Drug delivery to the posterior segment of the eye IV: theoretical formulation of a drug delivery system for subconjunctival injection.
OBJECTIVE
The aim of the current study was to provide insights on the proper design of a dosage form to deliver drugs to the back of the eye, as well as to estimate the likelihood of achieving therapeutic levels by subconjunctival injection.


METHODS
Computer simulation of a validated pharmacokinetic model for a subconjunctival injection was performed. The effect of various rate constants, different methods of administration, and other factors, such as solubility, etc., on the vitreous drug levels, were investigated.


RESULTS
It was discovered, as expected, that a simple injection is not practical for chronic diseases, since frequent injection is required. A zero-order release system is able to provide a steady vitreous drug level. However, it may not provide vitreous drug levels greater than 1 microg/mL, unless k(10) can be reduced by a factor of 100 via the formulation modifications. A first-order release system gives a vitreous level between that following a simple subconjunctival injection and the injection of a zero-order release system.


CONCLUSIONS
A properly designed delivery system, which can solubilize poorly soluble compounds and sustain vitreous drug levels for an extended period of time, is required for effective drug delivery to the back of the eye by subconjunctival injection.
Lee
Thomas Wai-Yip
TW
Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. thlee@celgene.com
Robinson
Joseph R
JR
D000818:Animals; D003198:Computer Simulation; D003228:Conjunctiva / Q000378:metabolism*; D004304:Dosage Forms; D004333:Drug Administration Routes; D004339:Drug Compounding; D016503:Drug Delivery Systems; D007267:Injections; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D012995:Solubility; D014822:Vitreous Body / Q000378:metabolism*
D004304:Dosage Forms; D004364:Pharmaceutical Preparations