Pharmacopoeias’ and manufacturers’ requirements for the quality of hard gelatin capsule shells

INTRODUCTION. The lack of national requirements regulating the quality of empty hard gelatin capsule shells (before filling with medicines) causes difficulties not only for capsule developers and manufacturers but also for experts evaluating regulatory submissions. This necessitates a comparative analysis of Russian and international requirements for the quality of hard gelatin capsule shells in order to draft a pharmacopoeia monograph on empty hard gelatin capsule shells. AIM. This study aimed to analyse the level of quality requirements for hard gelatin capsule shells, the selection of quality attributes for testing, and the applicable methods and analytical procedures for the preparation of a draft monograph for the State Pharmacopoeia of the Russian Federation. DISCUSSION. The results of this study indicate that the growing interest of manufacturers in producing capsule formulations is due to a number of features and advantages of this dosage form. Monographs on empty hard gelatin capsule shells are available in the State Pharmacopoeia of the Republic of Belarus, the Indian Pharmacopoeia, the Pharmacopoeia of the People’s Republic of China, the Korean Pharmacopoeia, and the Japanese Pharmacopoeia. The pharmacopoeial requirements for hard gelatin capsule shells include testing for quality attributes, such as description, identification (gelatin, titanium dioxide, dyes, and preservatives), odour, average capsule mass, disintegration, loss on drying, microbiological quality, impurities (sulfate ash, heavy metals, and arsenic), and preservatives (parabens and sulfur dioxide). Compared with other pharmacopoeias, the pharmacopoeias of Belarus and China provide the most detailed approach to the control of hard gelatin capsule shells. According to the materials of registration dossiers for 65 medicinal products formulated as capsules, the hard gelatin capsule shells that are most frequently used in Russia are produced by eight manufacturers. The specifications of these manufacturers include all the common quality attributes described in the pharmacopoeias and additional tests for arsenic and lubricants. CONCLUSIONS. The results of this comparative analysis of pharmacopoeial quality standards and manufacturers’ specifications for hard gelatin capsule shells justify the selection of the necessary quality attributes, limits, and requirements for inclusion in the draft monograph on empty hard gelatin capsule shells.