Use of the antioxidant BHT in asymmetric membrane tablet coatings to stabilize the core to the acid catalyzed peroxide oxidation of a thioether drug.
The application of a controlled-release asymmetric membrane (AM) coating containing cellulose acetate and polyethylene glycol 3350 (PEG3350) to a stable osmotic tablet core resulted in the oxidative degradation of active ingredient located in the core. It was hypothesized that the production of hydroperoxides from PEG3350 in the coating was responsible for the electrophilic oxidation of drug to the sulfoxide degradation product. The type and solubility of carboxylic acid excipient used to formulate the drug release profile of the osmotic tablet significantly influenced the amount of oxidation. By adding the antioxidant butylated hydroxytoluene (BHT) to the coating, oxidation was significantly inhibited in tablets placed on accelerated stability. Of three additives that were used to prevent oxidation [BHT, ferrous sulfate, and ethylenediaminetetraacetic acid (EDTA)], BHT was shown to be the most effective at preventing sulfoxide formation. The BHT was also shown to be more effective in the coating rather than in the core due to its location closer to the source of the oxidizing species, PEG3350, in the coating.
Puz
Michael J
MJ
Pharmaceutical Research and Development, Exploratory Pharmaceutics Group, Pfizer Global Research and Development, La Jolla, CA 92121, USA. michael.puz@pfizer.com
Johnson
Barbara A
BA
Murphy
Brendan J
BJ
D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000737:chemistry* / Q000378:metabolism; D010545:Peroxides / Q000737:chemistry* / Q000378:metabolism; D013440:Sulfides / Q000737:chemistry* / Q000378:metabolism; D013608:Tablets, Enteric-Coated
D000975:Antioxidants; D010545:Peroxides; D013440:Sulfides; D013608:Tablets, Enteric-Coated; D002084:Butylated Hydroxytoluene