Ocular Bioavailability and Tissue Distribution of [14C]Ketorolac Tromethamine in Rabbits

Ling, Teck L.; Combs, Daniel L.

doi:10.1002/jps.2600760405

Cited by 42 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results correlate well with the corneal tissue half-lives of ketorolac, suggesting that the corneal epithelium may be acting as a reservoir for drug accumulation, similar to the situation reported for ketorolac 22 and pilocarpine. 23 Thus the longer half-lives observed in rabbits with intact corneas may be due to a continued flux of drug into the aqueous humor from the corneal reservoir as previously reported.…”

Section: Figure 1seffectsupporting

confidence: 81%

“…23 Thus the longer half-lives observed in rabbits with intact corneas may be due to a continued flux of drug into the aqueous humor from the corneal reservoir as previously reported. 22,23 Our results indicate that the corneal epithelium is important in the elimination/loss of drug from the anterior chamber. It has been reported that the mean half-life of [ 14 C]ketorolac in the anterior chamber after intracameral injection to rabbits with intact corneas was 2.1 h. 22 In this study, the mean halflives of ketorolac in aqueous humor after ophthalmic administration to rabbits with de-epithelialized corneas were much shorter (0.594-0.746 h).…”

Section: Figure 1seffectmentioning

confidence: 90%

See 1 more Smart Citation

Effect of Benzalkonium Chloride/EDTA on the Ocular Bioavailability of Ketorolac Tromethamine following Ocular Instillation to Normal and De-epithelialized Corneas of Rabbits

Madhu¹,

Rix²,

Shackleton³

et al. 1996

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formulations was measured in flow-through perfusion chambers. For in vivo studies, a 35 microL dose of 0.5% ketorolac tromethamine with or without BAK/EDTA was instilled into rabbit eyes with intact or de-epithelialized corneas. At 0.5, 1, 2, 4, 6, and 8 h postdose, rabbits were euthanized, and the corneas and aqueous humor were collected from both eyes. The ketorolac concentrations from both in vivo and in vitro samples were quantified by reversed-phase high-performance liquid chromatography. The in vitro study results indicated that BAK/EDTA statistically significantly increased the Focular of ketorolac through de-epithelialized corneas but not through intact corneas. The in vivo study results showed that BAK/EDTA had no effect on the Focular of ketorolac in rabbits with intact corneas, based on the values of the area under the aqueous humor concentration versus time curves (AUC0-6h) of ketorolac. As expected, de-epithelialization of the corneas produced a faster and greater ocular absorption of ketorolac as evidenced by the smaller Tmax and larger AUC values compared to those for the intact corneas in vivo. However, BAK/EDTA decreased the ocular absorption of ketorolac in rabbits with de-epithelialized corneas. The half-lives (t 1/2) of ketorolac in corneal tissue and aqueous humor were longer in rabbits with intact corneas than those in rabbits with de-epithelialized corneas. In conclusion, the in vivo Focular of ketorolac was not altered by BAK/EDTA in rabbits with intact corneas, but it was decreased by BAK/EDTA in rabbits with de-epithelialized corneas. Therefore, the formulation with ketorolac alone may be better as a post-operative ocular analgesic.

show abstract

Section: Figure 1seffectsupporting

confidence: 81%

Section: Figure 1seffectmentioning

confidence: 90%

Effect of Benzalkonium Chloride/EDTA on the Ocular Bioavailability of Ketorolac Tromethamine following Ocular Instillation to Normal and De-epithelialized Corneas of Rabbits

Madhu¹,

Rix²,

Shackleton³

et al. 1996

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Permeation studies with ketorolac and pilocarpine have revealed that corneal epithelium acts as a reservoir for drug accumulation and continuous delivery of drug to aqueous humor. [10][11][12] Thus, in the permeation study, only the drug present in the epithelium would be able to partition through the stroma and endothelium to the receptor. Increase in drug concentration in donor does not result in proportionate increase in amount of drug permeated ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas

Pawar

Majumdar

2006

AAPS PharmSciTech

View full text Add to dashboard Cite

The purpose of this investigation was to evaluate the effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drop through freshly excised goat, sheep, and buffalo corneas. Aqueous isotonic ophthalmic solutions of moxifloxacin hydrochloride of different concentrations (pH 7.2) or 0.5% (wt/vol) solutions of different pH or 0.5% solutions (pH 7.2) containing different preservatives were made. Permeation characteristics of drug were evaluated by putting 1 mL formulation on freshly excised cornea (0.50 cm 2 ) fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated in the receptor (containing 10 mL bicarbonate ringer at 37°C under stirring) by spectrophotometry at 291 nm, after 120 minutes. Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett's test. Increase in drug concentration in the formulation resulted in an increase in the quantity permeated but a decrease in percentage permeation. Increase in pH of the solution from 5.5 to 7.2 increased drug permeation, indicating pH-dependent transport. Compared with control formulation, moxifloxacin 0.5% (wt/vol) solution (pH 7.2) containing disodium edetate (EDTA) (0.01% wt/vol) produced significantly (P G .05) higher permeation with all the corneas. Formulation with benzyl alcohol significantly (P G .05) increased permeation with buffalo cornea compared with its control. Presence of benzalkonium chloride (BAK) (0.01% wt/vol) and EDTA (0.01% wt/vol) in the formulation increased permeation to the maximum with all the corneas. The results suggest that moxifloxacin 0.5% ophthalmic solution (pH 7.2) containing BAK (0.01%) and EDTA (0.01%) provides increased in vitro ocular availability through goat, sheep, and buffalo corneas.

show abstract

“…The drug concentrations in the aqueous humour were compared after topical application with those obtained after intracameral injection of an equivalent dose of 0.25 mg of ketorolac tromethamine per eye using 14C (Ling & Combas, 1987;Walters et al, 2007). Such factors have prompted research for the development of a more safe and effective KT formulations (Schoenwald, 1985;Sinha et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Fathalla

Vangala

Longman

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

129

View full text Add to dashboard Cite

, Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies, European Journal of Pharmaceutics and Biopharmaceutics (2017), doi: http://dx.doi.org/10. 1016/j.ejpb.2017.01.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThis study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (T sol-gel ), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used.P188 modified the T sol/gel of P407 bringing it close to eye temperature (35 o C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12 h. In addition, the HET-CAM and BCOP tests confirmed the nonirritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.

show abstract

Ocular Bioavailability and Tissue Distribution of [14C]Ketorolac Tromethamine in Rabbits

Cited by 42 publications

References 15 publications

Effect of Benzalkonium Chloride/EDTA on the Ocular Bioavailability of Ketorolac Tromethamine following Ocular Instillation to Normal and De-epithelialized Corneas of Rabbits

Effect of Benzalkonium Chloride/EDTA on the Ocular Bioavailability of Ketorolac Tromethamine following Ocular Instillation to Normal and De-epithelialized Corneas of Rabbits

Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Contact Info

Product

Resources

About