International journal of pharmaceutics

Migration of antioxidant additives from various polyolefinic plastics into oleaginous vehicles.

PMID 12711176


The migration of the antioxidant additives pentaerythrityl tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (Irganox 1010) and tris(2,4-di-tert-butylphenyl)phosphite (Irgafos 168) from polyolefinic packaging into oily vehicles was investigated. The polyolefins included in the study were from the following classes: isotactic polypropylene homopolymer (PP), ethylene-co-propylene random copolymer (RACO), ethylene-propylene heterophasic copolymer and ethylene-propylene amorphous copolymer blend (EP) and high-density polyethylene (HDPE). Each polymer was additioned with Irganox 1010 (0.15%, w/w) and Irgafos 168 (0.15%, w/w) and processed into blown bottles. To study the antioxidant release process, plastic sheets were cut from the bottles and dipped for various time intervals into a mixture of five oils (caprylic/capric triglyceride, cyclomethicone, dicaprylyl ether, isohexadecane and C(12-15) alkyl benzoate) representative of lipophilic excipients used in pharmaceutical and cosmetic formulations. After exposure to the oil medium, the non-migrated Irganox 1010 and Irgafos 168 were recovered from the polymeric matrices using microwave-assisted extraction with ethyl acetate-hexane and assayed by HPLC. The leaching of the two antioxidants varied remarkably depending on the polyolefin crystallinity and structure. The amount of Irganox 1010 transferred into the contact medium at 25 degrees C decreased in the order EP>RACO>PP>HDPE. The same polyolefin ranking was observed in the case of Irgafos 168, except for PP and HDPE which exhibited similar depletion of this additive. Migration of Irgafos 168 was greater than that of Irganox 1010 and the release of both antioxidants increased at higher temperature (50 degrees C). The obtained data are useful for the selection of polyolefinic matrices as raw-materials for the production of pharmaceutical and cosmetic containers.