Barriers to Glaucoma Drug Delivery

Abstract

Topical medications remain the mainstay of glaucoma treatment. This review will aim to cover the pharmacokinetics of topically applied drops, the ocular barriers to drug delivery, and the role of ophthalmic drug formulation in enhancing drug delivery to the target tissue while minimizing side effects and increasing patient compliance. Recent advances in surgical techniques, therapeutic approaches, and material sciences have produced exciting new therapies for ocular diseases. The development of new vehicles and drug formulations that require less patient compliance is also discussed, as are the routes of drug delivery for neuroprotection.

Drops, Drops, and More Drops

“…Drug penetration across the corneal epithelial barrier is facilitated by lipophilic, rather than hydrophilic molecular properties. (Ghate and Edelhauser, 2008) These considerations were essential for the development of both the topical carbonic anhydrase inhibitors and the PGAs. Due to the severe ocular irritation associated with the naturally occurring prostaglandins, changes were made to the molecule itself to reduce hyperemic effects, and led to the development of latanoprost.…”

“…However, in studies comparing the different available preservatives, only benzalkonium chloride/EDTA met the European Pharmacopoeia criteria for preservative efficacy. (Ghate and Edelhauser, 2008) Another strategy to lessen side effects is to lower the concentration of the active ingredient. This was recently done successfully with bimatoprost with the introduction of a formulation with a .01% concentration rather than the original .03% concentration of active ingredient.…”

“…However, drugs in suspension have the disadvantage of needing to be resuspended before use by shaking, which reduces the medication adherence rate. (Ghate and Edelhauser, 2008) Patient dexterity Patient vision Ability of patient to lift arm above eye Whether a mirror is used as an aid Whether drops are dispensed into or onto the eye Whether only one drop is dispensed Whether the bottle tip touches the eye Shape and dimensions of the bottle tip Viscosity and surface tension of the drops solution Table 3. Parameters that Affect Drops Instillation Several different formulations have been developed that increase the viscosity of ocular medications, thereby enhancing absorption by increasing the residence time in the conjunctival sac.…”

“…Due to the severe ocular irritation associated with the naturally occurring prostaglandins, changes were made to the molecule itself to reduce hyperemic effects, and led to the development of latanoprost. (Ghate and Edelhauser, 2008) Other topical medications that have solubility problems, such as betaxolol and brinzolamide, can be delivered to the eye as suspensions. However, drugs in suspension have the disadvantage of needing to be resuspended before use by shaking, which reduces the medication adherence rate.…”

Novel drug delivery systems for glaucoma

“…The barriers to transport with drops include the increase in tear drainage with administration of an eye drop, low corneal transport, and low conjunctival and scleral transport. 44 Transport through the ocular tissues is dependent on the particular chemistry of the drug. Hydrophobic molecules have a tendency to accumulate more in the vitreous, whereas hydrophilic molecules tend to show greater concentrations in the aqueous humor.…”