344 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS thermal arrests of the photomonitor recordings are sufficiently consistent with these values to verify the suspected identity of the agglomerates. Thermal and infrared trace substance analysis of an isolated agglomerate indicated cetyl palmitate to be the major component and stearyl and cetyl alcohol to be the minor components (11). The absence of isopropyl myristate in the trace substance analysis verifies the photomicroscopy observation that the oil and wax components phase separate as distinct entities. CONCLUSIONS The model cream was a white lotion at the time of manufacture that slowly converted to a semisolid consistency and subsequently became softer again as aging and the phase separation process progressed. The consistency development and destabilization were both associated with phase changes in the surfactant/fatty amphiphile systems. In the former case, surfactant interpenetrates the fatty amphiphiles in a semihydrate crystalline arrangement to form a fully hydrated, lameliar liquid crystalline gel network. In the latter case, the lameliar liquid crystal breaks down, expelling the fatty amphiphiles, which revert back to the crystalline semihydrate arrangement. The consistency changes reflect the integrity of the gel network since it is a highly viscoelastic system. The extent of destabilization is apparent in the degree of pearlescence, since the phase-separated fatty amphiphiles and waxes of the internal phase form light-refracting platelets. The consistency development and destabilization process can be monitored using rhe- ology and microscopy. Structural development is apparent in the rheograms by an increase in hysteresis and a shift toward higher yield values. However, once a semisolid consistency is established, the overall shape of the rheogram remains basically un- changed except for the shift to higher shear stress values. Destabilization appears in the rheograms through formation of spurs and secondary inflections, shifts to lower maxi- mum shear stress values, and changes in the size and shape of the hysteresis loop. General trends in the destabilization process show a low shear rate inflection, which gradually becomes more pronounced and shifts to higher shear stress values, and a recoil following the maximum shear stress, which shifts to lower shear rates. These changes reflect the destruction of a shear-resistant network and formation of a less shear-resistant network and can be correlated with breakdown of the lameliar liquid crystalline gel network, droplet coalescence, and agglomerate formation. The phase changes apparent in photomicrographs support the rheological findings. As the cream consistency develops, polarized light photomicrographs show a decreased presence of grainy textures (coagel or lipophilic gel) and increased formation and thick- ness of birefringent, lameliar structures (lameliar liquid crystalline gel phase or hydro- philic gel). Ordinary light shows gradual replacement of the grainy textures with emulsion droplets and improved definition of the droplets. These changes have been attributed to increased surfactant penetration of the fatty amphiphiles. Destabilization has been associated with formation of diffuse, weakly birefringent structures when viewed with polarized light. These areas also appear diffuse in ordinary light. The concentration of the diffuse, weakly birefringent structures has been found to increase as phase separation progresses. The pearlescence apparent in phase-separated creams has been attributed to these agglomerates that, according to theory (1,8), are structurally similar to coagel (i.e., lipophilic gel). The small oil droplets associated with the ag-

CONSISTENCY DEVELOPMENT OF A MODEL CREAM 345 glomerates suggest that the waxes and oils of the internal phase separate as distinct entities. Thermal optical videomicroscopy and trace substance analysis have identified the phase-separated components of the agglomerates as cetyl alcohol, stearyl alcohol, and cetyl palmitate. The absence of isopropyl myristate in the trace substance analysis has verified the conclusion that the oil and wax components phase separate as distinct entities. ACKNOWLEDGMENTS The authors wish to express their appreciation to D. S. Aldrich and T. M. Ryan for performing the trace substance analysis. REFERENCES (1) G. M. Eccleston, The microstructure of semisolid creams, Pharmacy International, 63-70 (March 1986). (2) B. •d. Barry and G. M. Ecclesron, Influence of gel networks in controlling consistency of O/•d emulsions stabilized by mixed emulsifiers, d. Texture Studies, 4, 53-81 (1973). (3) G. M. Eccleston, The influence of fatty alcohols on the structure and stability of creams prepared with polyethylene glycol 1000 monostearate/fatty alcohols, Int. J. Cosmet. Sci., 4, 133-142 (1982). (4) G. M. Eccleston, Structure and rheology of cetomacrogol creams: The influence of alcohol chain length and homologue composition, J. Pharm. Pharmac., 29, 157-162 (1977). (5) G. M. Eccleston, "Properties of Fatty Alcohol Mixed Emulsifiers and Emulsifying Waxes," in Ma- terials Used in Pharmaceutical Formulation.' Critical Reports on Applied Chemistry, A. T. Florence, Ed. (Blackwell Scientific Publications, London, 1984), Vol. 6, pp. 124-156. (6) B. W. Barry and G. M. Saunders, Kinetics of structure build-up in self-bodied emulsions stabilized by mixed emulsifiers, J. Coll. Interface Sci., 41, 331-342 (1972). (7) L. E. Pena, B. L. Lee, and J. F. Stearns, Secondary structural rheology of a model cream, Midwest Regional Meeting of the American Academy of Pharmaceutical Scientists, Chicago, May 15, 1989 (submitted for publication). (8) H. E. Junginger, Colloidal structures of O/W creams, Pharm. Weekbl. Sci. Ed., 6, 141-149 (1984). (9) H. K. Patel, R. C. Rowe, J. McMahon, and R. F. Stewart, A systematic microscopical examination of gels and emulsions containing cetrimide and cetostearyl alcohol, Int. J. Pharm., 25, 13-25 (1985). (10) The Merck Index, 10th ed, M. Windholz, Ed. (Merck and Co., Inc., Rahway, NJ, 1983), pp. 282, 1259. (11) T. M. Ryan and D. S. Aldrich, Internal memo--The Upjohn Company (December 8, 1989).