In vitro transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic ointment.

Transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic ointments was studied in vitro, using goat cornea. Cumulative (%) permeation of ketorolac through cornea, was found to be maximum with 0.2% (w/v) ketorolac drops in sesame oil followed by formulations in corn oil and soyabean oil. Ketorolac 1% (w/v) drops in castor oil increased the quantity permeated but cumulative (%) permeation was less. Permeation profiles of ketorolac were in consistence with the partition characteristic of drug between oil and aqueous phase. Formulations favouring corneal permeation of ketorolac increased corneal hydration. Addition of benzyl alcohol, a preservative, to oil drops reduced permeation of ketorolac and corneal hydration indicating possible protective effect of benzyl alcohol against corneal damage. Permeation studies on ointment formulations containing either ketorolac acid or ketorolac tromethamine salt indicated better permeation for formulation containing ketorolac tromethamine aqueous solution. Thus for better transcorneal permeation, ketorolac 0.2% (w/v) drops, formulated in sesame oil, containing 0.5% v/v benzyl alcohol and ophthalmic ointment containing 0.5% (w/w) ketorolac tromethamine in dissolved state appear suitable.

In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops.

In vitro transcorneal permeation of ketorolac tromethamine from 0.5% w/v solutions containing equimolar (0.02 M) concentrations of citrate (pH 6.5), phosphate (pH 6.5 and 7), citrate-phosphate (pH 7) and borate (pH 7) buffers was studied using goat cornea. Cumulative % permeation was maximum with phosphate buffered drops of pH 6.5. The effect of pH and ionic strength on permeation of ketorolac tromethamine from buffered (phosphate) drops was next investigated. Cumulative % permeation of ketorolac tromethamine from buffered drops was pH dependent being maximum at pH 4.5. Adjustment of ionic strength of drops to 0.2 resulted in decreased permeation of drug. Permeation of ketorolac tromethamine from unbuffered drops of varying pH and ionic strength 0.2 was also pH dependent and was maximum at pH 4.5. Buffered drops of pH between 4.5-5.5, ionic strength 0.2, provided better permeation of drug compared to unbuffered drops of same pH and ionic strength. Above pH 6.5 unbuffered drops showed better permeation than buffered drops. Increase in molarity of phosphate buffer (pH 4.5) used in making drops, between 0 to 0.15 M increased permeation. Aqueous drops of ketorolac tromethamine formulated in 0.15 M phosphate buffer of pH 4.5 and ionic strength 0.2 showed maximum cumulative % permeation in vitro. Considering lacrimation induced drug loss in vivo, by buffer of high concentration, ketorolac tromethamine drops formulated in buffer of low molarity, pH 4.5 and ionic strength 0.2 appear suitable.

Wound healing profiles of ketorolac, metronidazole and tinidazole administered post-surgically.

On dead space wounds, drugs (ketorolac, metronidazole and tinidazole) caused a significant (P < 0.01) decrease in breaking strength, granulation tissue weight and hydroxyproline content in male rats. Both the parameters of excision wound were significantly (P < 0.01) hastened by metronidazole and tinidazole only. Post operative management of wounds with ketorolac (a potent analgesic), metronidazole and tinidazole (for anaerobic infections) may be dealt with the risk of a delay in healing. Both metronidazole and tinidazole promote the epithelization process.

A multiple dose comparison of ketorolac tromethamine with ibuprofen for analgesic activity.

This study was done to compare a new analgesic ketorolac with ibuprofen in post-operative and post-laparoscopy pain. A total of 40 patients were recruited for the study of which 20 were post-operative and 20 were post-laparoscopy cases. Medication was given over a period of 48 hours after surgery and a pain score based on subjective symptoms was monitored at fixed intervals after each dose. The analgesic efficacy of ketorolac was found to be comparable to that of ibuprofen and the drug was well tolerated in the doses used without any extra medication being required.

Comparative evaluation of tolmetin & tolmetin-zinc on wound-repair & inflammation.

In view of the reported healing-suppressant activity of some NSAIDs and absence of this adverse effect in their zinc-complexes, tolmetin (Tol), a recently introduced NSAID and its zinc-complex (Tol-Zn) were compared for their wound healing and antiinflammatory profiles in male albino rats. Tolmetin-zinc (Tol-Zn) significantly reversed (P less than 0.01) the suppressant effect of Tol on gain in breaking strength of skin incisions and dead space wounds (breaking strength, g: for control, Tol and Tol-Zn were: 313 +/- 7, 250 +/- 11, 294 +/- 16 in skin wounds; 244 +/- 7, 137 +/- 18, 195 +/- 16 in dead space wounds). Tol-Zn shared the significant (P less than 0.001) suppressant effect of Tol on granuloma formation (granuloma weight, mg: control - 69 +/- 3, Tol - 36 +/- 3.03, Tol-Zn - 37 +/- 2.75) and its collagen content (total hydroxyproline per tissue, microgram: control - 1955 +/- 55, Tol - 1400 +/- 200, Tol-Zn - 1410 +/- 150). Rat paw edema induced by carrageenin was significantly (P less than 0.001) reduced by Tol as well as Tol-Zn. In the chronic model both the agents suppressed significantly (P less than 0.001) granuloma formation by 50 per cent. Zinc sulphate by itself reduced the rat paw edema by 39 per cent (P less than 0.02) and did not affect the other parameters. Zinc-complex appears to be an improved version of tolmetin as an antiinflammatory agent with no adverse effect on the healing process. Tolmetin-zinc promotes gain in breaking strength, not by increasing the collagen content, but by favouring better maturation of available collagen at the wound site.