• MIRA DESAI Department of Pharmacology, Nootan Medical College and Research Centre, Visnagar, Gujarat, India.
  • JIGAR KAPADIA Department of Pharmacology, B. J. Medical College, Ahmedabad, Gujarat, India. https://orcid.org/0000-0002-1039-2621




Bioavailability, Intraocular, Drugs


Ophthalmic drug delivery remains a significant challenge to the clinicians. A number of anatomic and physiological barriers restrict the entry of drug inside the ocular tissues, especially in the posterior segment of eye. The present review discusses various ocular barriers and drug factors which influence the ophthalmic drug delivery. Furthermore, recent advances in ophthalmic drug formulations attempted to overcome these barriers have been explored.


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Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brother Medical Publishers; 2014. p. 16.

Satoskar RS, Rege NN, Bhandarkar SD. Pharmacology and Pharmacotherapeutics. 24th ed. Haryana: Elsevier; 2015. p. 12.

Kompella UB, Kadam RS, Lee VH. Recent advances in ophthalmic drug delivery. Ther Deliv 2010;1:435-56. doi: 10.4155/TDE.10.40, PMID 21399724.

Chan J, El Maghraby GM, Craig JP, Alany RG. Phase transition water-in-oil microemulsions as ocular drug delivery systems: In vitro and in vivo evaluation. Int J Pharm 2007;328:65-71. doi: 10.1016/j. ijpharm.2006.10.004, PMID 17092668.

Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J 2010;12:348-60. doi: 10.1208/s12248-010-9183-3, PMID 20437123.

Joseph M, Trinh HM, Cholkar K, Pal D, Mitra AK. Recent perspectives on the delivery of biologics to back of the eye. Expert Opin Drug Deliv 2017;14:631-45. doi: 10.1080/17425247.2016.1227783, PMID 27573097.

Rabinovich-Guilatt L, Couvreur P, Lambert G, Dubernet C. Cationic vectors in ocular drug delivery. J Drug Target 2004;12:623-33. doi: 10.1080/10611860400015910, PMID 15621688.

Malhotra M, Majumdar DK. Permeation through cornea. Indian J Exp Biol 2001;39:11-24. PMID 11349520.

Manish K, Kulkarni GT. Recent advances in ophthalmic drug delivery system. Int J Pharm Pharm Sci 2012;4:387-94.

Ruponen M, Urtti A. Undefined role of mucus as a barrier in ocular drug delivery. Eur J Pharm Biopharm 2015;96:442-6. doi: 10.1016/j. ejpb.2015.02.032, PMID 25770770.

Benedetto DA, Shah DO, Kaufman HE. The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film. Invest Ophthalmol 1975;14:887-902. PMID 1104516.

Jünemann AG, Chorągiewicz T, Ozimek M, Grieb P, Rejdak R. Drug bioavailability from topically applied ocular drops. Does drop size matter? Ophthalmol J 2016;1:29-35. doi: 10.5603/OJ.2016.0005.

Saettone MF. Progress and problems in ophthalmic drug delivery. Bus Brief Pharmtech 2002;1:167-71.

Kumar A, Malviya R, Sharma PK. Recent trends in ocular drug delivery: A short review. Eur J Appl Sci 2011;3:86-92.

Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today 2008;13:135-43. doi: 10.1016/j.drudis.2007.11.002, PMID 18275911.

Lee YH, Kompella UB, Lee VH. Systemic absorption pathways of topically applied beta adrenergic antagonists in the pigmented rabbit. Exp Eye Res 1993;57:341-9. doi: 10.1006/exer.1993.1133, PMID 7901046.

Barar J, Asadi M, Mortazavi-Tabatabaei SA, Omidi Y. Ocular drug delivery; impact of in vitro cell culture models. J Ophthalmic Vis Res 2009;4:238-52. PMID 23198080.

Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 2006;58:1131-5. doi: 10.1016/j. addr.2006.07.027, PMID 17097758.

Ahmed I, Patton TF. Importance of the noncorneal absorption route in topical ophthalmic drug delivery. Invest Ophthalmol Vis Sci 1985;26:584-7. PMID 3884542.

Kim H, Robinson MR, Lizak MJ, Tansey G, Lutz RJ, Yuan P, et al. Controlled drug release from an ocular implant: An evaluation using dynamic three-dimensional magnetic resonance imaging. Invest Ophthalmol Vis Sci 2004;45:2722-31. doi: 10.1167/iovs.04-0091, PMID 15277497.

