654 N. ,4. `4rmstrong, `4. Bialkowska and J. Smith elution. Exceptions were found, however. Sulphate and thiosulphate, both effective eluents in the present study were reported as being ineffective, as were chloride and bromide. No mechanism was suggested by Mutch to support either his findings or their exceptions. Structures for hydrated aluminium hydroxides have been postulated by Thomas and co-workers. Individual alumina units are joined by hydroxide ions to give two- or three- dimensional polymeric structures, the process being termed 'olation'. Thomas and Whitehead (5) noted that on storage of alumina suspensions, changes in solubility occurred, and the liquid phase became more acidic, this being attributed to a hydrolytic process (Fig. 3a). The addition of neutral electrolytes, however, caused an increase in pH, the magnitude of the change being dependent on the salt used. For example, Thomas and Tai (6) studied the effect of seven potassium salts, and found that the magnitude of increase in pH was in decreasing order, oxalate, sulphate, acetate, iodide, bromide, chloride, nitrate. This was explained in terms of anion penetration, the anion displacing a hydroxo (H,O) or ol (OH) group, the latter causing the increase in pH (Fig. 3b). It was found that in general, salts of multivalent acids raised pH to a much greater extent than the salts of corresponding monovalent acids (7). L .,..H n-I • OH- L / 0 n • • ./ X L •H20[ '-H+ [ •H• +H+ l'/H20---'] + X• L n-1 +HaO +OH- Figure 3. Proposed mechanisms for (a) hydrolysis and (b) ardon p•nctrafion •n hydrated alumina structures [dcd¾cd from Thomas and W•tchcad (5)]. It is probable that a similar mechanism can explain the elution of F.D. & C. Blue No 1 dye from its lake. The degree of elution depends firstly on the valency of the anion, and within any valency group, the order of elution is comparable to that described by Thomas and Tai. This is confirmed by a study of the pH changes in the supernatant during the elution process where a high degree of elution is associated with an increase in supernatant pH. For example, water which shows negligible elution is associated with a fall in pH of 1.4 after 4 h, whilst almost all electrolytes which cause elution are associated with a rise in supernatant pH of between 0.5 and 1.5 units. The only exception to this is sodium succinate where a fall of 0.9 units is obtained. This is probably explained by the high starting pH 68.90) and the buffering capacity of the electrolyte itself. These elution effects are not associated with the disruption of the alumina lattice structure itself, which is stable between pH 3 and pH 9 (8). If electrolytes are used whose solutions give pH values outside this range, however, then elution will occur which is due to dissolution of the alumina substrate. Thus sodium phosphate and aluminium chloride

Leaching of F. D. & C. Blue No 1 dye 655 (the pH values of 0.5 M solutions of which are 12.2 and 3'1 respectively) are both associated with the rapid appearance of a large amount of the dye in the supernatant, but this effect will be acheived, at least in part, by disruption of the alumina itself. This mechanism may also be involved with sodium succinate (pH of a 0.5 M solution = 8.9). Between pH values of 3 and 9, however, the pH value itself is of minor importance. Table I shows the degree of elution at pH 4, 6 and 8, these pH values being achieved by either buffering with Teorell and Stenhagen citrate-borate-phosphate buffer, or by the addition of small amounts of •/10 hydrochloric acid or sodium hydroxide (i.e. an unbuffered system). The buffered suspensions show a much higher degree of elution at any given pH. This indicates that rather than pH per se, it is the presence of the buffer electrolytes used to achieve that pH which is the primary eluting factor. (Teorell and Stenhagen's buffer at pH 4 for example, contains approximately 0.06 M of sodium as borate, citrate and phosphate, all of which are stated by Mutch to be effective eluting electrolytes). pH changes, also shown in Table I, are those expected if the anionic pene- tration mechanism proposed by Thomas and Tai is appropriate in this case. Table I. Variation with pH of the elution of F.D. & C. Blue No 1 dye from its lake after 24 h, using (a) buffered and (b) unbuffered systems Original pH Buffered system Unbuffered system Elution (•o) pH change Elution (•o) pH change 4.0 98.4 4-1.35 4.4 4- 0'9 6.0 96.2 4-1.00 7.9 -0.85 8.0 94.0 +0.50 9.3 - 2.55 Water pH 7.0 -- -- 1.08 - 1.65 (control) The significance of this data in formulation is considerable. Small amounts of electrolyte impurities present in the dye itself or other associated solids may cause elution, particularly when the quantity of water present is also small, since in that case, reasonably concentrated electrolyte solutions may readily be achieved. Also the con- centration of electrolytes in human perspiration (0.03 M, 0'02 M, and 0.07 M with respect to chloride, phosphate and sulphate), may well cause a significant degree of dye elution. REFERENCES 1 Jaffe, J. and Lippmann, I. Inhibitory effect of gums and adsorbants upon the migration of F.D. & C. Blue No 1 in lactose. J. Pharm. $ci. 53 441 (1964). 2. Armstrong, N. A. and March, G. A. Quantitative assessment of surface mottling in colored tablets. J. Pharm. $ci. 63, 126 (1974). 3 Goodhart, F. W., Everhard, M. E. and Dickcius, D. A. Stability of certified dyes in tablets. J. Pharrn. $ci. 53 338 (1964). 4 Mutch, N. Dried alumina. Quart J. Pharrn. Pharrnacol. 19 490 (1946). 5 Thomas, A. W. and Whitehead, T. H. Ion interchanges in aluminium oxychloride hydrosols. J. Phys. Chern. 35 27 (1931). 6 Thomas, A. W. and Tai, A. P. The nature of aluminium oxide hydrosols. J. Am. Chern. Soc. 54 841 (1932). 7 Whitehead, T. H. The complex compound theory of colloidal oxides. Chern. Rev. 21 113 (1937). 8 Armstrong, N. A. and Clarke, C. D. The adsorption of crystal violet by kaolin. J. Pharrn. Pharrnacol. 23 955 (1971).