Improvement of drug loading onto ion exchange resin by cyclodextrin inclusion complex

Abstract

Context: Ion exchange resins have ability to exchange their counter ions for ionized drug in the surrounding medium, yielding “drug resin complex.” Cyclodextrin can be applied for enhancement of drug solubility and stability.

Objective: Cyclodextrin inclusion complex of poorly water-soluble NSAIDs, i.e. meloxicam and piroxicam, was characterized and its novel application for improving drug loading onto an anionic exchange resin, i.e. Dowex^® 1×2, was investigated.

Methods: β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex with drugs in solution state at various pH. The inclusion complex was characterized by phase solubility, continuous variation, spectroscopic and electrochemistry methods. Then, the drug with and without cyclodextrin were equilibrated with resin at 1:1 and 1:2 weight ratio of drug and resin.

Results and discussion: Solubility of the drugs was found to increase with increasing cyclodextrin concentration and pH. The increased solubility was explained predominantly due to the formation of inclusion complex at low pH and the increased ionization of drug at high pH. According to characterization studies, the inclusion complex was successfully formed with a 1:1 stoichiometry. The presence of cyclodextrin in the loading solution resulted in the improvement of drug loading onto resin.

Conclusions: Enhancing drug loading onto ion-exchange resin via the formation of cyclodextrin inclusion complex is usable in the development of ion-exchange based drug delivery systems, which will beneficially reduce the use of harmful acidic or basic and organic chemicals.

Keywords::

• Resinate
• drug loading
• ion exchange resin
• cyclodextrins
• inclusion complex

Acknowledgements

The authors wish to thank the Commission of Higher Education (Thailand), the Thailand Research Funds through the Golden Jubilee PhD Program (Grant No. PHD/0001/2553) and the Silpakorn University Research and Development Institute (Grant No. SURDI 55/02/12).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper