As if it isn’t hard enough to develop the perfect formula in the laboratory, successfully scaling a bench formulation to production sizes creates further challenges. A product’s successful scale-up will consistently offer the consumer the intended benefits while providing a profitable return for the manufacturer. Therefore, it is critical that the aesthetics created in the laboratory are replicated in a range of larger vessels in production facilities. Many variables play a role in making this possible, but by following certain steps and guidelines, product developers can move to the production stage confidently. The more experience formulators have in scaling-up batches, the more knowledge they can bring back into their laboratories to ensure successful transitions to production.
The general question formulators must ask themselves is whether a process is optimal or just functional. Although formulators are pulled in many directions, it is beneficial to try to optimize products before they are being produced on a larger scale. A good practice is to invite engineers or production compounders to view a batch being made on the lab bench because observing the manner in which the formulator adds sequences and mixes the product can offer insights to production processing—and possibly catch any issues early enough to be modified.
A good process engineering group will challenge the formulator with questions ranging from sequencing, mixing speeds, homogenization energy and salt curves, to cooling rates. Whether the formulator is developing skin care, hair care or makeup products, the principal concepts from a formulator’s standpoint as well as a process engineer’s standpoint will be reviewed here in addition to guidelines that are needed to ensure consistent successful production batches.
Recognizing the key ingredients in the formula is a good start. Choosing emulsifiers carefully will yield a narrow droplet size distribution and stable product without using energy to hold the formula together.
Mixing speeds and the amount of energy introduced during processing have a direct impact on the final aesthetics, stability and homogeneity of the final product. The addition of high shear mixing in the laboratory will ensure that the oil droplets formed in the emulsion become properly distributed throughout the external water phase.1 While high shear mixing or homogenization may be an easy way to stabilize a lab batch, this will not always translate to a stable emulsion over time and in production. If it takes a prolonged period of high speed homogenization to ensure an emulsion is stable in the laboratory, the product may not be as stable as it should be. A borderline-stable formula in the lab may lead to issues in production such as batch separation, emulsion bleeds, and drops or variations in viscosity. Borderline-stable formulas are also sensitive to filling and shipping, so emphasis must be placed on developing a formula that can be scaled-up. It is also helpful to measure and record the speed of a propeller or sweep mixing using a tachometer and to be aware of the RPMs used on the lab homogenizer. To make production efficient, confirm the equipment and the speed used to put the product together by trying different scenarios.
Proper mixing will also depend on the ability of the batch to circulate and continuously pass through the homogenizer with the help of sweep, propeller and bottom to top recirculation. This may be easy for a small lab batch but can be more complicated in production, especially if the product is viscous. The flow rate and the path the product goes through will affect the shear rate being developed. As the batch cools and thickens, more energy may be required to maintain sufficient batch turnover and ensure all particles see the homogenizer. In addition, making sure that the batch can withstand mixing and flow at the different temperatures throughout the process will make certain the product is homogeneous. This will allow uniform droplet size and consistent cooling.2
Heating and Cooling
It is also important to understand the heating and cooling parameters required to make a formula. By knowing the ingredients’ melting points and the temperature needed to dissolve them in the different phases, an exact temperature can be identified for the emulsion to take place. In liposome technology for instance, maintaining the temperature of the oil and water phases as they are transferred together yields consistent liposome size.3
Cooling is just as important as heating. A common problem seen with uneven cooling would be, for example, the premature solidification of waxes in the development of an emulsion. Lab batches can cool to ambient temperature rather quickly, but it takes much longer for a plant to cool down a productionsize batch. It is recommended that formulators challenge the formula with shear testing to see if extended mixing during cool down adversely affects the viscosity, as cooling capabilities may vary.
Further, manufacturing plants typically cool the mixing kettles using city water that can vary in temperature depending on the season and plant location. So a plant in Minnesota will be able to cool a product much more quickly in December than in July. When batching in the laboratory, use a cooling rate that can be reproduced in the plant; air cooling would be preferred to ice baths to ensure the temperature is lowered at a gradient reproducible in the plant. Formulators are also challenged with using homogenizers that transfer heat energy to the product, which sometimes requires additional cooling at critical steps. In general, the systematic cooling of the entire batch is essential to the product’s stability. Ensuring that the product’s flow and movement is even throughout the kettle will provide even cooling throughout the emulsion.
