A Colloid Stability Analyzer for the Analysis of Stability of Complex Formulations

Scientists in the biotechnology, pharmaceutical, health-care, food and beverage, chemical and petrochemical, polymer, and other industries have spent considerable time studying the relationship between the properties of a material and its acoustical characteristics. To achieve that, for decades they have used a wide range of ultrasonic techniques for nondestructive testing and imaging. Ultrasound as an analytical tool has revolutionized diagnostics in medicine, but the application of this method to materials analysis has historically been held back because of problems such as ultrasonic design, electronics and size of sample handling, complicated measuring procedures, and resolution. Recent advances in computing power and digital techniques, however, have made it possible to design versatile laboratory instruments utilizing high-resolution ultrasonic spectroscopy (HR-US) for applications ranging from ceramics to polymer science to cell biology and emulsions.

High-resolution ultrasonic spectroscopy

High-resolution ultrasonic spectroscopy is a novel technique for nondestructive materials analysis based on the precision measurements of highfrequency sound waves, similar or higher to those used by dolphins for communication and bats for navigation. These waves, unlike their light counterparts, propagate through most materials, including opaque samples, and allow direct probing of intermolecular forces. Compression and decompression of the ultrasonic wave cause oscillation of molecular arrangements in the sample, which responds by intermolecular attraction or repulsion.

The amplitudes of deformations in the ultrasonic waves employed in analytical ultrasound are extremely small, making ultrasonic analysis a nondestructive technique. Another advantage is that it is relatively easy to change the wavelength of the ultrasonic wave. Unlike optical techniques, in which the wave originates in a light source and therefore requires special effort to obtain a needed spectral purity, ultrasonic waves are synthesized electronically. Therefore, a typical ultrasonic spectrometer can cover a broad range of wavelengths.

New analytical capabilities for research, product development, quality, and process control are provided in the HR-US ultrasonic spectrometers from Ultrasonic Scientific Ltd. (Dublin, Ireland). Applications include analysis of chemical reactions, conformational or phase transitions in polymers and biopolymers, aggregation and gelation processes, particle sizing, stability of emulsions and suspensions, formation of micelles and critical micelle concentration (CMC) measurements, ligand binding, and composition analysis. The Colloid Stability Analyser (Ultrasonic Scientific) is an HR-US instrument that provides precise quantitative measurements, allowing accurate information to be gathered on average particle size, particle concentration, and rate of sedimentation/creaming and assessing the degree of flocculation/aggregation in suspensions. In addition, the instrument enables the analysis of opaque materials and provides data processing algorithms. The analyzer does not require the dilution of samples yet provides information related to bulk properties. Inverted gravity measurement is also possible, as are on-line flow measurement applications.

Application of analyzer

Aggregation/sedimentation of solid polymeric particles

Phase separation and stabilization can occur in a diverse range of colloidal-type systems, ranging from those of cell biology to large industrial chemical operations. Due to the high degree of attention focused on such applications, there is a high demand to analyze such systems accurately. Since colloids are materials with complex microscopic particles (or large molecules) embedded in a liquid or gas, traditional techniques such as microscopy, light scattering, turbidity, and rheology have been used to assess stability and microstructures.

The above techniques have limitations, and systems information has previously been unobtainable; these limitations can be overcome with the Colloid Stability Analyser. Microscopy, for example, provides mostly qualitative information and is prone to human error. It is difficult to perform analyses in real time, and often complex sample preparation is required. Because HR-US utilizes computing power and digital techniques, the potential for human error is removed and sample preparation is simple. Light scattering in the bulk sample requires dilution and optical transparency, neither of which is necessary for HR-US, and has limited capabilities in concentrated samples. Turbidity is restricted by the optical density of the sample and has problems with quantitative microstructural information, including aggregation extensions and particle size. HR-US is completely nondestructive, and provides quantitative information on a variety of attributes via data processing algorithms, including aggregation extension and particle size.

Figure 1 - Aggregation and sedimentation processes of polymer particles.

Figure 1 demonstrates a typical scenario of aggregation and sedimentation in a polymer suspension. The inset illustrates an aggregation, which can occur after the initial starting point of particles being evenly distributed throughout the solution. Figure 2 is a HR-US kinetics depiction of differential relative velocity (m/s) and relative attenuation (1/m) illustrating HR-US velocity and attenuation of polymer aggregated sedimentation. It shows the suspension of polystyrene particles in aqueous solution at 25 °C. Results are achieved at three different frequencies: 7 MHz, 12 MHz, and 15 MHz. In this system, there is a decrease in velocity and attenuation at all frequencies, indicating sedimentation and particle aggregation processes.

Figure 2 - HR-US velocity and attenuation analysis of polymer aggregation and sedimentation.

Creaming, whereby particles rise to the top of a suspension, is a process that occurs in many applications; the HR-US Colloid Stability Analyser can be used here to provide information. Figure 3 displays a generic creaming process for a system containing different particle sizes. Examples include the movement of fat globules to the top of milk, and the creaming of drug formulations.

Figure 3 - Creaming process for a system containing different particle sizes.

Particle size analysis software

Along with the Colloid Stability Analyser, is the HR-US Particle Size Analyser (Ultrasonic Scientific), a powerful piece of software that is capable of providing predictions and real-time analysis of parameters such as particle size and particle processes. The example provided in Figure 4 illustrates the sedimentation profile of polystyrene particles in suspension obtained from ultrasonic profiles using this software.

Figure 4 - Sedimentation profile in a suspension of polystyrene polymer particles determined by the HR-US particle size analyzer.

Conclusion

The Colloid Stability Analyser offers many opportunities for the improved analysis of nondestructive materials. The analyzer can be pressurized up to 10 bar, allowing the analysis of liquids with low boiling points and liquids at high temperatures (above boiling point). It features a temperature range between –20 °C and 120 °C, and can perform nondestructive and small sample analyses at concentrations as low as 0.3 ppm. The technology facilitates the use of 1-mL cells for parallel/differential analysis, a frequency range of 2.5–15 MHz, absolute temperature control to 0.01 °C, and resolution to 10–5% for velocity and 0.2% for attenuation measurements.

Ms. O’Driscoll is with Ultrasonic Scientific Ltd., 1 Richview Office Park, Clonskeagh, Dublin 14, Ireland; tel.: +353 1 218 0600; fax: +353 1 218 0601; e-mail: [email protected]. Dr. Buckin is with the Dept. of Chemistry, University College Dublin, Belfield, Figure 4 Sedimentation profile in a suspension of polystyrene polymer particles Dublin, Ireland.

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