Determination of Elemental Impurities in Gelatine Capsules by Inductively Coupled Plasma Mass Spectrometry

Abstract

INTRODUCTION. Gelatine capsules are an essential dosage form used for many medicinal products. Gelatine capsules are subject to quality control in accordance with the requirements of the general monograph on capsules of the State Pharmacopoeia of the Russian Federation. This monograph does not standardise the content of elemental impurities, as these impurities are controlled at the raw material level. However, the equipment and excipients used in the production of gelatine capsule shells may be additional sources of impurities. Preliminary screening for chemical elements will help to assess the need for limiting elemental impurities in gelatine capsule shells.AIM. This study aimed to identify the chemical elements that contribute to gelatine capsule shell contamination the most by inductively coupled plasma mass spectrometry, to list the elements requiring specification, and to limit their content from a risk-based pharmaceutical quality control perspective.MATERIALS AND METHODS. The study used 18 samples of hard gelatine capsules by different national and international manufacturers. The elemental analysis was performed using an Agilent 7900 inductively coupled plasma mass spectrometer (Agilent Technologies).RESULTS. The As, Ba, Co, Cr, Cu, Li, Mo, Ni, Pb, Sb, and V content in gelatine capsule shells did not exceed the permitted daily exposure (PDE) thresholds for oral dosage forms specified in the State Pharmacopoeia of the Russian Federation. Ag, Au, Cd, Hg, Ir, Os, Pd, Pt, Rh, Se, Sn, or Tl were not detected in any of the samples within the established detection limits. The Fe content in 67% of the tested shell samples was above the safety-based PDE for medical gelatine.CONCLUSIONS. The greatest contributors to gelatine capsule shell contamination are Al, Fe, and Zn. The lack of established PDE thresholds for these elements presents a challenge in assessing the risks of adverse effects associated with ingesting these elements with gelatine capsules.

Keywords

• gelatine capsules
• medical gelatine
• elemental impurity composition
• content standardisation
• risk assessment
• inductively coupled plasma mass spectrometry
• elemental content screening