Topical Ocular Delivery of NSAIDs
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 2
Abstract
In ocular tissue, arachidonic acid is metabolized by cyclooxygenase to prostaglandins which are the most important lipid derived mediators of inflammation. Presently nonsteroidal anti-inflammatory drugs (NSAIDs) which are cyclooxygenase (COX) inhibitors are being used for the treatment of inflammatory disorders. NSAIDs used in ophthalmology, topically, are salicylic-, indole acetic-, aryl acetic-, aryl propionic- and enolic acid derivatives. NSAIDs are weak acids with pKa mostly between 3.5 and 4.5, and are poorly soluble in water. Aqueous ophthalmic solutions of NSAIDs have been made using sodium, potassium, tromethamine and lysine salts or complexing with cyclodextrins/solubilizer. Ocular penetration of NSAID demands an acidic ophthalmic solution where cyclodextrin could prevent precipitation of drug and minimize its ocular irritation potential. The incompatibility of NSAID with benzalkonium chloride is avoided by using polysorbate 80, cyclodextrins or tromethamine. Lysine salts and α-tocopheryl polyethylene glycol succinate disrupt corneal integrity, and their use requires caution. Thus a nonirritating ophthalmic solution of NSAID could be formulated by dissolving an appropriate water-soluble salt, in the presence of cyclodextrin or tromethamine (if needed) in mildly acidified purified water (if stability permits) with or without benzalkonium chloride and polyvinyl alcohol. Amide prodrugs met with mixed success due to incomplete intraocular hydrolysis. Suspension and ocular inserts appear irritating to the inflamed eye. Oil drop may be a suitable option for insoluble drugs and ointment may be used for sustained effect. Recent studies showed that the use of colloidal nanoparticle formulations and the potent COX 2 inhibitor bromfenac may enhance NSAID efficacy in eye preparations.
Authors and Affiliations
Munish Ahuja, Avinash S. Dhake, Surendra K. Sharma, Dipak K. Majumdar
Keywords
Related Articles
- EP ID EP681544
- DOI 10.1208/s12248-008-9024-9
- Views 81
- Downloads 0
A general procedure for the enantioselective synthesis of the minor tobacco alkaloids nornicotine, anabasine, and anatabine
The minor tobacco alkaloids nornicotine, anabasine, and anatabine fromNicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are relatively less potent than S-(−)-nicotine, the...
The Utility of Modeling and Simulation Approaches to Evaluate Immunogenicity Effect on the Therapeutic Protein Pharmacokinetics
While therapeutic proteins (TP), particularly recombinant human proteins and fully human monoclonal antibodies, are designed to have a low immunogenic potential in humans, a clinical immune response does sometimes occur...
Effects of Selected OATP and/or ABC Transporter Inhibitors on the Brain and Whole-Body Distribution of Glyburide
Glyburide (glibenclamide, GLB) is a widely prescribed antidiabetic with potential beneficial effects in central nervous system injury and diseases. In vitro studies show that GLB is a substrate of organic anion transport...
A combination of iontophoresis and the chelating agent 1, 10 phenanthroline act synergistically as penetration enhancers
The peroxovanadium compound VO(O2)2, 1,10 phenanthroline (bpV (phen)) is capable of lowering blood glucose levels. It is not available in oral form, but it is effective when delivered transdermally. Iontophoresis can sig...
High Sensitivity RT-qPCR Assay of Nonlabeled siRNA in Small Blood Volume for Pharmacokinetic Studies: Application to Survivin siRNA
The online version of this article (doi:10.1208/s12248-015-9812-y) contains supplementary material, which is available to authorized users.