Cyclodextrin complexation of NSAIDs: Physicochemical characteristics: physicochemical characteristics

The interactions of a number of NSAIDs, i.e. acetylsalicylic acid, ibuprofen, methyl acetylsalicylate, methyl salicylate, naproxen and tenoxicam, with five cyclodextrin (CD) derivatives, i.e. β-cyclodextrin (βCD), 2-hydroxypropyl-β-cyclodextrin with molar substitution of 0.6 or 0.9 (HPβCD MS 0.6 or 0.9), 2-hydroxypropyl-γ-cylcodextrin (HPγCD MS 0.6) and mixture of maltosyl/dimaltosyl-β-cyclodextrin (M/DMβCD), was investigated. All the NSAIDs tested formed inclusion complexes with the CDs but addition of ethanol or propylene glycol to the aqueous CD solutions reduced their degree of complexation. Also, ionization of the NSAIDs normally reduced the degree of complexation. However, CD complexation of ionized drug molecules can result in much larger total solubilization, i.e. solubilization of a drug both due to CD complexation and ionization, than if either method was used by itself. NMR studies of the complexation of salicylic acid and acetylsalicylic acid with βCD indicate that during the complex formation the benzene ring of the drug molecules goes into the cavity from the wider side of the βCD molecule. These studies also show that in the acetylsalicylic acid-βCD inclusion complex the benzene ring is located well inside the cavity and the acetyl group is outside the cavity. This complexation mechanism is also supported by degradation studies.