Ophthalmic drug delivery of ketorolac tromethamine by suitable polymeric nanofibers

Shahla Mirzaeei,1,* Shiva taghe,2

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

Abstract

Introduction

Ocular inflammation can be caused by a wide variety of factors, including autoimmune disease, infection, allergies, injury or trauma, and surgery. normally, treatment of ocular inflammation involves the use of corticosteroids and non-steroidal anti-inflammatory drugs (nsaids). ketorolac tromethamine (kt) is a non-steroidal anti-inflammatory drug from the family of heterocyclic acetic acid derivatives. aqueous ocular drops of kt are effective for topical use in inhibiting postoperative inflammation of the eyes, reducing postoperative pain, reducing conjunctivitis with no alteration of corneal opacity. the major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. also, the rapeutic drug levels are not maintained for longer duration in target tissues. in the past two decades, ocular drug delivery research advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. to overcome the ocular drug delivery barriers and improve ocular bioavailability, various conventional and novel drug delivery systems have been developed such as nanofibers, nanoparticles, liposomes, dendrimers, implants, contact lenses, nanosuspensions. nanofibers offer the prospects of prolonging the residence time of nfs ensuring optimal contact between the formulation and the mucosa resulting in adequate drug concentration in external ocular tissues. polycaprolactone (pcl) is the biodegradable and biocompatible in nature. therefore, the patch will degrade with time and come out. slow degradation rate of pcl makes it suitable for fabrication of nanofibers patch for prolonged drug delivery. the food and drug administration (fda) have approved pcl for use in the drug delivery. the objective of the present study was to develop ocular delivery for ketorolac tromethamine loaded polycaprolactone nanofibers used to treat inflammation of the eye.

Methods

Nanofibers solutions were obtained upon the composition of 10% pcl with ketorolac solved in dmf/acetone under magnetic stirring at room temperatures. preparation of the nanofibers was carried out using a customized electrospining system. the solutions were loaded with the flow rate of 1 ml/h and 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 28 kv 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. nanofibers characterized on the basis of fiber diameter, morphology, entrapment efficiency, percentage moisture absorption, percentage moisture loss, thickness, folding endurance and drug release behavior, etc. ketorolac tromethamine concentration was determined spectrophotometrically at λmax of 323nm.

Results

In the present work biodegradable polymeric nanofibers were successfully developed by using electrospinning technique. the microscopic study indicated that the nanofibers were uniform in diameter with smooth surface (197-230 nm). we achieved very high drug content about 100%. the insert had a thickness varying from 0.0766±0.0020 mm to 0.105±0.0020 mm. nanofiber inserts showed the good folding endurance, which revealed that nanofibers have enough flexibility and can easily get adjusted in ocular tissue. the folding endurance nanofiber formulations are in the range of 303±3 to 364±5. degree of swelling plays an important role in the drug release behavior from the nanofiber insert. the degree of swelling was found be high in case of pcl nanofibers. moisture uptake values were found to be in the range of 0.96±0.016 to 1.055±0.044 and the moisture loss values were found in the range of 1.01±0.027 to 1.24±0.054. the results revealed that nanofibers inserts have the good physical stability at high humid and dry conditions. in addition, the study has demonstrated a slower, sustained release of kt through cornea, as compared to the solution formulation of this drug (about 54h).

Conclusion

The physicochemical properties showed that the nanofibers could be an effective carrier for ketorolac. thus, this formulation of nanofibers has a strong potential for a sustained release effect of the drug, when applied to the eye topically.

Keywords

nanofibers, ocular drug delivery, polycaprolactone, electrospinning, ketorolac tromethamine.