300 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS z• Xl:X2=X3:O O- oeORNSTRRoeH •- MRGNESIUH STERRRTE +- PRESSURE .z2 ' -b.ss -b.54 -b.2• o'.t3 0',46 o'.so Figure 8. Computer generated plot of Time of Peak Plasma Concentration as a function of each independent variable. experimentation and subsequent analysis can lead not only to the optimum or most desirable product and process but, if carried far enough, can shed light on the mechanism by which the independent variables affect the product properties. There area appropriate statistical techniques by which such analyses can be carried out (13,14). The important concept is that by rational experimentation, the formulatot is able to learn more about his system and thus he is more able to control it. REFERENCES (1) J. B. Schwartz, Optimization techniques in pharmaceutical formulation and processing, in Modern Pharmaceutics, G. S. Banker and C. T. Rhodes, Eds., (Marcel Dekker, Inc., New York, 1979) Chapt. 17.

OPTIMIZATION TECHNIQUES 301 (2) M. H. Rubinstein, Optimising tablets by evolutionary operation techniques, Mfg. Chem. & Aerosol News (August, 1974), p. 30. (3) S. N. Deming and P. G. King, Computers and experimental optimization, Res. Develop. (May, 1974), p. 22. (4) E. Shek, M. Ghani and R. E. Jones, Simplex search in optimization of capsule formulation,J. Pharm. Sci., 69, 1135 (1980). (5) O. L. Davis (Ed.), The Design and Analysis of Industrial Experiments, (Hafner Press, New York, 1967). (6) G. E. P. Box and K. B. Wilson, On the experimental attainment of optimum conditions, J. Roy. Statist. Soc., B, 13, 1 (1951). (7) J. L. O'Neill and R. E. Dempski (unpublished data). (8) D. E. Fonner, Jr.,J. R. Buck and G. S. Banker, Mathematical optimization techniques in drug product design and process analysis,J. Pharm. Sci., 59, 1587 (1970). (9) J. R. Buck, G. E. Peck and G. S. Banker, Management science aids in expediting pharmaceutical product designs, Drug Develop. Commun. 1, 89 (1974-75). (10) J. B. Schwartz, J. R. Flamholz and R. H. Press, Computer optimization of pharmaceutical formulations. I. General procedure,J. Pharm. Sci., 62, 1165 (1973). (11) S. Dincer and S. Ozdurmus, Mathematical model for enteric film coating of tablets, J. Pharm. Sci., 66, 1071 (1977). (12) A. N. Karabelas, R. W. Mendes and J. B. Schwartz, Computer optimization of pharmaceutical formulations: Pharmacoki•etic parameter prediction, presented to the Industrial Pharmaceutical Technology Section, A.Ph.A. Academy of Pharmaceutical Sciences, San Antonio Meeting, Nov. 1980. (13) N. R. Bohidar, F. A. Restaino and J. B. Schwartz, Selecting key parameters in pharmaceutical formulations by principal component analysis,J. Pharm. Sci., 64, 966 (1975). (14) N. R. Bohidar, F. A. Restaino and J. B. Schwartz, Selecting key formulation factors by regression analysis, Drug Develop. and Ind. Pharm., 5, 1975 (1979).