J. Soc. Cosmetic Chemists, 17, 135-147 (1966) Product Stability' Prognostication, Placement, Parameters Part I L LO YD KENNON, Ph.D.* Presented before the Eleventh Annual Seminar, September 14-15, 1965, Los Angeles Synopsis--Chemical kinetics provides the basic principles which can help study of the deterioration of pharmaceutical and cosmetic products. Principles of kinetics, which could be used to predict long-term stability of finished formulations, are reviewed, and techniques are described which can be used in programming stability studies. Finally, those properties of emulsions, suspensions, and solids are discussed which are amenable to measurement and can be used as parameters for establishing and predicting deterioration of finished consumer products. INTRODUCTION To tsegin a discussion of a topic such as product stability and chemical kinetics, it probably would be fitting to start with several appropriate quotes from the Old Testament, or failing this, we might record some of the musings of such all-time-greats as Aristotle or Archi- medes. Probably most effective, however, would be to have found a log-log plot on a bas relief in the Egyptian pyramids. Upon such a foundation one then could build a chronological historical outline which would connect the work of antiquity with that of today. However, except for one brief bow to tradition, we will dispense with the historical approach. This brief lapse entails mentioning the observation, prob- ably not his alone, of Heraclitus (Heradeitos of Ephesos), who in about 500 B.C. said "panta rhei," or, all is flux, everything flows. Certainly, * Research and Development Laboratories, Bristol-Myers PrGducts, Hillside, N.J. 07207. 135

136 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS this fact is one which appears to be relatively immutable. Possibly this Ionian Greek philosopher was stimulated to make this observation be- cause he was living in a time in which fire was thought to be one of the (if not the) primordial substances we too have, of course, observed that a flame, being such a changeable thing, may well be a symbol (possibly a clue?) that all things are subject to a general and ceaseless process of alteration. Regardless, Heraclitus stressed the constancy of change, and here we wish to discuss change as it affects the products we create. PROGNOSTICATION The purpose of this section will be to review basic, classical chemical kinetics, to indicate the rationale behind choosing certain of the pertinent principles from this segment of physical chemistry, and to demonstrate how these new tools may be used. For our purposes, the basic aim is to learn how to follow reaction rates in an efficient and orderly manner, i.e., in a way that makes pos- sible prediction of the future behavior of the system being observed. By reaction rate we mean the rate of degradation of a material. We will equate the degradation of a material to the disappearance or lowering with time of the concentration of a component of the formulation under observation. Basically, we can review the possible happenings by con- sidering two concepts: molecularity and order. Consider first the molecularity of reactions. A unimolecular reaction is one in which only one molecule takes part, as in, e.g., a dissociation or rearrangement. In a bimolecular reaction two molecules are involved, and collision of the two is needed. Most of the familiar reactions of formation would fall into this class. A termolecular interaction in which three molecules are involved in simultaneous collision is rare and is not unlike the problems acknowledged by the familiar "three is a crowd" adage. For practical purposes, molecularity is most easily interpre- table, i.e., east into useful form, by observing experimentally how a rate of reaction or degradation is influenced by the concentrations of the react- ing or degrading materials, regardless of how the actual happenings are taking place on a molecular scale. The next concept needed then is that of reaction order definitions follow: First Order. The rate is directly proportional to the concentration of the material reacting. Mathematical treatment yields an equation describing this situation: