Preparation and comparison of antibiotic inserts by electrospinnig and solvent casting as potential ocular drug delivery vehicles

Shiva Taghe,1,* Shahla mirzaeei,2

1. Student Research Committee School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2. Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Introduction

Ciprofloxacin (cpfx) is a fluoroquinolone antibiotic against external infections of the eye, such as conjunctivitis, bacterial keratitis and keratoconjunctivitis. in addition to high potency, a desirable characteristic of topical fluoroquinolones is that concentration of the antibiotic should be maintained for sufficient long time above the minimum inhibitory concentration for relevant pathogens. efficacy of the ophthalmic fluoroquinolone products, mostly aqueous solutions, is limited by poor ocular bioavailabilitz, compelling the frequent dosing regimen and the concomitant patient compliance. drug delivery systems that improve the time spent staying on the cornea can have a significant impact. the recovery time before the cornea can increase the absorption of drugs through the perylum tissue. the availability of an improved drug can reduce the frequency of drug use. ophthalmic inserts are defined as sterile preparations, with a thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into cul-de-sac or conjuctival sac and whose size and shape are especially designed for ophthalmic application. nanofibers (nfs) are ultrafine solid fibers notable for their very small diameters. they have significantly large surface area to volume ratio, porosity, surface functionality, and superior mechanical properties. sodium alginate was chosen as a vehicle for ophthalmic formulations since it exhibits several favourable biological properties such as biodegradability and non-toxicity. a prolonged precorneal residence of formulations containing alginic acid was looked for, not only because of its ability to gel in the eye, but also due to its mucoadhesive properties. several researchers have developed nanofibers of pva by electrospinning because pva has good fiber-forming characteristics. the aim of the present work was to develop cpfx loaded ocular nanofiber and solvent cast polymeric inserts (scis) composed of blends of pva, and alginate and evaluate and comparison of their potential for ophthalmic drug delivery.

Methods

Nanofiber and solvent cast inserts of ciprofloxacin were fabricated using a blend of alginate (alg) and poly-vinyl alcohol (pva) contained 10% drug. for preparation of nanofibers, pva-alg solutions were loaded with the flow rate of 1.5 ml/h in to a 10 ml syringe attached to a circular-shaped polyethylene capillary tube with an inner diameter of 0.1 mm. the high voltage supply of 30kv was applied to the metallic needle, and the aluminum foil was used to collect the electrosprayed samples. nozzle to collector distance was adjusted to 18 cm. for solvent cast polymeric inserts ( scis) preparation, the pva-alg solutions were poured on an acrylic mold and were placed on a leveled surface at 60°c temperature and let dry for 12 h. inserts were characterized for morphology, thickness, infrared (ir) spectroscopy, and in vitro drug release. ciprofloxacin concentration was determined spectrophotometrically at λmax of 275nm.the inserts were sterilized by uv radiation for 15 minutes and tested for sterility.

Results

Nanofibers were found to be smooth, homogeneous and uniform. the smooth surface of nfs would be favorable for the ocular use compared to non-homogenous and rough surface scis. the rough surface of scis was also evident from the sem image. scis were found to be brittle and posed difficulty in handling. on the contrary, nfs possessed good folding endurance and this makes the insert safe and comfortable for ocular use. the thicknesses of cpfx-loaded nfs were found to about 100 μm, respectively with good folding endurance. inserts prepared using the solvent casting technique was brittle with thickness values greater than 200 μm. the inserts were found to be sterile for up to 30 days. in case of scis and nfs, the major peaks observed in the spectrum of the inserts are due to either alg or pva. the error bars in nfs are smaller representing the consistent and predictable release of the drug from inserts. the cpfx loaded nfs exhibited sustained release of the drug for more than 36 hours and could be used as a suitable alternative for treating of external infections of the eye.

Conclusion

Based on the results obtained, we conclude that nanofibers are better than inserts obtained by solvent casting technique and could be utilized as a potential delivery system for treating anterior segment ocular diseases and are capable of delivering drugs in a sustained.

Keywords

Nanofibers, ocular drug delivery, ciprofloxacin, solvent cast polymeric inserts.