Formulation Chemistry

David Young
Cytoclonal Pharmaceutics Inc.

Formulation chemistry is one of the disparities in the chemistry industry. There are many jobs, but extremely few degree programs that adequately train students for a formulation position. As a result, most formulation chemists are either self taught or have in essence been apprenticed under experienced researchers.

Simply put formulation is the mixing of compounds which do not react in order to get a mixture with the desired characteristics. Examples of formulations are adhesives, paints, inks, cosmetics, detergents and many pharmaceutical products. This is product development work that is very focused on the characteristics needed for a product to be profitable.

Since no reactions are being done, there is no reason to work with gram formula weights of compounds. Most formulations are done by measuring liquids by volume and solids by weight. A product may go to market without any chemical equations ever being written down.

The chemical principles involved

Even though there are no chemical reactions involved, there are many aspects of chemistry present in a formulation. Some of the chemistry involved is thermodynamics of mixing, phase equilibria, solutions, surface chemistry, colloids, emulsions and suspensions. Even more important is how these principles are connected to adhesion, weather resistance, texture, shelf life, biodegradability, allergenic response and many other properties.

Quite a bit has been done by a fairly trial and error method. In this scheme, the product development chemist will have a list of substances used to modify mixtures (i.e. thickeners). They will then go through a trial and error process to see what concentration of which compound will work best for a specific application. Of course, the scientists and engineers hired to do this work recognize the value of having an understanding of the processes involved to guide their choices of which to try. In product design more than many other areas, new researchers are hired with very basic knowledge and trained internally to understand formulations. In recent years, there has been an increase in work to develop the underlying scientific principles, and apply them in the form of software to predict formulations. At the present time, some parts of the field are following this approach, while other parts of the field are still using a trial and error scheme.

Where should formulation chemistry fit in the curriculum? A lecture discussion might fit in with either general chemistry or physical chemistry. A laboratory experiment could be included at almost any level, but perhaps freshman is best. Unfortunately, formulations do not make a particularly good graduate research project. The natural collaboration and funding source for a formulation project would be working with an industrial partner. However, the product development stage is one at which industries are most sensitive about keeping their knowledge safely in house. Industries tend to work with academic partners on developing new technology but are very hesitant to share their profitable trade secrets with academic researchers. When collaborations are made, the industry will naturally put strict restrictions on publishing the results (other than in a patent held by them). Since academic researchers base their success on the number of publications rather than on profits this is an unfavorable arrangement for the academic researchers as well.

The following sections give an idea of the concerns addressed by formulation chemists in a number of areas. There are many other areas in which formulations are important. See the references for more research areas.

Adhesives

Most adhesives are a mixture of a bonding agent and a solvent, which seep into minute cracks and harden as the solvent evaporates. A few adhesives, such as super glue and epoxy actually undergo a chemical reaction as they harden. Silicon based adhesives are used for high temperature applications such as car muffler repair.

Paints

The components of a paint are a base pigment, a mixture of compounds to give it a particular color, a binder and a solvent which will evaporate to give a solid surface. An additional pigment may be added to give a glossy appearance. Some of the classes of paints are water based, latex, oil, acyrlic and epoxy based. House paints are formulated for a balance of durability and reasonable cost. More expensive high durability paints are used for automobile and aircraft bodies.

Inks

Distinctly different market forces drive the development of different types of ink. The ink used for newsprint, such as newspapers or paperback novels, must be cheap and have the consistency of a thick sludge to properly feed through the ink rollers of a printing press. True color quality is important for glossy magazines. Flow characteristics are important for pens and computer printers. The formulation of a good copy machine or laser printer toner depends upon its electrostatic properties.

Cosmetics

A number of advances in cosmetics have been made in recent years. The primary changes are in non-allergenic formulations and longer duration wearability. This is a very competitive market in which a particular look, marketing or convenient application can sometimes make a product more profitable than other factors.

Detergents

Detergents are a type of surfactant in that they change the surface tension of the solution. Recent advances in laundry detergents include bleach substitutes and the addition of enzymes. An ideal enzyme is one which efficiently breaks down the organic matter that some stains are made of while hopefully doing minimal damage to the organic matter which the clothes are made of. Dish washing detergents are formulated to effectively clean without damaging the skin of the person doing dishes. Another important area is industrial detergents which may have far more powerful ingredients tailored to a particular production process.

Pharmaceuticals

The pharmaceutical industry is one of the few in which there are excellent formulation courses taught in universities. The formulation aspect of pharmaceuticals pertains to drug delivery. The usefulness of a drug is based not only on its effectiveness in treating a condition but also on how readily it can be administered to the patient. The ideal drug is in tablet form and bland tasting. Tablets are formulated with additional ingredients to prevent stomach upset, give a timed release and hold the tablet together as a solid. Liquid medications must often be mixed with strong flavorings or alcohol to hide the taste of the medicine.

References

An excellent introduction to the individual application areas is
"Kirk-Othemer Encyclopedia of Chemical Technology" J. I. Kroschwitz, M. Howe-Grant Eds., John Wiley & Sons (1996)
See the articles on Adhesives, Aerosols, Asphalt, Building Materials, Cement, Coatings, Colloids, Colorants, Composite Materials, Controlled Release Technology, cosmetics, Defoamers, Detergency, Dental Materials, Dispersants, Drug Delivery Systems, Dyes, Emulsions, Enamels, Epoxy Resins, Explosives & Propellants, Fillers, Film & Sheeting Materials, Flavors & Spices, Flocculating Agents, Foams, Gelatin, Gums, Hair Preparations, Inks, Latex Technology, Metallic Coatings, Paint, Paper, Perfumes, Pigments, Polishes, Refractory coatings, Release Agents, Repellents, Roofing Materials, Sealants, Soap, Sol-Gel Technology, Sprays, Solders & Brazing Alloys, Solvents, Surfactants, Tar & Pitch and Waterproofing.

Documents on the web on industrial organic chemistry are at
http://c.chem.ualberta.ca/~plambeck/che/struct/s0909.htm

Documents on the web pertaining to drug formulation are
http://www.clinmark.com/drug-formulation.html
http://w3.ouhsc.edu/bsmith/Drug_Delivery_Systems_I/PHAR%207614%20Syllabus.html.html

Many of the fundamental principles come from physical chemistry. A good starting point is the sections on solutions, phase equilibrium, surface chemistry and solids & liquids in
I. N. Levine "Physical Chemistry" McGraw-Hill (1995)

A compilation of techniques for predicting chemical properties is
W. J. Lyman "Handbook of Chemical Property Estimation Methods" McGraw-Hill (1982)

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