THERAPEUTIC DENTIFRICES 821 8O 7O 6O 5O 4O 3O 2O \\ e• % ESR - A-B A= UNTREATED ENAMEL TREATED ----? I0 20 30 40 50 60 MINUTES Figure 3. Dissolution curves of powdered human dental enamel treated with dentifrice- water (1: 3) slurries in pH 4, 0.2M acetate buffer X--- X Control ß • ß Stannous fluoride paste A •x iX Stannous fluoride paste B with known caries-producing microorganisms, the reproducibility of animal studies in defining anticaries activity is increased (21). After complete physical and chemical characterization of the active ingre- dient alone and in its dentifiice formulation, demonstration of anticaries ac- tivity for the formulation in experimental animals, and determination of bio- availability by a combination of carefully chosen in vitro and in vivo tests, the question arises of what else must be done to prove anticaries effectiveness. The immediate response has been two, or better three, clinical studies lasting 3 years with several hundred children. Even this quantity of clinical evidence may not be adequate for a new type of active ingredient. The initial review of the stannous fluoride dentifrice data was based upon seven clinical studies (22). How much data is required for minor modifications of an existing den- tifrice system which has already been demonstrated to be clinically effective?

822 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS IO0 F Mean and Range Mean and Range for 68 runs for 58 runs SnF2 SOLUTIONS• t. .001 .005 .01 .02 o NaF SO L UTION.•._.•.•,_.._.• I I I .05 .04 05 CONCENTRATION of F7 M Figure 4. Dissolution curves oE intact human dental enamel treated with sodium and stan- nous fluoride solutions [from (9)] Certainly if clinical studies are required to verify laboratory documented im- provements of the basic dentifrice system, few if any of these improvements will be made or utilized. Because of the widespread availability of anticaries agents, it is becoming increasingly difficult to conduct a clinical study. It will become more difficult to establish clinical anticaries activity. For this reason, continued emphasis must be placed on the design of the clinical study to maximize the information received and clinical studies should be undertaken only when the need is in- dicated. There must be greater reliance upon definitive laboratory studies. The basis for this greater reliance upon laboratory studies is the correlation of experimental data of the new product with the clinically established prod- uct. Comparison with activity of the stannous fluoride dentifrices seems in- dicated. LABORATORY EVALUATION Laboratory data on sodium fluoride and monofluorophosphate are less ex- tensive than those for stannous fluoride and probably less impressive. Since these compounds have been demonstrated to be clinically effective (5) with an activity somewhat comparable to stannous fluoride dentifrices, then new laboratory procedures must be developed to assess this activity. The following methods have been useful in characterizing dentifrice formu- lations containing stannous fluoride. The enamel solubility test is a good meas-