title: Simulating dissolution of intravitreal triamcinolone acetonide suspensions in an anatomically accurate rabbit eye model.
abstract: OBJECTIVE
  A computational fluid dynamics (CFD) study examined the impact of particle size on dissolution rate and residence of intravitreal suspension depots of Triamcinolone Acetonide (TAC).
  
  
  METHODS
  A model for the rabbit eye was constructed using insights from high-resolution NMR imaging studies (Sawada 2002). The current model was compared to other published simulations in its ability to predict clearance of various intravitreally injected materials. Suspension depots were constructed explicitly rendering individual particles in various configurations: 4 or 16 mg drug confined to a 100 microL spherical depot, or 4 mg exploded to fill the entire vitreous. Particle size was reduced systematically in each configuration. The convective diffusion/dissolution process was simulated using a multiphase model.
  
  
  RESULTS
  Release rate became independent of particle diameter below a certain value. The size-independent limits occurred for particle diameters ranging from 77 to 428 microM depending upon the depot configuration. Residence time predicted for the spherical depots in the size-independent limit was comparable to that observed in vivo.
  
  
  CONCLUSIONS
  Since the size-independent limit was several-fold greater than the particle size of commercially available pharmaceutical TAC suspensions, differences in particle size amongst such products are predicted to be immaterial to their duration or performance.
authors.affiliation: Drug Delivery, Alcon Research Ltd., Mail Stop R2-45, 6201 South Freeway, Fort Worth, Texas 76134, USA. paul.missel@alconlabs.com
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Missel
authors.forename: Marc
authors.initials: M
authors.lastname: Horner
authors.forename: R
authors.initials: R
authors.lastname: Muralikrishnan
mesh_terms: D000818:Animals; D003198:Computer Simulation; D008953:Models, Anatomic; D010316:Particle Size; D011817:Rabbits; D012995:Solubility; D013535:Suspensions / Q000737:chemistry; D014222:Triamcinolone Acetonide / Q000737:chemistry*
chemical_list: D013535:Suspensions; D014222:Triamcinolone Acetonide
references.citation: Ann Biomed Eng. 1997 Mar-Apr;25(2):303-14
references.pmid: 9084836
references.citation: Pharm Res. 2002 Nov;19(11):1636-47
references.pmid: 12458669
references.citation: Ann Biomed Eng. 2002;30(9):1128-39
references.pmid: 12502224
references.citation: Exp Eye Res. 1964 Jun;3:156-65
references.pmid: 14211918
references.citation: J Biomech Eng. 2001 Dec;123(6):540-7
references.pmid: 11783724
references.citation: Am J Ophthalmol. 1959 Jan;47(1 Pt 2):361-8
references.pmid: 13617364
references.citation: Curr Eye Res. 1996 Jan;15(1):87-93
references.pmid: 8631208
references.citation: Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3967-71
references.pmid: 12939316
references.citation: Invest Ophthalmol Vis Sci. 2002 Mar;43(3):700-8
references.pmid: 11867587
references.citation: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3553-61
references.pmid: 16186333
references.citation: J Pharm Sci. 1963 Jan;52:67-71
references.pmid: 13954443
references.citation: Exp Eye Res. 1972 Nov;14(3):233-41
references.pmid: 4640871
references.citation: J Control Release. 2000 Mar 1;65(1-2):43-7
references.pmid: 10699268
references.citation: Exp Eye Res. 1991 Jan;52(1):27-39
references.pmid: 1714398
references.citation: Acta Ophthalmol Scand. 2007 May;85(3):339-40
references.pmid: 17362364
references.citation: Retina. 2006 May-Jun;26(5):523-30
references.pmid: 16770258
references.citation: J Pharm Sci. 1998 Dec;87(12):1479-88
references.pmid: 10189253
references.citation: Exp Eye Res. 1984 Dec;39(6):791-805
references.pmid: 6083877
references.citation: Am J Physiol. 1999 Oct;277(4):R1218-29
references.pmid: 10516265
references.citation: Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2135-8
references.pmid: 20019364
references.citation: Ophthalmology. 2003 Apr;110(4):681-6
references.pmid: 12689886
references.citation: Exp Eye Res. 1970 Oct;10(2):243-9
references.pmid: 5484767
references.citation: Invest Ophthalmol Vis Sci. 1995 Aug;36(9):1893-903
references.pmid: 7543465
references.citation: Pharm Res. 2000 Jun;17(6):664-9
references.pmid: 10955838
references.citation: Curr Eye Res. 2002 Sep;25(3):173-7
references.pmid: 12607187
references.citation: J Control Release. 2005 Jul 20;105(3):279-95
references.pmid: 15896868
references.citation: J Pharm Sci. 1997 Jun;86(6):726-32
references.pmid: 9188056
references.citation: J Ocul Pharmacol Ther. 2010 Apr;26(2):137-46
references.pmid: 20415622
references.citation: J Glaucoma. 2001 Feb;10(1):18-24
references.pmid: 11219634
references.citation: J Glaucoma. 1995 Oct;4(5):327-33
references.pmid: 19920695
references.citation: Invest Ophthalmol Vis Sci. 2009 May;50(5):2301-7
references.pmid: 19182250
references.citation: J Pharm Sci. 1983 Feb;72(2):190-3
references.pmid: 6834260
references.citation: Am J Physiol. 1987 Jan;252(1 Pt 2):F104-8
references.pmid: 3812693
references.citation: Invest Ophthalmol Vis Sci. 1993 Jun;34(7):2151-8
references.pmid: 8505198
references.citation: Graefes Arch Clin Exp Ophthalmol. 1986;224(2):113-7
references.pmid: 3949183