Development of a non-settling gel formulation of 0.5% loteprednol etabonate for anti-inflammatory use as an ophthalmic drop

Clinical Ophthalmology

Volumn 7, Issue , 2013, Pages 299-312

  Coffey, Martin J ^a   Decory, Heleen H ^a   Lane, Stephen S ^b  

^a BAUSCH AND LOMB   (United States)

^b Associated Eye Care   (United States)

Author keywords

Clinical trial; Drug delivery; Gel; Loteprednol etabonate; Ocular surface

Indexed keywords

DEXAMETHASONE; EYE DROPS; FLUOROMETHOLONE; LOTEPREDNOL ETABONATE; PREDNISOLONE;

ABNORMAL SENSATION; BLURRED VISION; CLINICAL PRACTICE; CONCENTRATION (PARAMETERS); DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG FORMULATION; DRUG METABOLISM; DRUG PENETRATION; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; EYELID REFLEX; GIANT PAPILLARY CONJUNCTIVITIS; HUMAN; INTRAOCULAR HYPERTENSION; IRIDOCYCLITIS; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OUTCOME ASSESSMENT; PH MEASUREMENT; PHYSICAL CHEMISTRY; POSTOPERATIVE INFLAMMATION; POSTOPERATIVE PAIN; PROCESS DEVELOPMENT; RABBIT; REVIEW; SEASONAL ALLERGIC CONJUNCTIVITIS; TREATMENT CONTRAINDICATION; VISCOSITY;

EID: 84874802523     PISSN: 11775467     EISSN: 11775483     Source Type: Journal    
DOI: 10.2147/OPTH.S40588     Document Type: Review

References (68)

1. Gessi S, Merighi S, Borea PA. Glucocorticoid's pharmacology: past, present and future. Curr Pharm Des. 2010;16:3540-3553.
2. Stahn CB, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4(10):525-533.
3. Cidlowski JA. Glucocorticoids and their actions in cells. Retina. 2009;29(6):S21-S23.
4. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.
5. Stahn C, Löwenberg M, Hommes DW, Buttgereit F. Molecular mecha-nisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol. 2007;275(1-2):71-78.
6. Ananthula HK, Vaishya RD, Barot M, Mitra AK. Bioavailability. In: Tasman W, Jaeger EA, editors. Duane's Ophthalmology. Philadelphia: Lippincott Williams and Wilkins; 2011.
7. Rupenthal ID, Alany RG. Ocular drug delivery. In: Gad SC, editor. Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development and Manufacturing. John Wiley and Sons, Inc; 2010:1-39. Published online March 15, 2010; doi 10.1002/9780470571224. Accessed October 19, 2012.
8. Mishima S, Gasset A, Klyce SD, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5(3):264-276.
9. Tomlinson A, Khanal S. Assessment of tear film dynamics: quantification approach. Ocul Surf. 2005;3(2):81-95.
10. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348-360.
11. Van Ooteghem MM. Factors influencing the retention of ophthalmic solutions on the eye surface. In: Saettone MS, Bucci M, Speiser P, editors. Ophthalmic Drug Delivery: Biopharmaceutical, Technological and Clinical Aspects. Fidia Research Series. Padova, Italy: Liviana Press; 1987;11:7-17.
12. Conrad JM, Reay WA, Polcyn RE, Robinson JR. Influence of tonicity and pH on lacrimation and ocular drug bioavailability. J Parenteral Drug Assoc. 1978;32(4):149-161.
13. Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Del Rev. 2005;57:1595-1639.
14. Bron AJ, Tiffany JM. The meibomian glands and tear film lipids: structure, function, and control. In: Sullivan DA, Dartt DA, Meneray MM. Lacrimal Gland, Tear Film, and Dry Eye Syndromes 2: Basic Science and Clinical Relevance. New York: Plenum Press; 1998:281-295.
15. Gilbard JP. Human tear film electrolyte concentrations in health and dry-eye disease. Proceedings of the Annual Meeting of the Association for Research and Vision in Ophthalmology; May 3-8, 1992; Sarasota, FL.
16. Lentner C, editor. Geigy Scientific Tables: Units of Measurement, Body Fluids, Composition of the Body, and Nutrition. Basel: Ciba Pharmaceutical Co; 1981:178-184.
17. Zhang W, Prausnitz MR, Edwards A. Model of transient drug diffusion across cornea. J Control Release. 2004;99(2):241-258.
18. Huang H-S, Schoenwald RD, Lach JL. Corneal penetration of beta-blocking agents II: assessment of barrier contribution. J Pharm Sci. 1983;72:1272-1279.
19. Watsky MA, Jablonski MM, Edelhauser HF. Comparison of conjunctival and corneal surface areas in rabbit and human. Curr Eye Res. 1988;7(5):483-486.
20. Kim SH, Lutz RJ, Wang NS, Robinson MR. Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic Res. 2007;39(5):244-254.
21. Bodor N, Loftsson T, Wu W-M. Metabolism, distribution, and transdermal permeation of a soft corticosteroid, loteprednol etabonate. Pharm Res. 1992;9(10):1275-1278.
22. Bodor N, Buchwald P. Soft drug design: general principles and recent applications. Med Res Rev. 2000;20(1):58-101.
23. McGhee CNJ, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25(1):33-55.
24. Clark AF, Steely HT, Dickerson JE Jr, et al. Glucocorticoid induction of the glaucoma gene MYOC in human and monkey trabecular meshwork cells and tissues. Invest Ophthalmol Vis Sci. 2001;42(8):1769-1780.
25. Clark AF, Wordinger RJ. The role of steroids in outflow resistance. Exp Eye Res. 2009;88:752-759.
26. Manabe S, Bucala R, Cerami A. Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts. J Clin Invest. 1984;74(5):1803-1810.
27. Alberth M, Wu W-M, Winwood D, Bodor N. Lipophilicity, solubility, and permeability of loteprednol etabonate: a novel, soft, anti-inflammatory steroid. J Biopharm Sci. 1991;2(2):115-125.
28. Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprendol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991;10(10):933-937.
29. Glogowski S, Proksch JW. Ocular pharmacokinetics of loteprednol etabonate following ocular administration of a novel ointment formulation or a suspension (Lotemax®) in rabbits with corneal inflammation. Proceedings of the Annual Meeting of the Association for Research and Vision in Ophthalmology; May 2-6, 2010; Fort Lauderdale, FL.
30. Druzgala P, Hochhaus G, Bodor N. Soft drugs-10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol. 1991;38(2):149-154.
31. Dell SJ, Lowry GM, Northcutt JA, Howes J, Novack GD, Hart K. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol. 1998;102(2):251-255.
32. Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Loteprednol Etabonate US Uveitis Study Group. Am J Ophthalmol. 1999;127(5):537-544.
33. Shulman DG, Lothringer LL, Rubin JM, et al. A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis. Ophthalmology. 1999;106(2):362-369.
34. Ilyas H, Slonim CB, Braswell GR, Favetta JR, Schulman M. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye Contact Lens. 2004;30(1):10-13.
35. Friedlaender MH, Howes J. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. The Loteprednol Etabonate Giant Papillary Conjunctivitis Study Group I. Am J Ophthalmol. 1997;123(4):455-464.
36. Stewart R, Horwitz B, Howes J, Novack GD, Hart K. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1. J Cataract Refract Surg. 1998; 24(11):1480-1489.
37. A double-masked, placebo-controlled evaluation of 0.5% loteprednol etabonate in the treatment of postoperative inflammation. The Loteprednol Etabonate Postoperative Inflammation Study Group 2. Ophthalmology. 1998;105(9):1780-1786.
38. Comstock TL, Paterno MR, Singh A, Erb T, Davis E. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011;5:177-186.
39. Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocu-lar pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998;7(4):266-269.
40. Comstock TL, DeCory HH. Advances in corticosteroid therapy for ocular inflammation: loteprendol etabonate. Int J Inflam. 2012;2012:789623.doi: 10.1155/2012/789623.
41. Bartlett JD, Horwitz B, Laibovitz R, Howes JF. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993;9(2):157-165.
42. Holland EJ, Bartlett JD, Paterno MR, Usner DW, Comstock TL. Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intra-o cular pressure in healthy volunteers. Cornea. 2008;27(1):50-55.
43. Holland EJ, Djalilian AR, Sanderson JP. Attenuation of ocular hypertension with the use of topical loteprednol etabonate 0.5% in steroid responders after corneal transplantation. Cornea. 2009;28(10):1139-1143.
44. Chen M, Gong L, Sun X, et al. A multicenter, randomized, parallel-group clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin. 2012;28(3):1-10.
45. Amon M, Busin M. Loteprednol etabonate ophthalmic suspension 0.5%: efficacy and safety for postoperative anti-inflammatory use. Int Ophthalmol. 2012;32(5):507-517.
46. CFR-Code of Federal Regulations Title 21. Part 349.12 Ophthalmic demulcents, and Part 349.60 Labeling of ophthalmic demulcent drug products. Revised April 1, 2012. Available from: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CF RPart=349. Accessed November 12, 2012.
47. Apt L, Henrick A, Silverman LM. Patient compliance with use of topical ophthalmic corticosteroid suspensions. Am J Ophthalmol. 1979;87(2):210-214.
48. Fiscella RG. Ophthalmic drug formulations. In: Bartlett JD, Jaanus SD, editors. Clinical Ocular Pharmacology, 5th ed. St Louis, MO: Butterworth-Heinemann; 2008.
49. Coffey MJ, Davio SR. Viscoelastic and sedimentation characterization of loteprednol etabonate ophthalmic gel, 0.5%. Proceedings of the Annual Meeting of the Association for Research and Vision in Ophthalmology; May 10, 2012; Fort Lauderdale, FL.
50. Piau JM. Carbopol gels: elastoviscoplastic and slippery glasses made of individual swollen sponges. Meso-and macroscopic properties, constitutive equations and scaling laws. J Nonnewton Fluid Mech. 2007;144:1-29.
51. Kaur IP, Lal S, Rana C, Kakkar S, Singh H. Ocular perservatives: associated risks and newer options. Cutan Ocul Toxicol. 2009;28(3): 93-103.
52. Epstein SP, Ahdoot M, Marcus E, Asbell PA. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009;25(2):113-119.
53. United States Pharmacopoeia (USP 35-NF 30). The United States Pharmacopeia Convention: United States Pharmacopeia/National Formulary. Rockville, MD: US Pharmacopeia; 2012.
54. Ykuji Nippo Ltd: Japanese Pharmacopoeia, 15th ed. Tokyo: Maruzen Co, Ltd; 2006.
55. European Pharmacopoeia, 7th ed. 2012 (7.5). European Directorate for the Quality of Medicines and Health Care: efficacy of antimicrobial preservation. Strasbourg: European Directorate for the Quality of Medicines; 2006:5129-5130.
56. Hu Z, Denick J, inventors; Bausch and Lomb Incorporated, assignee. Ophthalmic compositions including glycerin and propylene glycol. United States patent US 5800807. September 1, 1998.
57. Glogowski S, Jiang S. Ocular and systemic pharmacokinetics of loteprednol etabonate gel (0.5%) following topical ocular administration to rabbits. Paper presented at: Annual Meeting of the Association for Research and Vision in Ophthalmology; May 6-10, 2012. Fort Lauderdale, FL.
58. Chrai SS, Patton TF, Mehta A, Robinson JR. Lacrimal and instilled fluid dynamics in rabbit eyes. J Pharm Sci. 1973;62(7):1112-1121.
59. Saettone MF, Giannaccini B, Barattini F, Tellini N. The validity of rab-bits for investigations on ophthalmic vehicles: a comparison of four different vehicles containing tropicamide in humans and rabbits. Pharm Acta Helv. 1982;57(2):47-55.
60. Zaki I, Fitzgerald P, Hardy JG, Wilson CG. A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man. J Pharm Pharmacol. 1986;38(6):463-466.
61. Rajpal RK, Roel L, Siou-Mermet R, Erb T. Evaluation of the efficacy and safety of loteprednol etabonate gel 0.5% in the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. In press 2012.
62. Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5% for postoperative pain and inflammation after cataract surgery: results of a multicenter trial. Clin Ophthalmol. 2012;6: 1113-1124.
63. El-Harazi SM, Feldman RM. Control of intra-ocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2001; 12(1):4-8.
64. Mohammadpour M, Jafarinasab MR, Javadi MA. Outcomes of acute postoperative inflammation after cataract surgery. Eur J Ophthalmol. 2007;17(1):20-28.
65. Wittpenn JR, Silverstein S, Heier J, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008;146(4): 554-560.
66. Parekh JG, Newsom TH, Nielsen S. Safety of besifloxacin ophthalmic suspension 0.6% in cataract surgery patients. J Cataract Refract Surg. 2012;38(10):1864-1867.
67. Raizman MB, Donnenfeld ED, Weinstein AJ. Clinical comparison of two topical prednisolone acetate 1% formulations in reducing inflammation after cataract surgery. Curr Med Res Opin. 2007;23(10): 2325-2331.
68. Lane SS, Holland EJ. A randomized, multicenter, masked evaluation of 0.5% loteprednol etabonate versus 1.0% prednisolone acetate for the treatment of inflammation following cataract surgery. J Cataract Refract Surg. In press 2012.