Mechanistic Studies on Transcorneal Permeation of Pilocarpine

Sieg, James W.; Robinson, Joseph R.

doi:10.1002/jps.2600651230

Cited by 138 publications

(35 citation statements)

References 21 publications

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“…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

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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.

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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

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“…The epithelial water is probably not accessible to lipid-insoluble drugs, but when they are lipid-soluble, as in the case of pilocarpine (SIEG and ROBINSON 1976), they can enter the cell layer, which becomes an alternative reservoir. The high concentration of such drugs suggests they are not restricted to the lipid membranes but are also dissolved in the cytosol; their distribution and dynamics have been little investigated, however.…”

Section: B) Compartmentsmentioning

confidence: 98%

Ocular Pharmacokinetics

Maurice¹,

Mishima²

1984

Handbook of Experimental Pharmacology

224

169

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“…The prednisolone concentration in whole cornea samples resulted in a measure of the total amount of the drug, without any information on the various cellular layers. The corneal epithelium has been reported to act as a penetration barrier for pilocarpine [7,11], resulting in the biphasic nature of the elimination of this drug from the whole cor nea.…”

Section: Corneal Epithelium and Stromaendothelium Concentration-time mentioning

confidence: 99%

“…The accepted mechanisms [11] for drug absorption into ocular tissues and fluids af ter subconjunctival injection are; (1) that the drug effluxes out of the puncture hole pro duced in the conjunctiva by injection, mixes with tears, and is absorbed across the cornea and/or (2) that the drug permeates directly through the conjunctiva, followed by corneal absorption.…”

Section: Ocular Tissue and Fluid Levels O F Prednisolone After Subconmentioning

confidence: 99%

Intraocular Penetration Kinetics of Prednisolone after Subconjunctival Injection in Rabbits

Tsuji¹,

Tamai²,

Sasaki³

1988

Ophthalmic Res

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Prednisolone concentrations in cornea, aqueous humor, and vitreous humor and the residual amount in conjunctival tissue were assayed by high-performance liquid chromatography during a 14-hour period after subconjunctival injection of prednisolone sodium succinate in rabbits. Prednisolone was concentrated in the corneal epithelium and reached a peak within 5 min, whereas the peak level of prednisolone in stroma-endothelium was achieved 1 h after the injection. There was an apparent linear binding of prednisolone with the ocular tissue homogenates and fluids except for the vitreous humor. However, the protein binding of prednisolone with vitreous humor showed marked concentration dependency. A pharmacokinetic model involving a rapid conversion to prednisolone from its ester prodrug, first-order transfer to various tissues, and first-order elimination of unbound prednisolone from vitreous humor succeeded in predicting the observed concentration-time profiles of prednisolone in various ocular tissues and fluids after subconjunctival injection at three different doses: 0.1, 1.0, and 10.0 mg/kg. The present model predicted that absorption into precorneal area and epithelium and direct penetration into aqueous humor and vitreous humor are 1.7, 0.1, and 0.2% of the applied dose, respectively, and that almost the entire dose (98%) is absorbed into the systemic circulation, with a half-life of 38 min.

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Mechanistic Studies on Transcorneal Permeation of Pilocarpine

Cited by 138 publications

References 21 publications

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

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

Ocular Pharmacokinetics

Intraocular Penetration Kinetics of Prednisolone after Subconjunctival Injection in Rabbits

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