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 55
- Downloads 0
Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer
SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na+-coupled manner....
Technical Pitfalls and Improvements for High-speed Screening and QSAR Analysis to Predict Inhibitors of the Human Bile Salt Export Pump (ABCB11/BSEP)
Drug-induced hepatotoxicity is one of the major problems encountered in drug discovery and development. Selection of a candidate compound for pre-clinical studies in the drug discovery process is a critical step that can...
Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer
In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentrat...
Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and Solutions
Empirical Bayes (“post hoc”) estimates (EBEs) of ηs provide modelers with diagnostics: the EBEs themselves, individual prediction (IPRED), and residual errors (individual weighted residual (IWRES)...
Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer
Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a...