, , , ,

By: Haley Porter

photo_haley-porterNepafenac is a common NSAID used to treat pain and inflammation in the cornea following Lasik or cataracts surgery. Nepafenac is very lipophilic; therefore, it is currently only available as a commercial suspension.

Suspensions are undesirable for three reasons.  First, suspensions can cause ocular irritation. The feeling of dropping a suspension in your eye is similar to the discomfort of sand in your eye at the beach. This irritation is immediately followed by lacrimation, which leads to the second problem: increasing tear rate. Increasing tear rate leads to a decrease in residence time, which is the amount of time the drug has to reach the cornea. When residence time is decreased, repeat administration is required. However, due to the irritation caused by the commercial product, patient compliance is low.

The third problem is that the drug is too lipophilic to make it to the cornea, due to the makeup of the three tear film layers. The outermost layer of tear film is the lipid layer, and thus the drug has no problem distributing into this layer; however, to make it to the cornea, the drug must pass through two aqueous-based layers: aqueous layer (middle layer) and mucin layer (closest to the cornea). Before the drug can pass through the two aqueous layers, the drug is washed away due to lacrimation, resulting from the particle irritation. For this reason, the commercial formulation is highly concentrated since very little actually makes it to the eye. This is wasteful use of the drug and not cost effective.graphic_tear-film-comparison

My research focuses on developing a solution formulation that decreases irritation by solubilization of the drug, as well as enhancing residence time to improve patient compliance. Cyclodextrin is a cone shaped molecule with a hydrophobic core and hydrophilic shell. Interacting cyclodextrin with nepafenac gives the nepafenac a hydrophilic shell, allowing the drug to dissolve into a solution, which can pass through all of the tear film layers without causing irritation to the patient.

The second key component of this formulation is an in-situ gel former, meaning it is a solution in a normal environment and then forms a gel once it interacts with the ions of the tear film. When dropped on the eye, this formulation produces a gel matrix that increases residence time of the drug, allowing for a slow diffusion of drug-cyclodextrin complexes through all of the layers of the tear film to the cornea where the drug is safely released from the cyclodextrin. This aspect of the formulation could decrease the number of times a patient needs to administer the product.

In summary, this in-situ solution formulation would be more patient friendly compared to the commercial product because it has the potential to be more cost effective and comfortable with fewer daily doses needed, due to its sustained release formulation. Overall, this formulation could be the solution to the problems patients experience when using the commercial brand.

Haley Porter has a Bachelor’s in Chemical Engineering and is currently pursuing her Ph.D. in Pharmaceutics at Auburn University. Her research focuses on improving formulations of lipophilic drugs, currently available on the market. Her poster was 7th most viewed at the 2016 Annual AAPS Meeting.