Silicon is one of the most monitored inorganic elements in extractables and leachables (E&L) studies of pharmaceutical packaging systems and related components. There is an urgency to evaluate toxicological threshold of silicondueto the direct contact of drug products (DP) especially a liquid form of DP with thewidely used pharmaceutical packaging systems made of silicon materials, for instance, glass and silicone. It is also required by the Center for Drug Evaluation (CDE) of National Medical Products Administration in China to test thesilicon content in DP to investigate glass delamination in E&L studies. Specifically, oral toxicity is low for inorganic silicon like silicon dioxide or organic silicon polymers such as silicon tube/silicone oil (polydimethylsiloxane, or namely PDMS as the major ingredient).In comparison, inhalational toxicity of silicon dioxide leads to pulmonary silicosis or even lung cancer. In the case of the parenteral route of administration, the toxicity of silicon dioxide, glass, polymers or PDMS oligomers varies depending on their morphology or degrees of polymerization. Overall, the toxicities of organic silicon compounds vary due to their different molecular weight (MW). PDMS with high MW has minimal toxicsymptoms by both intra-peritoneal and subcutaneous administration routes, yet it is worth noting the difficulty of degradation and elimination of PDMS. For intravenous administration route, exposure to either PDMS or small molecule dimethyl silicone compoundsmay lead to death. Finally, our work determines permitted daily exposure (PDE) of 93 μg·d-1 for inorganic silicon and 100 μg·d-1 for organic silicon by reviewing toxicological data of both forms of silicon. This work aims to provide evidences and references for pharmaceutical companies and regulatory agencies on the PDEs of silicone elements through a variety ofadministration routes.
HAO Peng-chao, WANG Ying-ying, WANG Jin-hui, GUO Bin, SUN Xiong-fei, ZHANG Le-shuai
. Review on silicon toxicityin the compatibility study of pharmaceutical packaging and process components*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(9)
: 1493
-1504
.
DOI: 10.16155/j.0254-1793.2022.09.02
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