Drug Delivery and Translational Research

, Volume 6, Issue 4, pp 399–413 | Cite as

Nanocrystal for ocular drug delivery: hope or hype

  • Om Prakash Sharma
  • Viral Patel
  • Tejal MehtaEmail author
Review Article


The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.


Drug nanocrystal Ocular Nanotechnology Drug delivery Bioavailability Corneal permeation Poorly soluble drugs 



Authors are also thankful to Prof. Anuradha K. Gajjar for her kind support in editing of manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Gan L, Wang J, Jiang M, Bartlett H, Ouyang D, Eperjesi F, et al. Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers. Drug Discov Today. 2013;18(5):290–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Conway BR. Recent patents on ocular drug delivery systems. Recent Pat Drug Deliv Formul. 2008;2(1):1–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Araújo J, Gonzalez E, Egea MA, Garcia ML, Souto EB. Nanomedicines for ocular NSAIDs: safety on drug delivery. Nanomedicine. 2009;5(4):394–401.PubMedGoogle Scholar
  4. 4.
    Yang X, Trinh HM, Agrahari V, Sheng Y, Pal D, Mitra AK. Nanoparticle-based topical ophthalmic gel formulation for sustained release of hydrocortisone butyrate. AAPS PharmSciTech. 2015:1–13Google Scholar
  5. 5.
    Honda M, Asai T, Oku N, Araki Y, Tanaka M, Ebihara N. Liposomes and nanotechnology in drug development: focus on ocular targets. Int J Nanomedicine. 2013;8:495–504.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gaudana R, Jwala J, Boddu SH, Mitra AK. Recent perspectives in ocular drug delivery. Pharm Res. 2009;26(5):1197–216.CrossRefPubMedGoogle Scholar
  7. 7.
    Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems: a shift to the posterior segment. Drug Discov Today. 2008;13(3):135–43.PubMedGoogle Scholar
  8. 8.
    Lang JC. Ocular drug delivery conventional ocular formulations. Adv Drug Deliv Rev. 1995;16(1):39–43.CrossRefGoogle Scholar
  9. 9.
    Achouri D, Alhanout K, Piccerelle P, Andrieu V. Recent advances in ocular drug delivery. Drug Dev Ind Pharm. 2013;39(11):1599–617.CrossRefPubMedGoogle Scholar
  10. 10.
    Kaur IP, Smitha R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm. 2002;28(4):353–69.CrossRefPubMedGoogle Scholar
  11. 11.
    Prabhu P, Dubey A, Parth V, Ghate V. Investigation of hydrogel membranes containing combination of gentamicin and dexamethasone for ocular delivery. Int J Pharm Investig. 2015;5(4):214–25.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Meisner D, Mezei M. Liposome ocular delivery systems. Adv Drug Deliv Rev. 1995;16(1):75–93.CrossRefGoogle Scholar
  13. 13.
    Abdelbary G, El-gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech. 2008;9(3):740–7.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vandamme TF. Microemulsions as ocular drug delivery systems: recent developments and future challenges. Prog Retin Eye Res. 2002;21(1):15–34.CrossRefPubMedGoogle Scholar
  15. 15.
    Kambhampati SP, Kannan RM. Dendrimer nanoparticles for ocular drug delivery. J Ocul Pharmacol Ther. 2013;29(2):151–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Barar I, Omidi Y. Nanoparticles for ocular drug delivery. Nanomedicine Drug Deliv. 2013;287.Google Scholar
  17. 17.
    Jiao J. Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery. Adv Drug Deliv Rev. 2008;60(15):1663–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Seyfoddin A, Shaw J, Al-Kassas R. Solid lipid nanoparticles for ocular drug delivery. Drug Deliv. 2010;17(7):467–89.CrossRefPubMedGoogle Scholar
  19. 19.
    Popov A, Enlow EM, Bourassa J, Gardner CR, Chen H, Ensign LM et al. Inventors; The Johns Hopkins University, assignee. Nanocrystals, compositions, and methods that aid particle transport in mucus. Baltimore, MD. US 9056057. 2013.Google Scholar
  20. 20.
    Tuomela A, Liu P, Puranen J, Rönkkö S, Laaksonen T, Kalesnykas G, et al. Brinzolamide nanocrystal formulations for ophthalmic delivery: reduction of elevated intraocular pressure in vivo. Int J Pharm. 2014;467(1):34–41.CrossRefPubMedGoogle Scholar
  21. 21.
    Reimondez-Troitiño S, Csaba N, Alonso M, de la Fuente M. Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm. 2015;95:279–93.Google Scholar
  22. 22.
    Holly FJ. Formation and stability of the tear film. Int Ophthalmol Clin. 1973;13(1):73–96.CrossRefPubMedGoogle Scholar
  23. 23.
    Gunda S, Hariharan S, Mitra AK. Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits. J Ocul Pharmacol Ther. 2006;22(6):465–76.CrossRefPubMedGoogle Scholar
  24. 24.
    Grass GM, Robinson JR. Mechanisms of corneal drug penetration I: in vivo and in vitro kinetics. J Pharm Sci. 1988;77(1):3–14.CrossRefPubMedGoogle Scholar
  25. 25.
    K-i H, Lee VH, Kim K-J. Roles of the conjunctiva in ocular drug delivery: a review of conjunctival transport mechanisms and their regulation. Eur J Pharm Biopharm. 2005;60(2):227–40.CrossRefGoogle Scholar
  26. 26.
    Kim YC, Oh KH, Edelhauser HF, Prausnitz MR. Formulation to target delivery to the Ciliary body and choroid via the suprachoroidal space of the eye using microneedles. Eur J Pharm Biopharm. 2015;95:398–406.Google Scholar
  27. 27.
    Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: a review. Open ophthalmol J. 2010;4:52–9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006;58(11):1131–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348–60.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov Today. 2008;13(3):144–51.CrossRefPubMedGoogle Scholar
  31. 31.
    Baeyens V, Gurny R. Chemical and physical parameters of tears relevant for the design of ocular drug delivery formulations. Pharm Acta Helv. 1997;72(4):191–202.CrossRefPubMedGoogle Scholar
  32. 32.
    Coursey TG, Henriksson JT, Marcano DC, Shin CS, Isenhart LC, Ahmad F, et al. Dexamethasone nanowafer as an effective therapy for dry eye disease. J Control Release. 2015;213:168–74.CrossRefPubMedGoogle Scholar
  33. 33.
    Bron A, Tiffany J, Gouveia S, Yokoi N, Voon L. Functional aspects of the tear film lipid layer. Exp Eye Res. 2004;78(3):347–60.CrossRefPubMedGoogle Scholar
  34. 34.
    Ranta V-P, Mannermaa E, Lummepuro K, Subrizi A, Laukkanen A, Antopolsky M, et al. Barrier analysis of periocular drug delivery to the posterior segment. J Control Release. 2010;148(1):42–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Ye T, Yuan K, Zhang W, Song S, Chen F, Yang X, et al. Prodrugs incorporated into nanotechnology-based drug delivery systems for possible improvement in bioavailability of ocular drugs delivery. Asian J Pharm Sci. 2013;8(4):207–17.CrossRefGoogle Scholar
  36. 36.
    X-j Y, Wang Y, Fu-Shin XY. Corneal epithelial tight junctions and their response to lipopolysaccharide challenge. Invest Ophthalmol Vis Sci. 2000;41(13):4093–100.Google Scholar
  37. 37.
    Toda R, Kawazu K, Oyabu M, Miyazaki T, Kiuchi Y. Comparison of drug permeabilities across the blood–retinal barrier, blood–aqueous humor barrier, and blood–brain barrier. J Pharm Sci. 2011;100(9):3904–11.CrossRefPubMedGoogle Scholar
  38. 38.
    Raviola G. The structural basis of the blood-ocular barriers. Exp Eye Res. 1977;25:27–63.CrossRefPubMedGoogle Scholar
  39. 39.
    Cunha-Vaz J. The blood-retinal barriers. Doc Ophthalmol. 1976;41(2):287–327.CrossRefPubMedGoogle Scholar
  40. 40.
    Khurana V, Patel SP, Agrahari V, Pal D, Mitra AK. Novel pentablock copolymer based nanoparticles containing pazopanib: a potential therapy for ocular neovascularization. Recent Pat Nanomedicine. 2014;4(1):57–68.CrossRefGoogle Scholar
  41. 41.
    Almazan A, Lee SS, Ross AD, Robinson MR. 7 Barriers to transscleral drug delivery to the retina. Ocular Drug Delivery Systems: Barriers and Application of Nanoparticulate Systems. 2012;133.Google Scholar
  42. 42.
    Gaudana R, Barot M, Patel A, Khurana V, Mitra AK. Barriers for posterior segment ocular drug delivery. In: Mitra AK, editor. Treatise on Ocular Drug Delivery. Bentham E Books, 2013;68–95.Google Scholar
  43. 43.
