PMID- 28232270
OWN - NLM
STAT- MEDLINE
DCOM- 20170816
LR  - 20170816
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 522
IP  - 1-2
DP  - 2017 Apr 30
TI  - Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived 
      from the PK-Eye.
PG  - 119-127
LID - S0378-5173(17)30137-0 [pii]
LID - 10.1016/j.ijpharm.2017.02.047 [doi]
AB  - Corticosteroids have long been used to treat intraocular inflammation by 
      intravitreal injection. We describe dexamethasone loaded 
      poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by 
      thermally induced phase separation (TIPS). The dexamethasone loaded 
      microparticles were evaluated using a two-compartment, in vitro aqueous outflow 
      model of the eye (PK-Eye) that estimates drug clearance time from the back of the 
      eye via aqueous outflow by the anterior route. A dexamethasone dose of 
      0.20+/-0.02mg in a 50muL volume of TIPS microparticles resulted in a clearance 
      t(1/2) of 9.6+/-0.3days using simulated vitreous in the PK-Eye. Since 
      corticosteroids can also clear through the retina, it is necessary to account for 
      clearance through the back of the eye. Retinal permeability data, published human 
      ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to 
      establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times 
      of corticosteroid formulations. A t(1/2) of 48h was estimated for the 
      dexamethasone-TIPS microparticles, which is almost 9 times longer than that 
      reported for dexamethasone suspension in humans. The prediction of human 
      clearance times of permeable molecules from the vitreous compartment can be 
      determined by accounting for drug retinal permeation and determining the 
      experimental clearance via the anterior aqueous outflow pathway using the PK-Eye.
CI  - Copyright (c) 2017. Published by Elsevier B.V.
FAU - Awwad, Sahar
AU  - Awwad S
AD  - National Institute for Health Research (NIHR) Biomedical Research Centre at 
      Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, 
      London, EC1 V9EL, UK; UCL School of Pharmacy, London, WC1N 1AX, UK.
FAU - Day, Richard M
AU  - Day RM
AD  - UCL Division of Medicine, London, WC1E 6JJ, UK.
FAU - Khaw, Peng T
AU  - Khaw PT
AD  - National Institute for Health Research (NIHR) Biomedical Research Centre at 
      Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, 
      London, EC1 V9EL, UK.
FAU - Brocchini, Steve
AU  - Brocchini S
AD  - National Institute for Health Research (NIHR) Biomedical Research Centre at 
      Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, 
      London, EC1 V9EL, UK; UCL School of Pharmacy, London, WC1N 1AX, UK. Electronic 
      address: ucnvsbr@ucl.ac.uk.
FAU - Fadda, Hala M
AU  - Fadda HM
AD  - Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, 
      Butler University, Indianapolis, IN 46208, USA. Electronic address: 
      hfadda@butler.edu.
LA  - eng
PT  - Journal Article
DEP - 20170221
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Administration, Ophthalmic
MH  - Algorithms
MH  - Anti-Inflammatory Agents/*administration & dosage/*chemistry/pharmacokinetics
MH  - Delayed-Action Preparations
MH  - Dexamethasone/*administration & dosage/*chemistry/pharmacokinetics
MH  - Eye/*metabolism
MH  - Half-Life
MH  - Humans
MH  - Intravitreal Injections
MH  - Models, Anatomic
MH  - Nanoparticles
MH  - Permeability
MH  - Retina/metabolism
MH  - Vitreous Body/metabolism
OTO - NOTNLM
OT  - In vitro in vivo correlations
OT  - Ocular drug delivery
OT  - PLGA
OT  - Pharmacokinetics
OT  - Sustained release
EDAT- 2017/02/25 06:00
MHDA- 2017/08/17 06:00
CRDT- 2017/02/25 06:00
PHST- 2016/12/02 00:00 [received]
PHST- 2017/02/02 00:00 [revised]
PHST- 2017/02/17 00:00 [accepted]
PHST- 2017/02/25 06:00 [pubmed]
PHST- 2017/08/17 06:00 [medline]
PHST- 2017/02/25 06:00 [entrez]
AID - S0378-5173(17)30137-0 [pii]
AID - 10.1016/j.ijpharm.2017.02.047 [doi]
PST - ppublish
SO  - Int J Pharm. 2017 Apr 30;522(1-2):119-127. doi: 10.1016/j.ijpharm.2017.02.047. 
      Epub 2017 Feb 21.