Physicochemical characterization and in vitro permeation studies of thalidomide and its n-alkyl analogues.

摘要

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with high levels of tumour necrosis factor-alpha (TNF-alph) in synovial fluid and synovial tissue~1. Thalidomide is a proven inhibitor of the biologicla synthesis of TNF-alpha~2 and is believed to rely on this action for its suppression of the wasting of tissue, which accompanies RA. Oral administration of thalidomide has proven to be effective in RA, but unacceptable side effects are easily provoked~3. Administration of thalidomide via the dermal route can down-regulate TNF-alpha production in and around the affected joint and this without raising the systemic blood level to a problematical level. Based on thalidomide's physicochemical properties, it is unlikely that it can be delivered percutaneously at a dose required for RA. Therefore, the purpose of this study was to determine the permeation parameters of thalidomide and its N-alkyl analogues as a step towards predicting their potentials for formulating into percutaneous delivery systems. The intent was also to establish a correlation between the physicochemical properties of these compounds and their percutaneous rates of absorption.