    Occhiutto ML, Freitas FR, Maranhao RC, Costa VP. Breakdown of the blood-ocular barrier as a strategy for the systemic use of nanosystems. Pharmaceutics. 2012;4(2):252–75.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Pijls RT, Cruysberg LP, Nuijts RM, Dias AA, Koole LH. Capacity and tolerance of a new device for ocular drug delivery. Int J Pharm. 2007;341(1):152–61.CrossRefPubMedGoogle Scholar
  45. 45.
    Fangueiro J, Veiga F, Silva A, Souto E. Ocular drug delivery-new strategies for targeting anterior and posterior segments of the eye. Curr Pharm Des. 2016;22(9):1135–46.Google Scholar
  46. 46.
    Suresh PK, Sah AK. Nanocarriers for ocular delivery for possible benefits in the treatment of anterior uveitis: focus on current paradigms and future directions. Expert Opin Drug Deliv. 2014;11(11):1747–68.CrossRefPubMedGoogle Scholar
  47. 47.
    Sakurai E, Ozeki H, Kunou N, Ogura Y. Effect of particle size of polymeric nanospheres on intravitreal kinetics. Ophthalmic Res. 2001;33(1):31–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Bourges J-L, Gautier SE, Delie F, Bejjani RA, Jeanny J-C, Gurny R, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci. 2003;44(8):3562–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Dilnawaz F, Sahoo SK. Nanotechnology-based ophthalmic drug delivery system. Focal controlled drug delivery. Springer; 2014. p. 225–41.Google Scholar
  50. 50.
    Diebold Y, Jarrín M, Saez V, Carvalho EL, Orea M, Calonge M, et al. Ocular drug delivery by liposome–chitosan nanoparticle complexes (LCS-NP). Biomaterials. 2007;28(8):1553–64.CrossRefPubMedGoogle Scholar
  51. 51.
    Radomska-Soukharev A, Wojciechowska J. Microemulsions as potential ocular drug delivery systems: phase diagrams and physical properties depending on ingredients. Acta Pol Pharm. 2005;62(6):465–71.PubMedGoogle Scholar
  52. 52.
    Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45(1):89–121.CrossRefPubMedGoogle Scholar
  53. 53.
    Jiang J, Moore JS, Edelhauser HF, Prausnitz MR. Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res. 2009;26(2):395–403.CrossRefPubMedGoogle Scholar
  54. 54.
    Bariya SH, Gohel MC, Mehta TA, Sharma OP. Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol. 2012;64(1):11–29.CrossRefPubMedGoogle Scholar
  55. 55.
    Abdelkader H, Wu Z, Al-Kassas R, Alany RG. Niosomes and discomes for ocular delivery of naltrexone hydrochloride: morphological, rheological, spreading properties and photo-protective effects. Int J Pharm. 2012;433(1):142–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Yavuz B, Bozdağ Pehlivan S, Ünlü N. Dendrimeric systems and their applications in ocular drug delivery. Sci World J. 2013;2013:1–13.CrossRefGoogle Scholar
  57. 57.
    Christie JG, Kompella UB. Ophthalmic light sensitive nanocarrier systems. Drug Discov Today. 2008;13(3):124–34.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today. 2003;8(24):1112–20.CrossRefPubMedGoogle Scholar
  59. 59.
    Katzer T, Chaves P, Bernardi A, Pohlmann A, Guterres SS, Ruver Beck RC. Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity. J Microencapsul. 2014;31(6):519–28.CrossRefPubMedGoogle Scholar
  60. 60.
    Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int J Pharm. 2003;255(1):13–32.CrossRefPubMedGoogle Scholar
  61. 61.
    Patravale V, Kulkarni R. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827–40.CrossRefPubMedGoogle Scholar
  62. 62.
    Malkani A, Date AA, Hegde D. Celecoxib nanosuspension: single-step fabrication using a modified nanoprecipitation method and in vivo evaluation. Drug Deliv Transl Res. 2014;4(4):365–76.CrossRefPubMedGoogle Scholar
  63. 63.
    Shelar DB, Pawar SK, Vavia PR. Fabrication of isradipine nanosuspension by anti-solvent microprecipitation–high-pressure homogenization method for enhancing dissolution rate and oral bioavailability. Drug Deliv Transl Res. 2013;3(5):384–91.CrossRefPubMedGoogle Scholar
  64. 64.
    Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015;10(1):13–23.CrossRefGoogle Scholar
  65. 65.
