Interactions of theophylline with cyclodextrins in water

Abstract

Theophylline (1,3-dimethylxanthine, Figure 1), a poorly water soluble purine alkaloid, is widely used in medicine.1,2 The use of pure theophylline is limited by its very fast absorption and conversion into inactive metabolites. Moreover, theophylline in high doses causes unwanted side effects.3 To remove these disadvantages, coated controlled-release theophylline tablet formulations have been obtained in recent years. Acrylic and ion-exchange resins, paraffin, ethyl cellulose4–6 and cyclodextrins (CDs)7–9 were proposed as coating and encapsulating materials. The use of CDs as solubilising and stabilising agents is based on their ability to form inclusion complexes with organic substrates.10 The most commonly used α-, βand γ-cyclodextrins consist of six to eight glucopyranose units, respectively, and possess hydrophilic exterior and hydrophobic internal cavity. Placing inside the CD molecular cavity the substrate can considerably improve physico-chemical and pharmacological properties (solubility, stability, bioactivity, etc.).