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The effect of the inclusion of several concentrations of surface-active agents in four different types of ointment bases on the percutaneous absorption of salicylic acid and sodium salicylate was determined. Hydrophilic ointment, petrolatum, hydrophilic petrolatum containing water, and polyethylene glycol ointment were modified either by varying the concentration of surface-active agent present in the U. S. P. XV formula, or by adding varying amounts of surface-active agents to those bases in which none was originally present. Sorbitan monostearate, polyoxyethylene 20 sorbitan monostearate, and polyoxyethylene 40 stearate were studied as representative of lipophilic and hydrophilic surface-active agents of the nonionic type. The results indicate a correlation between percutaneous absorption and the degree of interaction of the polyoxyethylene groups present in the hydrophilic surface-active agents with the salicylates.

Forty-eight substances and combinations were studied for their possible effectiveness as preservatives for solutions of nonionic surfactants of the sorbitan partial fatty acid ester and polyoxyethylene ester types. Results indicated that sorbic acid (0.2 per cent w/v); phenylmercuric borate (0.007 per cent w/v); phenylmercuric nitrate (0.01 per cent w/v); phenylmercuric acetate (0.007 per cent w/v); n -trichloromethylmercapto-4-cyclohexene-1,2-dicarboximide (Vancide® 89 RE, 0.04 per cent w/v); diethylene glycol monomethyl ether (methyl Carbitol, 3 per cent w/v); hexylene glycol (3 per cent w/v); and benzalkonium chloride (0.1 per cent w/v) are effective in preserving these solutions. The failure of various phenolic preservatives to preserve these surfactant solutions is attributed to complex formation between phenolic and polyether groups. Studies on various cosmetic formulations containing nonionic surfactants indicate that sorbic acid (0.2 per cent w/w) and combinations of sorbic acid and hexylene glycol are effective preservatives. These preservatives were also found effective in products containing sorbitol as well as nonionic surfactants.

An approach to the evaluation of the percutaneous absorption of drugs from ointment bases is described. Salicylic acid and sodium salicylate were selected as test drugs for incorporation into ointment bases representing each of four physical types of ointment vehicles. These ointments were applied to the intact shaved skin of the rabbit and confined by a specially designed bandage. Concentration of salicylate in the blood was determined at hourly intervals following application of the ointment. Salicylic acid was most effectively absorbed from hydrophilic ointment. The extent of absorption from the other ointments studied, in decreasing order, was: hydrophilic petrolatum containing water, petrolatum, and polyethylene glycol ointment. Sodium salicylate was also absorbed to the greatest extent from hydrophilic ointment, although the degree of absorption was considerably less than that observed with salicylic acid. On the basis of salicylate blood levels, no significant absorption of sodium salicylate occurred from ointments prepared with petrolatum, hydrophilic petrolatum containing water, or polyethylene glycol ointment.

Ointment bases have been prepared utilizing Na, K, Ca, Mg, H, and Volclay bentonites as major constituents of these bases. Observations are reported on the relative swellin power of these bentonites, and the color intensity and pH of their bases. Anti-inkctive ointments were prepared utilizin these bases as carriers for the drugs, and studies of the bacteriological activity of tfese ointments are reported. These ointments show greater antibacterial activity than their respective U.S. P. and N. F. ointments. Sulfathiazole, phenol, and ammoniated mercury showed greater activity when incorporated into a H bentonite base than when these drugs were incorporated into the other bentonite bases.

The stability of vitamin B 12 was studied in aqueous solutions of sorbitol, glycerin, dextrose, and sucrose. Solutions were kept at 25°, 45°, and 100° for periods up to one hundred and forty days. Vitamin B 12 content was determined spectrophotometrically using an absorption maximum of 361 mμ. It was found that vitamin B 12 is compatible with sorbitol and glycerin at 25° and 45°. Dextrose and sucrose solutions were found to cause the loss of vitamin B 12 in solution. Dextrose was more destructive to the vitamin than was sucrose.

Glycerin and sorbitol were found to supplement each other in their inhibition of both molds and bacteria. It is believed that this inhibitory action is purely one of osmotic effect. Propylene glycol appears to have a specific inhibitory effect against bacteria and most molds; the addition of 10% w/v propylene glycol was found to inhibit the growth of these organisms. Thirty per cent w/v propylene glycol is required to inhibit Monilia albicans. Studies have indicated that the inhibition produced by the addition of propylene glycol to sorbitol solutions is not purely the result of osmotic effect, as is the case with glycerin, but probably one related to its chemical structure. It may, therefore, be concluded that propylene glycol has a significant and useful preservative activity in many preparations including those made with sorbitol.