    Chen H, Khemtong C, Yang X, Chang X, Gao J. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today. 2011;16(7):354–60.CrossRefPubMedGoogle Scholar
  66. 66.
    Junghanns J-UA, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295–310.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Möschwitzer JP. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm. 2013;453(1):142–56.CrossRefPubMedGoogle Scholar
  68. 68.
    Sun B, Yeo Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr Opin Solid State Mater Sci. 2012;16(6):295–301.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov. 2004;3(9):785–96.CrossRefPubMedGoogle Scholar
  70. 70.
    Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2006;62(1):3–16.CrossRefPubMedGoogle Scholar
  71. 71.
    Gulsun T, Gursoy R, Levent O. Nanocrystal technology for oral delivery of poorly water soluble drugs. FARAD J Pharm Sci. 2009;34:55–65.Google Scholar
  72. 72.
    Shah T, Patel D, Hirani J, Amin A. Nanosuspensions as a drug delivery system: a comprehensive review. Drug Deliv Technol. 2007;7(9):42–52.Google Scholar
  73. 73.
    Merisko-Liversidge E, Liversidge GG. Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev. 2011;63(6):427–40.CrossRefPubMedGoogle Scholar
  74. 74.
    Sinha B, Müller RH, Möschwitzer JP. Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm. 2013;453(1):126–41.CrossRefPubMedGoogle Scholar
  75. 75.
    de Waard H, Frijlink HW, Hinrichs WL. Bottom-up preparation techniques for nanocrystals of lipophilic drugs. Pharm Res. 2011;28(5):1220–3.CrossRefPubMedGoogle Scholar
  76. 76.
    Chin WWL, Parmentier J, Widzinski M, Tan EH, Gokhale R. A brief literature and patent review of nanosuspensions to a final drug product. J Pharm Sci. 2014;103(10):2980–99.CrossRefPubMedGoogle Scholar
  77. 77.
    Gadad A, Kumar SV, Dandagi P, Bolmol U, Pallavi NP. Nanoparticles and their therapeutic applications in pharmacy. Int J Pharm Sci Nanotechnol. 2014;7(3):2509–19.Google Scholar
  78. 78.
    Che E, Zheng X, Sun C, Chang D, Jiang T, Wang S. Drug nanocrystals: a state of the art formulation strategy for preparing the poorly water-soluble drugs. Asian J Pharm Sci. 2012;7(2):85–95.Google Scholar
  79. 79.
    Keck C. Nanocrystals and amorphous nanoparticles and method for production of the same by a low energy process. US 9040105. 2012.Google Scholar
  80. 80.
    Müller RH, Gohla S, Keck CM. State of the art of nanocrystals–special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Petersen R. inventor Nanocrystals for use in topical cosmetic formulations and method of production thereof patent US 20100047297. 2010.Google Scholar
  82. 82.
    Haynes DH. inventor Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs. US 5091188. 1992.Google Scholar
  83. 83.
    Scholz P, Arntjen A, Müller RH, Keck CM. ARTcrystal® process for industrial nanocrystal production—optimization of the ART MICCRA pre-milling step. Int J Pharm. 2014;465(1):388–95.CrossRefPubMedGoogle Scholar
  84. 84.
    Liversidge GG, Cundy KC, Bishop JF, Czekai DA. inventors; Sterling Drug Inc., assignee. Surface modified drug nanoparticles. New York. US 5145684, 1992.Google Scholar
  85. 85.
    Srivalli KMR, Mishra B. Drug nanocrystals: a way toward scale-up. Saudi Pharm J. 2014:1–19Google Scholar
  86. 86.
    Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanoparticle Res. 2008;10(5):845–62.CrossRefGoogle Scholar
  87. 87.
    Krause K, Müller R. Production and characterisation of highly concentrated nanosuspensions by high pressure homogenisation. Int J Pharm. 2001;214(1):21–4.CrossRefPubMedGoogle Scholar
  88. 88.
    Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1):129–39.CrossRefPubMedGoogle Scholar
  89. 89.
    Baba K, Tanaka Y, Kubota A, Kasai H, Yokokura S, Nakanishi H, et al. A method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye. J Control Release. 2011;153(3):278–87.CrossRefPubMedGoogle Scholar
  90. 90.
    Ali HS, York P, Ali AM, Blagden N. Hydrocortisone nanosuspensions for ophthalmic delivery: a comparative study between microfluidic nanoprecipitation and wet milling. J Control Release. 2011;149(2):175–81.CrossRefPubMedGoogle Scholar