Another way to optimize a formula and process is via sub-phases. Subphases or pre-mixes are smaller phases comprised of several ingredients that require pre-mixing to dissolve, wet or react prior to their addition to the main phase. For example, certain gum thickeners hydrate better in glycerin solutions rather than water, which could cause lumping in the finished product. Therefore, these few ingredients can be added in an appropriately sized vessel and pre-mixed with propeller agitation until the powder is completely wetted and then added to the main phase. While some sub-phases may be critical to the aesthetics or chemistry of the formula, other sub-phases created on the bench might not be necessary. Combining sub-phases can benefit the manufacturer by saving time and money in the plant since some facilities may not have the capacity or capability to easily create sub-phases.
Adding components to the main phase should be attempted before submitting a request that the engineer set up an auxiliary vessel merely because the process had never been done in that way. If sub-phases are necessary, however, ensure that this type of mixing is possible for production. Also, consider if a sub-phase could be mixed with just a propeller mixer rather than a homogenizer.
Rate and Order of Addition
The rate and sequence for transferring materials into the main kettle must also be controlled and consistent. Each phase should have adequate mixing time before the subsequent sequence is added, and phases and materials that could potentially be reactive should be added in sequences that are spread apart and have time to mix in the batch to avoid reactions. This is commonly seen with pH adjusters, high salt-contributing actives and various thickeners. The importance of the rate of addition can be seen in w/s emulsions, where the water is slowly added under low shear agitation. This ensures that the hydrophilic site and hydrophobic backbones of the silicone polymers have time to orient themselves in the water phase, developing proper w/s droplets. Adding water too quickly causes the droplets to coalesce over time, causing viscosity to drop and phases to separate. To maintain uniform mixing, the order and rate of addition during a scale-up may be modified. Formulators may find that the batch cannot withstand over-mixing during a long addition sequence.
Toward the end of a formulation process, adjustments are typical, whether for color, pH or viscosity. These adjustments ensure consistency in aesthetics as well as micro integrity. If in-process adjustments are necessary, determining the specific amount of adjuster added is useful so that in the future, it can be added up front during lab batches and pilots to optimize the process for production. For surfactant-based products, where the amount of salt in certain ingredients can vary from lot to lot, making lab batches with multiple lots can provide insight on the amount required for the pH or viscosity adjustment; it is easier to slightly adjust the pH or viscosity of a batch near the end of the process rather than to initiate prolonged mixing with a long adjustment sequence after the batch has been completed.
To optimize a formula for scale-up and production, it is important to understand it inside and out. When formulating, think about the order of addition and why ingredients are added at certain times during the process. Various actives, preservatives and fragrances degrade or change characteristics if they are added at high temperatures. In the case of powder ingredients, some are easily dispersed or dissolved into the batch at a certain temperature while others take extended mixing. In many instances, powders need to be wetted beforehand to avoid prolonged mixing and aeration. For scrub products, consider whether it is possible to add the beads at a higher temperature during cooling so they can be incorporated when the product is less viscous. Understanding the ingredients and their limits will equate to a robust product in production. The guidelines presented in this article are just some of the things to consider when formulating in the laboratory. It is important to think through them at the beginning of the formula development process to ensure the product developed in the laboratory can be replicated on a larger scale. Most importantly, open communication with the process engineer and a thorough understanding of the formula will guarantee a product that is reproducible both in the lab and in production.
1. D Buell, K Barclay, P Block, D Crissien, J Junker, J Rotando, B Victor and D Yacko, The Manufacture of Cosmetics, Harry’s Cosmeticology, Chemical Publishing Co., Revere, MA, pp 788–749
2. JY OldShue, Liquid-Liquid Emulstions, pp 125–140, and Scaleup, pp 192–215, Fluid Mixing Technology, McGraw-Hill, New York (1983)
3. H Hayashi, K Kono and T Takagishi, Temperature Dependent Associating Properties of Liposomes Modified with a thermo sensitive polymer, Bioconjug Chem 9 (3) 382–389 (May–Jun 1998)