Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: A technical note

Malhotra, Manjusha; Majumdar, Dipak K.

doi:10.1208/pt070496

Cited by 17 publications

(7 citation statements)

References 16 publications

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“…Prolonged topical use of the formulations did not produce any gastrointestinal ulceration in rats, a common side effect associated with NSAIDs due to PG inhibition, which suggests safety of the products on chronic administration (52).…”

Section: Ketorolacmentioning

confidence: 88%

Topical Ocular Delivery of NSAIDs

Ahuja

Dhake²,

Sharma

et al. 2008

AAPS J

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188

148

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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 propionicand 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.

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Section: Ketorolacmentioning

confidence: 88%

Topical Ocular Delivery of NSAIDs

Ahuja

Dhake²,

Sharma

et al. 2008

AAPS J

Self Cite

188

148

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“…Prostaglandins are one of the primary eicosanoids released upon insult to the canine eye (Maggs, 2008). After biosynthesis, prostaglandins bind to receptors called pain facilitators (Tranquilli and Thurman, 1999;Marfurt et al 2001), which promote variations in the resting potential of neuronal membranes. These variations in membrane resting potentials result in pain amplification (Bloom, 1996;Tasaka, 1999;Acosta et al, 2005;Tranquilli and Thurman, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, higher mean sensitivity values were obtained when compared to other study treatments during the same time point, which may represent a potentially higher corneal irritant effect. This finding was interesting, as a change in corneal sensitivity was not expected because benzalkonium chloride is a preservative devoid of anti-inflammatory properties and is instead used in ophthalmic solutions to increase drug penetration through the lipid cell membrane (Madhu et al, 1996;Malhotra and Majumdar, 2006). It is also an ingredient present in ketorolac ophthalmic solution.…”

Section: Introductionmentioning

confidence: 99%

Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs

Cantarella¹,

Oliveira²,

Dorbandt³

et al. 2017

Open Vet J.

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To evaluate corneal sensitivity by using the Cochet-Bonnet® esthesiometer in normal canine eyes at different time points following instillation of three different topical non-steroidal anti-inflammatory drugs (flurbiprofen sodium 0.03%, diclofenac sodium 0.1% and ketorolac tromethamine 0.5%) and benzalkonium chloride 0.01%. Six healthy mixed breed dogs from the same litter were used in two different stages. First, one drop of flurbiprofen sodium 0.03% and diclofenac sodium 0.1% in each eye; second, one drop of ketorolac tromethamine 0.5% and benzalkonium chloride 0.01% in each eye. Baseline esthesiometry was obtained before eye drop application and every 15 minutes thereafter until a total of 105 minutes of evaluation time. A one-week interval was allowed between the two treatment phases. Statistical analysis was used to compare means according to time of evaluation and drug used. Diclofenac sodium 0.1% decreased corneal sensitivity at 75 and 90 minutes (P > 0.015) with possible interference on neuronal nociceptive activity and analgesic effect while ketorolac tromethamine 0.5% did not show any variation for esthesiometry means along the evaluation. Flurbiprofen sodium 0.03% resulted in increased esthesiometry values 30 minutes after instillation (P > 0.013), increasing corneal sensitivity and possibly producing a greater irritant corneal effect over its analgesic properties. Benzalkonium chloride 0.01% significantly increased corneal sensitivity at 15 minutes of evaluation (P > 0.001), most likely resulting from its irritating effect. Esthesiometry did not allow a definite conclusion over the analgesic effect of the NSAIDs tested; however it was effective in detecting fluctuations in corneal sensitivity.

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“…All eyes were then evaluated for parameters of inflammation (i.e. lid closure extent and polymorphonuclear leukocyte (PMN) migration) (Gupta et al, 2000;Malhotra & Majumdar, 2006).…”

Section: Methodsmentioning

confidence: 99%

Glycerogelatin-based ocular inserts of aceclofenac: Physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation

Mathurm

Gilhotra

2010

Drug Delivery

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Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: A technical note

Cited by 17 publications

References 16 publications

Topical Ocular Delivery of NSAIDs

Topical Ocular Delivery of NSAIDs

Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs

Glycerogelatin-based ocular inserts of aceclofenac: Physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation

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Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: A technical note

Cited by 17 publications

References 16 publications

Topical Ocular Delivery of NSAIDs

Topical Ocular Delivery of NSAIDs

Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs

Glycerogelatin-based ocular inserts of aceclofenac: Physicochemical, drug release studies and efficacy against prostaglandin E2-induced ocular inflammation

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Glycerogelatin-based ocular inserts of aceclofenac: Physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation