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. 2006 Feb 10;7(1):E89. doi: 10.1208/pt070113

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

Pravin Kondiba Pawar 1,✉, Dipak K Majumdar 1,✉
PMCID: PMC2750720  PMID: 16584143

Abstract

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 cm2) 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<.05) higher permeation with all the corneas. Formulation with benzyl alcohol significantly (P<.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.

Keywords: moxifloxacin, concentration, pH, preservative, cornea, permeation

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Footnotes

Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi-110017, India

References

  • 1.Hardman JG, Limbird LE. Goodman & Gillman’s The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill; 2001. [Google Scholar]
  • 2.Biedenbach DJ, Jones RN. The comparative antimicrobial activity of levofloxacin tested against 350 clinical isolates of Streptococci. Diagn Microbiol Infect Dis. 1996;25:47–51. doi: 10.1016/0732-8893(96)00066-1. [DOI] [PubMed] [Google Scholar]
  • 3.Dalhoff A, Petersen U, Endermann R. In vitro activity of Bay 12-8039, a new 8-methoxyquinolone. Chemotherapy. 1996;42:410–425. doi: 10.1159/000239474. [DOI] [PubMed] [Google Scholar]
  • 4.Davis R, Bryson HM. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994;47:677–700. doi: 10.2165/00003495-199447040-00008. [DOI] [PubMed] [Google Scholar]
  • 5.Kowalski RP, Dhaliwal DK, Karenchak LM, et al. Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin and ofloxacin using bacterial keratitis isolates. Am J Ophthalmol. 2003;136:500–505. doi: 10.1016/S0002-9394(03)00294-0. [DOI] [PubMed] [Google Scholar]
  • 6.Dajcs JJ, Thibodeaux BA, Marquart ME, Girgis DO, Traiedj M, O’Callaghan RJ. Effectiveness of ciprofloxacin, levofloxacin or moxifloxacin for treatment of experimental Staphylococcus aureus keratitis. Antimicrob Agents Chemother. 2004;48:1948–1952. doi: 10.1128/AAC.48.6.1948-1952.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Mather R, Stewart JM, Tisha P, Wong J, Stephen DM. The effect of cataract surgery on ocular levels of topical moxifloxacin. Am J Ophthalmol. 2004;138:554–559. doi: 10.1016/j.ajo.2004.05.011. [DOI] [PubMed] [Google Scholar]
  • 8.Kowalski RP, Romanowski EG, Mah FS, Yates KA, Gordon YJ. Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. Am J Ophthalmol. 2004;138:33–37. doi: 10.1016/j.ajo.2004.02.051. [DOI] [PubMed] [Google Scholar]
  • 9.Malhotra M, Majumdar DK. In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops. Indian J Exp Biol. 1997;35:941–947. [PubMed] [Google Scholar]
  • 10.Ling TL, Combs DL. Ocular bioavailability and tissue distribution [14C] ketorolac tromethamine in rabbits. J Pharm Sci. 1987;76:289–294. doi: 10.1002/jps.2600760405. [DOI] [PubMed] [Google Scholar]
  • 11.Sieg JW, Robinson JR. Mechanistic studies on transcorneal permeation of pilocarpine. J Pharm Sci. 1976;65:1816–1822. doi: 10.1002/jps.2600651230. [DOI] [PubMed] [Google Scholar]
  • 12.Madhu C, Rix PJ, Shackleton MJ, Nguyen TG, Tang Liu DDS. Effect of benzalkonium, chloride/EDTA on the ocular bioavailability of ketorolac tromethamine following ocular instillations to normal and deepithelialized corneas of rabbits. J Pharm Sci. 1996;85:415–418. doi: 10.1021/js9504189. [DOI] [PubMed] [Google Scholar]
  • 13.Gupta M, Majumdar DK. Effect of concentration, pH and preservative on in vitro transcorneal permeation of ibuprofen and flurbiprofen from buffered and nonbuffered aqueous drops. Indian J Exp Biol. 1997;35:844–849. [PubMed] [Google Scholar]
  • 14.Richman JB, Tang-Liu DD. A corneal perfusion device for estimating ocular bioavailability in vitro. J Pharm Sci. 1990;79:153–157. doi: 10.1002/jps.2600790215. [DOI] [PubMed] [Google Scholar]
  • 15.Maurice DM, Riley MV. Ocular Pharmacokinetics. In: Graymore CN, editor. Biochemistry of the Eye. London, UK: Academic Press; 1970. pp. 6–16. [Google Scholar]
  • 16.Rojanasakul Y, Robinson JR. Transport mechanisms of the cornea: characterization of barrier permselectivity. Int J Pharm. 1989;55:237–246. doi: 10.1016/0378-5173(89)90047-1. [DOI] [Google Scholar]
  • 17.Kawazu K, Midori Y, Shiono H, Ota A. Characterization of the carrier-mediated transport of levofloxacin, a fluoroquionolone antimicrobial agent, in rabbit cornea. J Pharm Pharmacol. 1999;51:797–801. doi: 10.1211/0022357991773168. [DOI] [PubMed] [Google Scholar]
  • 18.Grass GM, Wood RW, Robinson JR. Effects of calcium chelating agents on corneal permeability. Invest Ophthalmol Vis Sci. 1985;26:110–113. [PubMed] [Google Scholar]
  • 19.Ashton P, Diepold R, Platzer A, Lee VH. The effect of chlorhexidine acetate on the corneal penetration of sorbitol from an arnolol formulation in the albino rabbit. J Ocul Pharmacol. 1990;6:37–47. doi: 10.1089/jop.1990.6.37. [DOI] [PubMed] [Google Scholar]
  • 20.Rojanasakul Y, Liaw J, Robinson JR. Mechanism of action of some penetration enhancers in the cornea: laser scanning confocal microscopic and electrophysiology studies. Int J Pharm. 1990;66:131–142. doi: 10.1016/0378-5173(90)90392-H. [DOI] [Google Scholar]
  • 21.Schoenwald RD, Huang HS. Corneal penetration behavior of beta-blocking agents. I. physicochemical factors. J Pharm Sci. 1983;72:1266–1272. doi: 10.1002/jps.2600721108. [DOI] [PubMed] [Google Scholar]
  • 22.Hecht G, Roehrs RE, Cooper ER, Hiddeman JW, Van Duzee BF. Evaluation of Ophthalmic Pharmaceutical Products. In: Banker GS, Rhodes CT, editors. Modern, Pharmaceutics. New York, NY: Marcel Dekker; 1990. pp. 539–603. [Google Scholar]

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