Robinson MR, Lee SS, Kim H, Kim S, Lutz RJ, Galban C, et al. A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide. Exp Eye Res 2006;82:479-87. doi: 10.1016/j. exer.2005.08.007, PMID 16168412.

Ghate D, Brooks W, McCarey BE, Edelhauser HF. Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry. Invest Ophthalmol Vis Sci 2007;48:2230-7. doi: 10.1167/iovs.06-0954, PMID 17460284.

Srirangam R, Majumdar S. Transscleral Drug Delivery to the Posterior Segment of the Eye: Particulate and Colloidal Formulations and Biopharmaceutical Considerations. In: Advances in Ocular Drug Delivery. Kerala, India: Research Signpost; 2012.

Rada JA, Shelton S, Norton TT. The sclera and myopia. Exp Eye Res 2006;82:185-200. doi: 10.1016/j.exer.2005.08.009, PMID 16202407.

Ambati J, Canakis CS, Miller JW, Gragoudas ES, Edwards A, Weissgold DJ, et al. Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci 2000;41:1181-5. PMID 10752958.

Kim YC, Chiang B, Wu X, Prausnitz MR. Ocular delivery of macromolecules. J Control Release 2014;190:172-81. doi: 10.1016/j. jconrel.2014.06.043, PMID 24998941.

Olsen TW, Edelhauser HF, Lim JI, Geroski DH. Human scleral permeability. Effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci 1995;36:1893-903. PMID 7543465.

Pitkänen L, Ranta VP, Moilanen H, Urtti A. Permeability of retinal pigment epithelium: Effects of permeant molecular weight and lipophilicity. Invest Ophthalmol Vis Sci 2005;46:641-6. doi: 10.1167/ iovs.04-1051, PMID 15671294.

Edelhauser HF, Rowe-Rendleman CL, Robinson MR, Dawson DG, Chader GJ, Grossniklaus HE, et al. Ophthalmic drug delivery systems for the treatment of retinal diseases: Basic research to clinical

applications. Invest Ophthalmol Vis Sci 2010;51:5403-20. doi: 10.1167/ iovs.10-5392, PMID 20980702.

Dalkara D, Kolstad KD, Caporale N, Visel M, Klimczak RR, Schaffer DV, et al. Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous. Mol Ther 2009;17:2096-102. doi: 10.1038/mt.2009.181, PMID 19672248.

Jackson TL, Antcliff RJ, Hillenkamp J, Marshall J. Human retinal molecular weight exclusion limit and estimate of species variation. Invest Ophthalmol Vis Sci 2003;44:2141-6. doi: 10.1167/iovs.02-1027, PMID 12714654.

Ursell PG, Spalton DJ, Whitcup SM, Nussenblatt RB. Cystoid macular edema after phacoemulsification: Relationship to blood-aqueous barrier damage and visual acuity. J Cataract Refract Surg 1999;25:1492-7. doi: 10.1016/s0886-3350(99)00196-0, PMID 10569164.

Bellhorn RW. Permeability of blood-ocular barriers of neonatal and adult cats to fluorescein-labeled dextrans of selected molecular sizes. Invest Ophthalmol Vis Sci 1981;21:282-90. PMID 6166586.

Coburn PS, Wiskur BJ, Astley RA, Callegan MC. Blood-retinal barrier compromise and endogenous Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 2015;56:7303-11. doi: 10.1167/ iovs.15-17488, PMID 26559476.

Cheruvu NP, Amrite AC, Kompella UB. Effect of diabetes on transscleral delivery of celecoxib. Pharm Res 2009;26:404-14. doi: 10.1007/s11095-008-9757-2, PMID 18987961.

Barot M, Bagui M, Gokulgandhi MR, Mitra AK. Prodrug strategies in ocular drug delivery. Med Chem 2012;8:753-68. doi: 10.2174/157340612801216283, PMID 22530907.

Ramsay E, Del Amo EM, Toropainen E, Tengvall-Unadike U, Ranta VP, Urtti A, et al. Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye. Eur J Pharm Sci 2018;119:83-9. doi: 10.1016/j.ejps.2018.03.034, PMID 29625211.

Chrai SS, Robinson JR. Ocular evaluation of methylcellulose vehicle in albino rabbits. J Pharm Sci 1974;63:1218-23. doi: 10.1002/ jps.2600630810, PMID 4853424.

Loftsson T, Masson M. Cyclodextrins in topical drug formulations: Theory and practice. Int J Pharm 2001;225:15-30. doi: 10.1016/s0378- 5173(01)00761-x, PMID 11489551.

Baranowski P, Karolewicz B, Gajda M, Pluta J. Ophthalmic drug dosage forms: Characterisation and research methods. Sci World J 2014;2014:861904. doi: 10.1155/2014/861904, PMID 24772038.

Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm. 2012;81:463-9. doi: 10.1016/j. ejpb.2012.04.007, PMID 22561955.

Pitkänen L, Ruponen M, Nieminen J, Urtti A. Vitreous is a barrier in nonviral gene transfer by cationic lipids and polymers. Pharm Res 2003;20:576-83. doi: 10.1023/a:1023238530504, PMID 12739764.

Pitkänen L, Ranta VP, Moilanen H, Urtti A. Binding of betaxolol, metoprolol and oligonucleotides to synthetic and bovine ocular melanin, and prediction of drug binding to melanin in human choroid-retinal pigment epithelium. Pharm Res 2007;24:2063-70. doi: 10.1007/ s11095-007-9342-0, PMID 17546409.

Al-Ghananeem AM, Crooks PA. Phase I and phase II ocular metabolic activities and the role of metabolism in ophthalmic prodrug and codrug design and delivery. Molecules 2007;12:373-88. doi: 10.3390/12030373, PMID 17851396.

Sigurdsson HH, Konráethsdóttir F, Loftsson T, Stefánsson E. Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye. Acta Ophthalmol Scand 2007;85:598-602. doi: 10.1111/j.1600-0420.2007.00885.x, PMID 17645424.

Loftsson T, Hreinsdóttir D, Stefánsson E. Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: Aqueous dexamethasone eye drops. J Pharm Pharmacol 2007;59:629-35. doi: 10.1211/jpp.59.5.0002, PMID 17524227.

Inoue J, Oka M, Aoyama Y, Kobayashi S, Ueno S, Hada N, et al. Effects of dorzolamide hydrochloride on ocular tissues. J Ocul Pharmacol Ther 2004;20:1-13. doi: 10.1089/108076804772745419, PMID 15006154.

Koevary SB. Pharmacokinetics of topical ocular drug delivery: Potential uses for the treatment of diseases of the posterior segment and beyond. Curr Drug Metab 2003;4:213-22. doi: 10.2174/1389200033489488, PMID 12769666.

Acheampong AA, Shackleton M, John B, Burke J, Wheeler L, Tang- Liu D. Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes. Drug Metab Dispos 2002;30:421-9. doi: 10.1124/dmd.30.4.421, PMID 11901096.

Koeberle MJ, Hughes PM, Skellern GG, Wilson CG. Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. Pharm Res 2006;23:2781-98. doi: 10.1007/s11095-006-9106-2, PMID17103338.

Lau D, Leung L, Ferdinands M, Allen PJ, Fullinfaw RO, Davies GE, et al. Penetration of 1% voriconazole eye drops into human vitreous humour: A prospective, open-label study. Clin Exp Ophthalmol 2009;37:197-200. doi: 10.1111/j.1442-9071.2008.01911.x, PMID 19723128.

Holló G, Whitson JT, Faulkner R, McCue B, Curtis M, Wieland H, et al. Concentrations of betaxolol in ocular tissues of patients with glaucoma and normal monkeys after 1 month of topical ocular administration. Invest Ophthalmol Vis Sci 2006;47:235-40. doi: 10.1167/iovs.05-0945, PMID 16384968.

Colleaux KM, Hamilton WK. Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol 2000;35:373-8. doi: 10.1016/s0008- 4182(00)80124-6, PMID 11192445.

Suzuki T, Uno T, Chen G, Ohashi Y. Ocular distribution of intravenously administered micafungin in rabbits. J Infect Chemother 2008;14:204-7. doi: 10.1007/s10156-008-0612-5, PMID 18574655.

Regnier A, Schneider M, Concordet D, Toutain PL. Intraocular pharmacokinetics of intravenously administered marbofloxacin in rabbits with experimentally induced acute endophthalmitis. Am J Vet Res 2008;69:410-5. doi: 10.2460/ajvr.69.3.410, PMID 18312141.

Goldblum D, Rohrer K, Frueh BE, Theurillat R, Thormann W, Zimmerli S. Ocular distribution of intravenously administered lipid formulations of amphotericin B in a rabbit model. Antimicrob Agents Chemother 2002;46:3719-23. doi: 10.1128/AAC.46.12.3719- 3723.2002, PMID 12435667.

Geroski DH, Edelhauser HF. Drug delivery for posterior segment eye disease. Invest Ophthalmol Vis Sci 2000;41:961-4. PMID 10752928.

