Zinc Acetate as Source of Zn2+ Ions
Although zinc gluconate is the best known source of Zn2+ ions in lozenges for treating common colds, zinc acetate merits special attention. Zinc acetate has chemical properties preferable over zinc gluconate for use in zinc lozenges. For example, zinc acetate dihydrate is 29.7 percent zinc and anhydrous zinc acetate is 35.5 percent zinc, compared with 13.14 percent zinc in zinc gluconate. Only 77.23 mg zinc acetate is needed to provide 23 mg zinc, compared with 175 mg of zinc gluconate. Over 400 grams of zinc acetate will dissolve in a liter of water compared with 100 grams/liter for zinc gluconate. Zinc acetate has a considerably lower stability constant than zinc gluconate (log K1= 1.03 vs. 1.70) under identical laboratory conditions.(1) Zinc acetate releases 100 percent Zn2+ ions as no reasonable complexation occurs between zinc and acetate in solutions up to 20 mMol, at any pH between 2.8 and 7 and, a fortiori, far above (Figure 20).(2) Zinc acetate is 3.33 times as ionizable as zinc gluconate at tissue pH 7.4. Zinc acetate was used in vitro by Korant and co-workers at Du Pont to inhibit replication of rhinoviruses.(3) Zn2+ ion, from zinc acetate, is as antirhinoviral and as protective of mono-layer cells in vitro as interferon.
Figure 20. Concentration of Zn2+ ion in the zinc and acetate system by pH. Zinc and acetate are present at 10 mMol. Acetate protonation curves in the presence and absence of zinc were found to be exactly super-imposable. Regardless of pH, Zn2+ ion concentration (log K1=1.0) is essentially 100%, with some zinc acetate+ of a low stability constant (log K1=1.7) possibly forming at higher pH. From data by Hacht and Berthon.(2) and personal communication August 2, 1999.
It is fully capable of stabilizing cell membranes and closing pores in cells induced by cytolytic agents. The increased availability of Zn2+ ions at pH 7.4 allows Zn2+ ion concentration to be sufficiently high to produce high ZIA values even when used in sugar lozenges producing large amounts of saliva. Therapeutic doses may be astringent but need not be orally irritating. When 5 to 23 mg of zinc from zinc acetate is compounded into 5-gram sugar-based lozenges, lozenges have ZIA values from about 30 to 200 and are flavor-stable and have pleasant tastes.
Along with a much larger amount of available Zn2+ ion, flavor stability is another extremely important property of zinc acetate as demonstrated over multi-year high temperature, summer storage conditions. For example, zinc acetate directly compressed lozenges, in a base of crystalline fructose and agglomerated sucrose (Mendell's Sugartab(r)) and also containing 14 mg sodium saccharin and peppermint oil retained a pleasant sweet taste and had no objectionable aftertaste after a 3-year storage period in ambient conditions cycling from 120 degrees F. in summer to 30 degrees F. in winter. Similar findings were produced using a tablet base of pure fructose agglomerated with polyethylene glycol 8000, although a color change occurred. In numerous other experiments, zinc acetate compressed lozenges with various carbohydrate bases did not become bitter upon aging or thermal cycling over a 3-year period.
When a pharmaceutically acceptable carrier is sweet, lozenge taste is good. Zinc acetate lozenges do not become bitter upon aging in the presence of fructose, sucrose, or dextrose. Flavor stability is independent of moisture content: whether lozenges are moist to the touch or dry, flavor is not affected regardless of time. Flavor-stability is an outstanding property of zinc acetate lozenges. Moreover, no discoloration of packaged lozenges has been noted during storage, suggesting high chemical stability.
Acceptability of zinc acetate in zinc lozenges was completely unexpected, because undiluted zinc acetate has a dreadfully vile taste completely offensive by any standard and much worse than the taste of undiluted zinc gluconate. The acetic acid complex of zinc might be expected to smell and taste like vinegar. Crystals do smell like vinegar, but lozenge compositions are completely devoid of any vinegar smell or taste. Zinc acetate compositions never have the long-lasting and offensive aftertastes typical of zinc gluconate compositions.
Flavor Stability