Elemental Impurities in Gelatine Capsules: Human Health Risk Assessment

Abstract

INTRODUCTION. This work continues the authors’ earlier study on gelatine capsule contamination with elemental impurities, which resulted in proposing a list of elements for standardisation. To ensure the safe use of medicinal products in this dosage form, it is necessary to develop criteria for the quantitative assessment of potential human health risks associated with elemental impurities in gelatine capsule shells.AIM. This study aimed to determine the permitted daily concentration (PDC) limits for elemental impurities in gelatine capsules from a risk-based pharmaceutical quality control perspective.MATERIALS AND METHODS. The authors analysed their previous experimental data, the relevant Russian State Standard (GOST), the requirements of the State Pharmacopoeia of the Russian Federation and leading world pharmacopoeias (USA, UK, EU, China, Japan, and India), and the scientific literature published from 1980 to 2023 on the content of elemental impurities (Al, As, Cd, Cu, Cr, Cr, Fe, Hg, Mn, Pb, and Zn) in gelatine capsule shells and medical gelatine.RESULTS. When standardising the content of elemental impurities in gelatine capsule shells, it is necessary to consider not only the toxicity of impurities but also their potential to compromise the quality of gelatine. Complexing elements (Cd, Cu, Hg, Cr, and Zn) can affect the quality of gelatine at subtoxic concentrations. For Cd, Cu, and Hg, the authors recommended using the PDC limits specified in GOST 23058-89 Gelatine. Raw materials for the medical industry. Specifications. For Cr and Zn, the authors recommended adhering to the PDC limits specified in the State Pharmacopoeia of the Russian Federation, edition XIV, Monograph 2.1.0099.18 Gelatine. Lead affects the quality of gelatine at concentrations above the toxicity threshold, and arsenic does not cause clustering of gelatine molecules. For Pb and As, the authors recommended using the PDC limits specified in the State Pharmacopoeia of the Russian Federation, edition XV, General Monograph 1.1.0040 Elemental impurities. The authors proposed a conversion factor to account for the complexing potential of Al when limiting its content in gelatine capsule shells. The authors recommended assessing the risks to human health associated with Mn intake with gelatine capsule shells indirectly by listing total heavy metals as a quality attribute to be controlled at the level of medical gelatine. The content of Fe should also be standardised at the raw material level.CONCLUSIONS. The content of elemental impurities in gelatine capsule shells should not exceed the following limits: 45 µg/g for Al, 1.5 µg/g for As, 0.03 µg/g for Cd, 10 µg/g for Cr, 15 µg/g for Cu, 0.05 µg/g for Hg, 0.5 µg/g for Pb, and 30 µg/g for Zn. The standardisation of these elements in gelatine capsule shells will prevent negative effects on the human body and shell quality.