Alimera Sciences Inc. Alimera Sciences Provides Details on FDA Approval of Iluvien® as the First Long-term Treatment for Diabetic Macular Edema. Alpharetta, Georgia: Alimera Sciences Inc. Available from: http://www.investor.alimerasciences.com/releasedetail. cfm?ReleaseID=873403Last [Last accessed on 2016 Dec 18].

Grampurohit N, Ravikumar P, Mallya R. Microemulsions for topical use-a review. Ind J Pharm Educ Res 2011;45:100-7.

Ali M, Byrne ME. Challenges and solutions in topical ocular drug-delivery systems. Expert Rev Clin Pharmacol 2008;1:145-61. doi: 10.1586/17512433.1.1.145, PMID 24410518.

Hornof MD, Bernkop‐Schnürch A. In vitro evaluation of the permeation enhancing effect of polycarbophil-cysteine conjugates on the cornea of rabbits. J Pharm Sci 2002;91:2588-92. doi: 10.1002/jps.10258, PMID 12434402.

Fingeret M, Dickerson JE Jr. The role of minimally invasive glaucoma surgery devices in the management of glaucoma. Optom Vis Sci 2018;95:155-62. doi: 10.1097/OPX.0000000000001173, PMID 29370021.

Gupta S, Vyas SP. Carbopol/chitosan based pH triggered in situ gelling system for ocular delivery of timolol maleate. Sci Pharm 2010;78:959-76. doi: 10.3797/scipharm.1001-06, PMID 21179328.

HB N, Bakliwal S, Pawar S. In-situ gel: New trends in controlled and sustained drug delivery system. Int J PharmTech Res 2010;2:1398-408.

Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 2006;23:2709-28. doi: 10.1007/s11095-006-9104-4, PMID 17096184.

Miller SC, Donovan MD. Effect of poloxamer 407 gel on the miotic activity of pilocarpine nitrate in rabbits. Int J Pharm 1982;12:147-52. doi: 10.1016/0378-5173(82)90114-4.

Khiev D, Mohamed ZA, Vichare R, Paulson R, Bhatia S, Mohapatra S, et al. Emerging nano-formulations and nanomedicines applications for ocular drug delivery. Nanomaterials (Basel) 2021;11:173. doi: 10.3390/ nano11010173, PMID 33445545.

Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci 2014;103:29-52. doi: 10.1002/jps.23773, PMID 24338748.

Pleyer U, Lutz S, Jusko WJ, Nguyen KD, Narawane M, Rückert D, et al. Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye. Invest Ophthalmol Vis Sci 1993;34:2737-42. PMID 7688360.

Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA, Khan ZI. Microemulsions: A novel approach to enhanced drug delivery. Rec Pat Drug Deliv Formul 2008;2:238-57. doi: 10.2174/187221108786241679, PMID 19075911.

Mishra A, Panola R, Rana AC. Microemulsions: As drug delivery system. J Sci Innov Res 2014;3:467-74. doi: 10.31254/jsir.2014.3412.

Naveh N, Muchtar S, Benita S. Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect in rabbits. J Ocul Pharmacol Ther 2009;10:509-20.

Liang H, Baudouin C, Faure MO, Lambert G, Brignole-Baudouin F. Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: An in vivo toxicity assay. Mol Vis 2009;15:1690-9. PMID 19710954.

Jiang J, Gill HS, Ghate D, McCarey BE, Patel SR, Edelhauser HF, et al. Coated microneedles for drug delivery to the eye. Invest Ophthalmol Vis Sci 2007;48:4038-43. doi: 10.1167/iovs.07-0066, PMID 17724185.

Patane MA, Cohen AE, Sheppard JD, Nguyen QD. Ocular iontophoresis for drug delivery. Retina Today 2011;6:64-6.

Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 2012;64:1547-68. doi: 10.1016/j. addr.2012.04.005, PMID 22575858.

Jung JH, Chiang B, Grossniklaus HE, Prausnitz MR. Ocular drug delivery targeted by iontophoresis in the suprachoroidal space using a microneedle. J Control Release 2018;277:14-22. doi: 10.1016/j. jconrel.2018.03.001, PMID 29505807.



How to Cite

DESAI, M., and J. KAPADIA. “FACTORS AFFECTING INTRAOCULAR BIOAVAILABILITY OF DRUGS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 15, no. 9, Sept. 2022, pp. 15-24, doi:10.22159/ajpcr.2022.v15i9.45302.



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