Fraction of Zinc as Zn2+ Ions at Physiologic pH 7.4
Fraction of Zinc as Zn2+ Ions from Several Compounds at Physiologic pH 7.4 with Discussion
The only relevant pH in common cold therapy with zinc lozenges is the 7.35 to 7.4 range. All acids and other bases are quickly buffered to that pH range in blood, lymph, and tissue. Acid-base balance in body tissues and fluids is carefully regulated in a state of good health and is always maintained within normal physiologic limits.
The 7.4 pH of blood and extracellular fluid is close to the natural 6.8 pH of 20 mMol zinc acetate, suggesting good absorption potential as well as close approximation to laboratory pH conditions.
The candy base or compressed tablet base of a zinc lozenge must not react with the source of Zn2+ ions at physiologic pH to remain stable in efficacy, flavor and appearance. Chloride (from zinc chloride) and simple sugars have the same stability constant (log K1 = 0.00) for Zn2+ ions and react with each other. Even though zinc chloride lozenges release 100 percent of their zinc as Zn2+ ions in water, about fifty percent of the zinc from zinc chloride is bound with the sugars while in the solid lozenge form and form small brown spots on otherwise white lozenges. Zinc chloride lozenges are hygroscopic because zinc chloride is extremely hygroscopic. On the other hand, zinc acetate is ten times more strongly bound than zinc ions and simple sugars and it does not react with them, even though it releases 100 percent of its zinc as Zn2+ ions. Not shown are sugar alcohols which are slightly less than mid way between zinc chloride and zinc acetate. Consequently zinc acetate lozenges in simple sugars and sugar alcohols are stable over long periods of time and in all respects (availablity of Zn2+ ions, flavor, appearance (no color change) and they are not hygroscopic.
When using zinc lozenges, salivary proteins complex with and precipitate some Zn2+ ions at salivary pH, while some zinc is swallowed, and some is absorbed into oral and oropharyngeal tissues and is held at pH 7.4. Once absorbed, some Zn2+ ions are chelated by blood, lymph, and tissue while others remain in a hydrated ionic form. Whether or not a given amount of a zinc compound can 1) provide sufficient Zn2+ ions to be antirhinoviral in nasal tissue, 2) induce local interferon production, 3) provide local cell membrane stabilization, and 4) provide Zn2+ ions for the numerous other physiologic interactions at pH 7.4 is determined by the chemical stability of the zinc complex. Only absorbed Zn2+ ions available at pH 7.4 migrating from oral tissues into nasal and nasopharyngeal tissues are useful in shortening common colds. Consequently, there is a minimum dosage that may not have an obvious effect, such as a ZIA 10 strength lozenge, while at higher doses, such as ZIA 100 strength, colds are shortened by seven days if the lozenges are used each 2 hours.
Zinc compounds having very low stability constants such as zinc acetate release useful amounts of Zn2+ ions at pH 7.4, while zinc compounds with higher stability constants do not. For example, at pH 7.4, 100% of the zinc from zinc acetate (log K1 = 1.03) remains as hydrated Zn2+ ions, while only 30% of the zinc from zinc gluconate remains as Zn2+ ion (log K1 = 1.70). The availability of Zn2+ ions from zinc sulfate, lactate, malate, maleate, tartarate, and succinate (log K1 = 1.8 to 2.8) ranges in effect from less than desirable to useless for treating colds. Essentially no Zn2+ ions occur at pH 7.4 from zinc citrate, oxide, glutamate, tartarate, carbonate, glycinate, orotate, amino acid chelates, EDTA, and other highly chelated zinc compounds (log K1 = 4.5 to 16.5) as soluble or insoluble zinc complexes, rendering these compounds completely useless in treating colds.