Effect of Formulation Factors on &lt;i&gt;In Vitro&lt;/i&gt; Permeation of Diclofenac from Experimental and Marketed Aqueous Eye Drops through Excised Goat Cornea

Ahuja, Munish; Dhake, Avinash S.; Majumdar, Dipak K.

doi:10.1248/yakushi.126.1369

Cited by 32 publications

(28 citation statements)

References 15 publications

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“…At the physiological pH of eye it primarily exists in ionized form and thus has limited permeability. A significantly higher corneal permeation of diclofenac was observed from solutions buffered to a lower pH (6.0) (10). Since reducing the pH also leads to precipitation, a number of approaches like use of solubilizer like polyoxyethylene-35-castor oil, and hydroxypropyl-β-cyclodextrin (33) have been employed.…”

Section: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

“…Using a combination of methylparaben and propylparaben as preservatives has been found to be favorable for corneal permeation. On the other hand employment of any one of the preservatives likes sorbic acid, benzyl alcohol, thiomersal and phenylmercuric acetate has been found to adversely affect the in vitro corneal permeation of diclofenac (10). Benzalkonium chloride at 0.01% (wt/vol) concentration is incompatible with diclofenac 0.1% (wt/vol) solution (10).…”

Section: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

“…On the other hand employment of any one of the preservatives likes sorbic acid, benzyl alcohol, thiomersal and phenylmercuric acetate has been found to adversely affect the in vitro corneal permeation of diclofenac (10). Benzalkonium chloride at 0.01% (wt/vol) concentration is incompatible with diclofenac 0.1% (wt/vol) solution (10). However, several marketed diclofenac ophthalmic solutions containing benzalkonium chloride (0.02%, wt/vol) were clear and the formulations showed enhanced permeation of drug through excised cornea.…”

Section: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

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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: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

Section: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

Section: Aryl Acetic Acid Derivatives Diclofenacmentioning

confidence: 99%

See 1 more Smart Citation

Topical Ocular Delivery of NSAIDs

Ahuja

Dhake²,

Sharma

et al. 2008

AAPS J

Self Cite

188

148

View full text Add to dashboard Cite

show abstract

“…The main photodecomposition product was identiˆed as 8-chloro-9H-carbazole-1-yl-acetic acid. 10) The in vitro corneal permeation characteristics of diclofenac from formulated aqueous 11) and oily 12) ophthalmic solutions of diclofenac have been investigated earlier. The purpose of the present investigation was to conduct stability studies on the aqueous and oily ophthalmic solutions of diclofenac.…”

Section: Introductionmentioning

confidence: 99%

Stability Studies on Aqueous and Oily Ophthalmic Solutions of Diclofenac

Ahuja

Dhake²,

Sharma

et al. 2009

YAKUGAKU ZASSHI

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Various aqueous and oily diclofenac ophthalmic formulations were subjected to accelerated and long term stability studies. Degradation of diclofenac was found to followˆrst-order kinetics. Among the aqueous formulations containing preservative, formulation with PMA, PMN, SA, MP/PP and SMS showed diclofenac content above 90％ after 6 months of accelerated and 12 months of room temperature storage. Diclofenac 0.1％, w/v aqueous formulation (pH 7.4), with 5 10％ overages, containing SMS, MP/PP or PMN look promising taking both stability and corneal permeability in view. However, for use in cataract surgery formulation without preservative appears ideal. Oily ophthalmic formulations except those in olive and mustard oil, had more than 90％ drug content after 6 months of accelerated and 12 months of room temperature storage. Diclofenac (0.2％, w/v) ophthalmic solution in sesame oil with 3％ overage and containing benzyl alcohol (0.5％, v/v) as preservative, appears ideal, taking both stability and corneal permeability in view.

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“…15) However, no such information is available on corneal permeation of diclofenac from oily solution. In the present study, the corneal permeation of diclofenac from oily solutions was investigated.…”

Section: Introductionmentioning

confidence: 99%