Forced degradation studies of corticosteroids with an alumina-steroid-ethanol model for predicting chemical stability and degradation products of pressurized metered-dose inhaler formulations.

An alumina (Al(2)O(3))-steroid-ethanol model is used for forced degradation testing of corticosteroids to predict chemical stability and degradation products in pressurized metered-dose inhaler (pMDI) solution formulations. The model involves an ethanolic solution of a test steroid with Al(2)O(3), stressed at elevated temperatures to mimic the chemical interaction of drug, excipient, and packaging (an aluminum aerosol canister). The reactivity order of eight synthetic corticosteroids toward Al(2)O(3)-induced reactions is ranked with the stress model. The corticosteroids containing a C21-OH group possess the highest reactivity, suggesting that aluminum canisters with an inert interior coating are needed to stabilize their solution pMDIs. The Al(2)O(3)-induced degradation products and degradation pathways of a steroid containing C21-OH and triamcinolone acetonide are presented, and the role of Al(2)O(3) in the degradation pathways is briefly discussed. A potential degradation profile of beclomethasone dipropionate (BDP) established with an Al(2)O(3)-BDP-ethanol stress model is the same as the actual degradation profile of the BDP pMDI product, indicating that the model indeed predicts the degradation products.