In Vitro Permeation of Latanoprost Eye Drop Formulations in a 3-Dimensional Normal Human Corneal Tissue Model
Permeation of topically applied ocular drugs occurs predominantly through the cornea and therefore absorption studies using corneal tissues play a critical role in ocular drug formulation. The purpose of the study was to evaluate the permeation of Latanoprost eye drops through in vitro reconstructed normal human corneal tissue model.
Seven different formulations of Latanoprost eye drops were tested for ocular permeation using a reconstructed corneal tissue model (EpiCornealTM). Volumes of 50 or 100 μL of eye drop formulations were applied topically onto the EpiCorneal tissue surface and incubated at standard cell culture conditions (SCC, 37⁰C, 5% CO2). At permeation times of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0 and 12.0 hrs, the tissues were moved into new wells filled with receptor medium (Krebs Ringer Buffer, pH 7.4) and returned into SCC. The samples were collected and analyzed with a fully-validated HPLC method for Latanoprost acid determination. Tissue integrity (Lucifer Yellow leakage assay) and tissue viability (MTT assay) were determined after the permeation study.
For each formulation, plots of the % cumulative amount of Latanoprost acid that permeated through the tissue versus time were constructed. From the steady state flux region of the plot (<4 hrs for most formulations), the Papp was calculated. Xalatan eye drops (containing 0.02% BAC solution) had the fastest permeation rate (Papp=8.81cm×s-1) while Monoprost (preservative-free) had the lowest permeation rate (Papp=1.15 cm×s-1). Formulations containing Poloxamer 407 had higher Papp (6.05 and 6.27) when compared to formulations without surfactants (1.69 to 2.57). Tissue integrity and viability were maintained in all experiments as evidenced by Lucifer Yellow and MTT results.
The EpiCorneal tissue demonstrated very high reproducibility and presented a permeation profile of different formulations similar to in vivo.
EpiCorneal, COR-100, Latanoprost, Drug permeation, Lucifer yellow leakage, ophthalmic drug delivery
Latanoprost eye drops, Monoprost, Poloxamer 407, Cremophor RH40, benzalkonium chloride, Xalatan
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