552 JOURNAL OF COSMETIC SCIENCE THE ROLE OF SURFACE ACTIVE, ACTIVE INGREDIENTS ON CREAM STABILITY Introduction Lorraine E. Pena, Ph.D. and Pamela J. Secreast Pfizer Pharmaceutical Sciences Research Formulations Emulsion stability is dependent upon formation of a close-packed interfacial film composed of fally amphiphiles. However, this is an overly simplistic view of the interfacial interactions and only accounts for a fraction of the fatty amphiphile composition of the emulsion. The gel network theory provides a more complex view. According to this theory, a gel network forms from interpenetration of the emulsifier into the fatty amphiphile (1). This comprises the balance of the formulation fatty amphipbile. Emulsion consistency is defined by the extent and integrity of the gel network. Emulsions based on nonionic emulsifiers develop consistency at a slower rate than those based on anionic emulsifiers. This is attributable to slower diffusion of the larger polymeric nonionic emulsifier into the fatty amphiphile. Some surface-active, active ingredients (e.g. drugs and preservatives) are known to adversely affect emulsion stability. Their impact on stability increases wilh concentration. Instability is manifested by conversion to a tllinner cream or lotion, development of a stringy, elastic consistency and formation of a highly pearlescent appearance. The consistency development and destabilization process of a model cream containing a surface-active drug was previously presented (2). The active ingredient, TEA-ibuprofen, being highly surface active, was identified as the primary factor in the phase separation and delayed viscosity development of the cream tormulations. The mechanism by which Lhis surface-active, active ingredient destabilizes the model cream is the subject of this study. Experimental An objective of the study was to find a suitable surfactant with a lower surface tension and stronger interfacial activity than TEA-ibuprofen. The surfactants to be tested were chosen based on the following criteria: supplier literature indicating low surface tension, water solubility, structural similarities or different functional groups. Different counterions for the ibuprofen salt were also tested. A Fisher Autotensiomat Model 215 employing the duNouy ring detachment method was used. All measuremenL'i were performed at room temperature. Resulu Two important pieces of information can be obtained using the duNouy ring detachment method: 1) the surface tension y above tl1e critical micelle concentration and 2) an indication of the tensile strength of the interfacial film, which is related to surface viscosity. These two parameters became the target of the investigation. Most solvents and surfactant solutions undergo only a slight deformation of the meniscus before breaking. However, the TEA-ibuprofen solution exhibits an extraordinary amount of deformation and resiliency and a gradual necking-off of the meniscus prior to breaking. This resiliency is suspected to be related to the surface viscosity and elasticity. The resiliency of tl1e 5% TEA-ibuprofen solution meniscus appears in the autotensiomat recording as a post-peak tailing that has been termed the "relative tensile strength". Figure la illustrates the post-peak tailing. The recording for water in Figure lh shows a typical surface tension measurement associated with solutions having low surface viscosities. The 5% TEA­ ibuprofen aqueous solution had a surface tension 'Y of 31.5 dynes/cm at the peak of the curve and a relative tensile strength of 48 chart divisions. 111e experiments were performed in three phases: 1) nonionic surfactants were tested as aqueous solutions and in combination with 5% TEA-ibuprofen to find an emulsifier with a lower surface tension to overcome the dominance of TEA-ibuprofen at the interface, 2) solutions of anionic surfactants were tested in order to observe possible similarities to 5% TEA-ibuprofen and 3) TEA was replaced with several different compounds, maintaining a I: I molar ratio with ibuprofen, to compare the surface activity of various ibuprofen salts. The surface tension and relative tensile strengths for each of these entities will be presented but are not included here due to spatial constraints.

C � C 0 'ii C .. I- ! 2007 ANNUAL SCIENTIFIC SEMINAR Figure 1. Autotensiomat Recording Showing Post-Peak Tailing "Relative Tensile Strength" 72.0 dynet/cm 31.5 dynes/cm f Relative Tensile Strength Chart Divisions a. 5% TEA-ibuprofen/water � C .2 ! • I- ! ::r en t Chart Divisions b. Water Discussion 553 A nonionic surfactant was not found having a surface tension low enough or surface viscosity high enough to compete with or overcome the interfacial dominance of TEA-ibuprofen. However, increased surfactant concentrations were found to reduce the surface viscosity of TEA-ibuprofen (e.g. 5% vs. 1 % ceteareth-20). With the exception of sodium lauroyl lactylate (1 % aqueous solution=50 chart divisions) none of the anionic surfactants exhibited a comparable tensile strength to that of TEA-ibuprofen. Comparison of the chemical structures of TEA-ibuprofen and sodium lauroyl lactylate reveals common propionate groups and adjacent chemical structures having significant electrophilic character an aromatic group in TEA-ibuprofen and an ester group in sodium lauroyl lactylate. Organic structures having significant electrophilic character are known to orient flat at the interface. The electron cloud of an aromatic ring or a carboxyl group is such a structure. Their large size and orientation prevent formation of a close-packed interfacial film that results in the highly elastic interfacial film. This retards diffusion of the emulsifier into the fatty amphiphile and ultimately results in a thinner cream consistency. All the ibuprofen salts tested had similar surface tensions (range 31.5-36.0 dynesh.m). The surface viscosity/tensile strength of TIPA-ibuprofen was high (48 chart divisions), but the Quadrol and sodium salts had very low tensile strength characteristics (2 and 5 chart divisions, respectively). The low tensile strength of the Quadrol and sodium head groups is attributable to steric hindrance in the case of Quadrol or electronic repulsion in the case of the sodium salt. Conclusions Stabilization of the emulsion was improved by the use of Promulgen D, a combination of cetearyl alcohol and ceteareth-20. However, TEA-ibuprofen continued to dominate the surface as demonstrated by the delayed viscosity development of the cream (2). It was found that delayed consistency development is not totally dependent on the surface activity of the emulsifier and TEA-ibuprofen. Therefore, two mechanisms have been proposed: I) the Promulgen D may be undergoing a delayed hydration in accordance with the gel network theory (1) or 2) the kinetics of TEA-ibuprofen replacement with Promulgen D at the interface is very slow. Further process development work has indicated that the consistency development can be accelerated by changing the order of addition of the oil and water phase components, adding the drug solution after emulsion formation, or increasing the emulsification temperature to 95°C. References 1. G.M. Eccelston, Cosmetics and Toiletries, 92 (2), 21-28 (1911). 2. L.E. Pena, B.L. Lee and J.F. Stearns, Journal of the Society of Cosmetic Chemists, 44, 337-345, (1993).