Microparticle systems based on polymer-drug interaction for ocular delivery of ciprofloxacin I. In vitro characterization

Abstract

The interaction of polyelectrolytes with oppositely charged drugs can result in a reduction of polymer solubility and the formation of microparticles. Treating conjunctivitis with conventional eye drop formulations of ciprofloxacin (CPX) hydrochloride requires instillations at least three to four times a day. Patient compliance and drug efficacy can be significantly improved by increasing the residence time of the formulation in the conjunctival sac. This can be achieved by using a microparticle system, especially if coadministered with mucoadhesive polymers capable of interacting with both the formulation and the precorneal mucus. In this study, a microparticle system based on CPX and chondroitin sulphate (CS) was developed by slowly stirring aqueous solutions of CS into drug solutions. Ionic interaction between the drug and the oppositely-charged polymer resulted in a very fine precipitate (CPX/CS) from which the drug is released after the ions in the medium are displaced. The objective of this study was the in vitro characterization of CPX/CS microparticles, with particular attention to drug polymer interaction and particle size. The behavior of CPX/CS in a tear system model was assessed for comparison with a commercial eye drop solution. Mucoadhesive polymers such as carbomer, Na carboxymethylcellulose, gelatin and hydroxypropylcellulose were added to improve mucoadhesion. The effect of these polymers on drug release was also studied.