• Nadia Morsi Cairo University
  • Dalia Ghorab Cairo University
  • Hanan Refai Cairo University
  • Hoda Teba Misr University for Science and Technology


Ketorolac tromethamine, Nanodispersions, Alginate, Chitosan, Sustained release, Permeation


Objective: Preparation and characterization of ketorolac tromethamine (KT)-loaded alginate/chitosan nanodispersions for ocular sustained drug delivery and improved transconeal permeation.

Methods: Alginate/chitosan KT-loaded nanoparticles were formulated using different techniques; modified coaservation and ionotropic pregelation. The nanodispersions were evaluated for particle size, zeta potential, entrapment efficiency and in-vitro release. The formula with optimum physicochemical characteristics was tested for stability as well as ex-vivo transcorneal permeation in comparison to marketed eye drops (Acular®).

Results: In both techniques, increasing the concentration of chitosan showed a significant increase in particle size. However, increased size with increasing the amount of alginate was significant in modified coaservation method but non-significant in ionotropic pregelation method. The ionotropic pregelation method generally resulted in nanoparticles with smaller sizes. The values of zeta potential were highly influenced by the alginate/chitosan ratio in both methods as the high amount of alginate shifted the zeta potential to be negative, and the absolute value increased by increasing its concentration. The entrapment of KT into nanoparticles prepared by ionotropic pregelation method was found to be significantly lower than those prepared by modified coaservation method. All the nanodispersions showed an initial burst release followed by a more gradual and sustained-release phase. Alginate NPs significantly retarded the release of KT and showed higher transcorneal permeation when compared with Acular®.

Conclusion: Ionotropic pregelation method produced nanodispersions for all tested alginate/chitosan ratios with sustained KT release and improved transcorneal permeation.



Download data is not yet available.


Thakur RR, Kashiv M. Modern delivery systems for ocular drug formulations: A comparative overview WRT conventional dosage form. Int J Res Pharm Biomed Sci 2011;2:8-18.

Prow TW. Toxicity of nanomaterials to the eye. Wiley Interdiscip Rev: Nanomed Nanobiotechnol 2010;2:317-33.

Bhattacherjee P. The role of arachidonate metabolites in ocular inflammation. Prog Clin Biol Res 1989;312:211-27.

Ahuja M, Dhake AS, Sharma SK, Majumdar DK. Topical ocular delivery of NSAIDs. AAPS J 2008;10:229-41.

Hirneiß C, Neubauer AS, Kampik A, Schönfeld C-L. Comparison of prednisolone 1%, rimexolone 1% and ketorolac tromethamine 0.5% after cataract extraction. Graefes Arch Clin Exp Ophthalmol 2005;243:768-73.

Malhotra M, Majumdar DK. In vivo ocular availability of ketorolac following ocular instillations of aqueous, oil, and ointment formulations to normal corneas of rabbits: A technical note. AAPS Pharm Sci Tech 2005;6:523-6.

Flach AJ, Kraff MC, Sanders DR, Tanenbaum L. The quantitative effect of 0.5% ketorolac tromethamine solution and 0.1% dexamethasone sodium phosphate solution on postsurgical blood-aqueous barrier. Arch Ophthalmol 1988;106:480-3.

Heier J, Cheetham JK, DeGryse R, Dirks MS, Caldwell DR, Silverstone DE, et al. Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: A randomized, vehicle-controlled clinical trial. Am J Ophthalmol 1999;127:253-9.

Fraser-Smith EB, Matthews TR. Effect of ketorolac on Pseudomonas aeruginosa ocular infection in rabbits. J Ocul Pharmacol Ther 1988;4:101-9.

Fu RC-C, Lidgate DM. In vitro rabbit corneal permeability study of ketorolac, tromethamine, a non-steroidal anti-inflammatory agent. Drug Dev Ind Pharm 1986;12:2403-30.

Parveen S, Sahoo SK. Polymeric nanoparticles for cancer therapy. J Drug Targeting 2008;16:108-23.

Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discovery Today 2003;8:1112-20.

Calvo P, Vila-Jato JL, Alonso MaJ. Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int J Pharm 1997;153:41-50.

Lehr C-M, Bouwstra JA, Schacht EH, Junginger HE. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 1992;78:43-8.

Mi F, Sung H, Shyu S. Drug release from chitosan–alginate complex beads reinforced by a naturally occurring cross-linking agent. Carbohydr Polym 2002;48:61-72.

Shah S, Pal A, Kaushik V, Devi S. Preparation and characterization of venlafaxine hydrochloride loaded chitosan nanoparticles and in vitro release of drug. J Appl Polym Sci 2009;112:2876-87.

Kulkarni PV, Keshavayya J. Chitosan-sodium alginate biodegradable interpenetrating polymer network (IPN) beads for delivery of ofloxacin hydrochloride. Int J Pharm Pharm Sci 2010;2 Suppl 1:77-82.

Sinha V, Singla A, Wadhawan S, Kaushik R, Kumria R, Bansal K, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm 2004;274:1-33.

Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P. Development of a new drug carrier made from alginate. J Pharm Sci 1993;82:912-7.

Mohammad pourdounighi N, Behfar A, Ezabadi A, Zolfagharian H, Heydari M. Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom. Nanomed: Nanotechnol Biol Med 2010;6:137-43.

Thwala LN. Preparation and characterization of alginate-chitosan nanoparticles as a drug delivery system for lipophilic compounds. University of Johannesburg; 2012.

Shafie M, Fayek H. Formulation and evaluation of betamethasone sodium phosphate loaded nanoparticles for ophthalmic delivery. J Clin Exp Ophthalmol 2013;4:1-11.

Challa R, Ahuja A, Ali J, Khar R. Cyclodextrins in drug delivery: an updated review. AAPS Pharm Sci Tech 2005;6:329-57.

Ibrahim MM, Abd-Elgawad A-EH, Soliman OA-E, Jablonski MM. Natural bioadhesive biodegradable nanoparticles-based topical ophthalmic formulations for sustained celecoxib release: In vitro study. J Pharm Technol Drug Res 2013;2:1-15.

Prabha S, Zhou W-Z, Panyam J, Labhasetwar V. Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles. Int J Pharm 2002;244:105-15.

Katara R, Majumdar DK. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf B 2013;103:455-62.

Schipper NG, Olsson S, Hoogstraate JA, VÃ¥rum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2:mechanism of absorption enhancement. Pharm Res 1997;14:923-9.

Van der Merwe S, Verhoef J, Verheijden J, Kotze A, Junginger H. Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. Eur J Pharm Biopharm 2004;58:225-35.

Dodane V, Amin Khan M, Merwin JR. Effect of chitosan on epithelial permeability and structure. Int J Pharm 1999;182:21-32.

Monti D, Saccomani L, Chetoni P, Burgalassi S, Saettone M. Effect of iontophoresis on transcorneal permeation ‘in vitro’of two β-blocking agents, and on corneal hydration. Int J Pharm 2003;250:423-9.

Shanmugam S, Ramvignesh T, Sundaramoorthy K, Ayyappan T, Vetrichelvan T. Design and evaluation of novel ophthalmic delivery system of aciclovir for herpes simplex infection. Res J Pharm Dosage Forms Technol 2011;3:52-6.



How to Cite

Morsi, N., D. Ghorab, H. Refai, and H. Teba. “PREPARATION AND EVALUATION OF ALGINATE/CHITOSAN NANODISPERSIONS FOR OCULAR DELIVERY”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 7, July 2015, pp. 234-40,



Original Article(s)