Optimizing Vaccine Adjuvant Filtration - The viscosity of oily emulsions can reduce filter capacity and bacterial retention. - BioPharm International


Optimizing Vaccine Adjuvant Filtration
The viscosity of oily emulsions can reduce filter capacity and bacterial retention.

BioPharm International Supplements

Mechanisms That Affect Capacity and Retention

Figure 1. Relative capacity of a symmetric and an asymmetric membrane for a model oil-in-water emulsion. The asymmetric membrane has a much higher capacity in this stream, which can be attributed to higher intial flux.
Using an oil-in-water emulsion as our model stream, the study team investigated the mechanisms that affect capacity and retention. Throughput of a membrane in a typical filtration application is affected by many factors, including membrane structure, the viscosity of the suspension, particle size, particle concentration, and filter train resistance. The filter's overall throughput is determined by flux and capacity. Flux is determined by driving forces (e.g., inlet pressure), stream properties (viscosity), and the membrane structure (i.e., pore size, asymmetry). Capacity is also driven by the membrane structure and by properties of the process stream, such as particle load.

Figure 2. Viscosity of the model stream as a function of temperature. As expected, the suspension is less viscous at higher temperatures, but at all temperatures, its viscosity is higher than that of water, which is 0.01 poise at room temperature.
The impact of membrane structure on capacity was demonstrated by comparing two membrane structures that varied in asymmetry. As Figure 1 shows, the more asymmetric structure had a higher capacity, which we believe was associated with higher initial flux. Regardless of membrane structure, the flow rate was very low, even early in the filtration process. The viscosity of the model emulsion was one of the factors that contributed to the observed throughput. As Figure 2 shows, the viscosity of the emulsion is high compared to that of water. As a result, the flux of the emulsion is lower than the flux of a typical aqueous stream. The reduced flux significantly affects processing time and filter sizing.

Figure 3. Relative capacity increases as average particle size decreases.
Testing was done to observe the plugging behavior of membranes when filtering the emulsion. In addition to the low initial flux, the flow declined rapidly after the filtration started, suggesting that the membranes were plugging quickly. To investigate the impact of the model stream on membrane plugging, we manipulated the size and concentration of particles in the model stream. Smaller particles increased capacity, as shown in Figure 3. This is an indication that particle plugging is also an important factor in filter capacity.

To confirm that pore blockage was the mechanism of membrane plugging, we used common fouling models to fit our data. Fouling models use approximations of how a filter plugs to fit the fouling curves (volume versus time). Typical fouling models include caking (the build-up of particles on the filter surface), complete pore blockage (blocking of a pore opening by a single particle), and gradual pore plugging (build up of particles within a pore to gradually restrict flow).3 By plotting our data using the standard fouling models, we found that the classic Vmax model,4,5 which is based on gradual pore plugging, best fit the data, and accurately predicted the plugging performance and overall capacity. This analysis provided further evidence that pore blockage was the primary mechanism of flow decay.

Figure 4. Dependence of capacity on pressure. Capacity increases with increasing pressure. The same membrane was challenged, in duplicate, at constant pressures of 5, 7.5, 10, 15, 20, and 30 psi. Capacity was determined as the volume at which the flow had declined to 10% of its initial value in the emulsion.
Although our testing showed that the classic Vmax model predicted the flow decay behavior, we also found that the plugging behavior was pressure-dependent. Capacity increased with increasing pressure drop across the membrane, in some cases disproportionately to the increase in pressure. Figure 4 shows the impact of pressure on filter capacity, which was non-linear. A number of factors may contribute to this behavior, one of which is suspected to be the high viscosity of the emulsion compared to a typical aqueous stream. Several follow-up experiments confirmed this theory.

blog comments powered by Disqus



Bristol-Myers Squibb and Five Prime Therapeutics Collaborate on Development of Immunomodulator
November 26, 2014
Merck Enters into Licensing Agreement with NewLink for Investigational Ebola Vaccine
November 25, 2014
FDA Extends Review of Novartis' Investigational Compound for Multiple Myeloma
November 25, 2014
AstraZeneca Expands Biologics Manufacturing in Maryland
November 25, 2014
GSK Leads Big Pharma in Making Its Medicines Accessible
November 24, 2014
Author Guidelines
Source: BioPharm International Supplements,
Click here