  91. 91.
    Kassem M, Rahman AA, Ghorab M, Ahmed M, Khalil R. Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm. 2007;340(1):126–33.CrossRefPubMedGoogle Scholar
  92. 92.
    Baba K, Nishida K. Steroid nanocrystals prepared using the nano spray dryer B-90. Pharmaceutics. 2013;5(1):107–14.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Gupta S, Samanta MK, Raichur AM. Dual-drug delivery system based on in situ gel-forming nanosuspension of forskolin to enhance antiglaucoma efficacy. AAPS PharmSciTech. 2010;11(1):322–35.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Nagai N, Yoshioka C, Mano Y, Tnabe W, Ito Y, Okamoto N, et al. A nanoparticle formulation of disulfiram prolongs corneal residence time of the drug and reduces intraocular pressure. Exp Eye Res. 2015;132:115–23.CrossRefPubMedGoogle Scholar
  95. 95.
    Nagai N, Ono H, Hashino M, Ito Y, Okamoto N, Shimomura Y. Improved corneal toxicity and permeability of tranilast by the preparation of ophthalmic formulations containing its nanoparticles. J Oleo Sci. 2014;63(2):177–86.CrossRefPubMedGoogle Scholar
  96. 96.
    Kim JH, Jang SW, Han SD, Hwang HD, Choi H-G. Development of a novel ophthalmic ciclosporin A-loaded nanosuspension using top-down media milling methods. Pharmazie. 2011;66(7):491–5.PubMedGoogle Scholar
  97. 97.
    Schopf L, Enlow E, Popov A, Bourassa J, Chen H. Ocular pharmacokinetics of a novel loteprednol etabonate 0.4% ophthalmic formulation. Ophthalmol Ther. 2014;3(1–2):63–72.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Baba K, Nishida K, Hashida N, inventors; Osaka University, assignee. Method for producing an aqueous dispersion of drug nanoparticles and use thereof. Osaka, US 20150087624, 2015.Google Scholar
  99. 99.
    Sharma RK, Yassin AEB. Nanostructure-based platforms-current prospective in ophthalmic drug delivery. Indian J Ophthalmol. 2014;62(7):768–72.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Pawar VK, Singh Y, Meher JG, Gupta S, Chourasia MK. Engineered nanocrystal technology: in-vivo fate, targeting and applications in drug delivery. J Control Release. 2014;183:51–66.CrossRefPubMedGoogle Scholar
  101. 101.
    Müller RH, Shegokar R, Gohla S, Keck CM. Nanocrystals: production, cellular drug delivery, current and future products. Intracellular Delivery. Springer; 2011. pp. 411–32.Google Scholar
  102. 102.
    Xu Q, Kambhampati SP, Kannan RM. Nanotechnology approaches for ocular drug delivery. Middle East Afr J Ophthalmol. 2013;20(1):26–37.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Ravichandran R. Nanoparticles in drug delivery: potential green nanobiomedicine applications. Int J Green Nanotechnol Biomed. 2009;1(2):B108–30.Google Scholar
  104. 104.
    Zimmer A, Kreuter J. Microspheres and nanoparticles used in ocular delivery systems. Adv Drug Deliv Rev. 1995;16(1):61–73.CrossRefGoogle Scholar
  105. 105.
    Wang Y, Zheng Y, Zhang L, Wang Q, Zhang D. Stability of nanosuspensions in drug delivery. J Control Release. 2013;172(3):1126–41.CrossRefPubMedGoogle Scholar
  106. 106.
    Verma S, Kumar S, Gokhale R, Burgess DJ. Physical stability of nanosuspensions: investigation of the role of stabilizers on Ostwald ripening. Int J Pharm. 2011;406(1):145–52.CrossRefPubMedGoogle Scholar
  107. 107.
    Ghosh I, Bose S, Vippagunta R, Harmon F. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int J Pharm. 2011;409(1):260–8.CrossRefPubMedGoogle Scholar
  108. 108.
    Kesisoglou F, Panmai S, Wu Y. Nanosizing—oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59(7):631–44.CrossRefPubMedGoogle Scholar
  109. 109.
    Müller R, Keck C. Twenty years of drug nanocrystals: where are we, and where do we go? Eur J Pharm Biopharm. 2012;80(1):1–3.CrossRefPubMedGoogle Scholar

Copyright information

© Controlled Release Society 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Pharmaceutical Technology, Institute of PharmacyNirma UniversityAhmedabadIndia

Personalised recommendations