Problems in Ophthalmic Drug Delivery: Evaluation of the Interaction Between Preservatives and Cyclodextrins

Today, the use of cyclodextrins (CDs) is a major concern in drug formulations to improve solubility and stability of compounds. It has been known that CDs can reduce the antimicrobial effectiveness of preservatives by formation of inclusion complexes.. In this study the interaction between commonly used preservatives, benzalkonium chloride (BZCl) or methyl paraben (MP), with synthetic CDs (HP γ-CD or SBE β-CD) in the presence or absence of ethylene diamine tetra acetic acid (EDTA), as a preservative potentiator, and fluorometholone was investigated.. The tests were performed during a 4 week period according to the preservative effectiveness test of USP 2010.. The results showed that CDs reduce the effectiveness of BZCl and MP even in the presence of drug molecules. The only exception was HP γ-CD 5% solution with BZCl and EDTA which was effective against tested microorganisms both in the presence and absence of drug molecules.. The solution of HP γ-CD 5% with BZCl 0.02% and EDTA 0.1% was selected as a good carrier for dissolving fluorometholone for use as an eye drop..