The potential impact of interactions between zinc ions and excipients on absorption is very difficult to predict.5 While typical tablet diluent (e.g., microcrystalline cellulose) and disintegrant (e.g., colloidal anhydrous silica or crospovidone) excipients are not expected to have a significant impact on absorption due to either minimal reactivity or being present in limited quantities, sweeteners are a significant concern. As is indicated in the 2007 WHO publication entitled Production of Zinc Tablets and Zinc Oral Solutions: Guidelines for Programme Managers and Pharmaceutical Manufacturers, products may contain one or more suitable flavours and sweeteners in order to improve acceptability but, these substances “should not impair the bioavailability or the therapeutic efficacy or safety of the preparation.” In order for a waiver from in vivo studies to be considered, applicants must provide evidence that the sweeteners employed would not negatively affect the absorption of zinc from the formulation. Such evidence can come from either literature or in vitro studies, such as comparative absorption data from cells or infused intestines. Similar information concerning other excipients may be requested during assessment if sufficient information concerning the excipients(s) and their impact on zinc absorption is not available to the Prequalification Team medicines.
