818 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tion (an oxidation-reduction procedure), rather than by atomic absorption or other methods not distinguishing between tin II and IV, because the stannous ion is more active than the stannic ion (6). The fluoride ion is usually sep- arated by diffusion and determined electrometrically or colorimetrically (6). These analyses will give precise data on the soluble ions chemically avail- able as a function of dentifrice formulation, pH, temperature, and time. It is important to recognize that both stannous and fluoride ions contribute to the anticaries activity (8,9). If a formulation is selected to sacrifice the stannous ions, then sodium fluoride should be chosen as the active ingredient. In fact, the stannous ion does inhibit some of the fluoride from reacting with enamel (8). If the stannous ion stability is of prime concern, why not tie it up in a com- plex which will provide indefinite stability? This situation is not unlike the difference between investing money in a growth situation or placing it in a freeze. Complexes will increase stability, but this may be accomplished at the expense of clinical availability. Thus, a decision must be made in an effort to balance chemical stability and clinical availability. Admittedly the two fac- tors are not mutually exclusive, and chemical instability would result in a lack of clinical availability. Polarography (6, 10) would be the natural laboratory tool to study the strength of complexes. However, such studies would not provide direct information on the availability of the stannous ion to dental enamel. CLINICAL EVALUATION As physical and chemical data are accumulated on fi•e active ingredient alone and in its projected formulations, it is necessary to select methodology to define the clinical availability of the active ingredient to the clinical sub- strate, the tooth. The selection of in vitro and in vivo test methodology to de- fine bioavailability is dependent upon the multiplicity of variables present in the human use situation. No one test should be expected to satisfy the evalua- tion rcquirements of one or several active ingredients in suitable vehicles. The most direct approach to the measurement of stannous and fluoride ion availability from dentifrice formulations to enamel would appear to be ion up- take studies (11). There is very little of this type of data in the published literature. The two main reasons for this situation would appear to be the dif- ficulty of measuring ion uptake from dentifrice slurties under use conditions, ( 12, 13) and the availability of other methods such as enamel solubility tests, •vhich are sensitive to the ion levels in dentifrices. Since the prime mode of dental caries attack is acid dissolution of tooth structure, one of the most frequently used criteria for evaluation of anticaries activity has been the use of enamel solubility reduction (ESR) procedures. The types and modifications of the ESR are extensive. In a review of ESR tests and their significance to dental caries, Brudevold and McCann (14) con-

THERAPEUTIC DENTIFRICES 819 eluded that enamel dissolution testing was useless in predicting clinical ef- fectiveness of anticaries agents. One of the major concerns of these authors •vas the number of false positive results. Nevertheless, the judicious selection of operational variables integrated into a group of test procedures (14) can provide the desired information on bioavailability. A wide variety of powdered enamel solubility tests have been described in the literature (15). One procedure useful with dentifrice slurries is that de- scribed by Gershon (16). Since the dissolution rate is dependent upon parti- cle size (Fig. 1), powder passing a 125-mesh sieve and held up on a 225-mesh sieve was used. Enamel powder treated with dentifrice slurries was then freed of the dentifrice ingredients by simply rinsing the enamel powder on a 225- mesh sieve. Some of the problems arising with powdered enamel include: reduction of surface area due to reaction with active ingredient, decrease in particle size due to add dissolution during the test, contamination of the pow- der with treatment reaction products, and difficulties in observing changes in the physical characteristics of the substrate (15). With powdered enamel as well as other substrates, it is important to determine the full dissolution pro- file of all treated substrates (Fig. 2). These curves are necessary for selection of spedfie test conditions which may be used for routine screening (Pig. 8). 24 2O "' 16 o 12 10 20 30 40 50 60 70 80 90 MINUTES Figure I. Dissolution curves of powdered human dental enamel with three different par- ticle sizes, (100-200) passing 100-mesh and retained by 200-mesh sieve, (200-325) passing 200-mesh and retained by 325-mesh sieve, and (325) passing 325-mesh sieve