suitable to study mechanisms of functional recovery following lesion of the cerebral cortex (motor cortex), on which therapeutic strategies can be tested. To interpret behavioral data (time course and extent of functional recovery), it is crucial to monitor the properties of the experimental cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5 weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood flow) and anatomical assessment with magnetic resonance imaging (T2-weighted MRI). The cerebral blood flow, measured online during subsequent injections of the ibotenic acid in the motor cortex, exhibited a dramatic increase, still present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the cerebral blood flow was strongly reduced (below reference level) and the hypersignal disappeared from the MRI scan, although the lesion was permanent as histologically assessed post-mortem. The MRI data were similar in the second monkey. Our experiments suggest that LSI and MRI, although they reflect different features, vary in parallel during a few weeks following an excitotoxic cortical lesion.