Indomethacin-incorporated microemulsion-laden contact lenses for improved ocular drug delivery and therapeutic efficacy

Abstract

Conventional eye drops are associated with several limitations, including rapid drug clearance and low bioavailability, with only about 5% of the administered drug reaching the cornea to demonstrate therapeutic efficacy. Thus, to address these challenges, indomethacin (IND)-loaded microemulsion (Me)-embedded soft contact lenses (CLs) were developed to improve ocular drug delivery. The D-optimal mixture design was employed to optimize the composition of the Me formulation. Independent variables included Capmul MCM (oil phase), S _mix (Tween 80/isopropyl alcohol), and water, while dependent variables were the globule size, transmittance (%), and drug release profile. The optimized Me exhibited a globule diameter of 45.69 ± 1.85 nm and a transmittance of 99.4% ± 1.59%. The globule dispersion index (PDI) was 0.33 ± 0.06, and the zeta potential (ZP) was 0.657 ± 0.012 mV. Soft CLs were developed using free radical polymerization and fortified with the Me loaded with the drug through direct loading and soaking techniques. Direct loading achieved a swelling percentage of 96.37% ± 1.8% and a transmittance of 96.5% ± 0.3%, while soaking resulted in 97.57% ± 1.4% swelling and 97.3% ± 1.3% transmittance. A drug content of 19.76 ± 0.23 μg per lenses for direct loading and 29.8 ± 0.2 μg per lenses for soaking demonstrated that the efficacy of the soaking technique was higher than that of direct loading. Moreover, drug release studies showed that the Me-laden lenses prepared using the direct loading technique released 44.00% ± 0.53% to 53.00% ± 0.59% of the drug within the first 6 h, while the lenses prepared via soaking released 62.58% ± 1.56% to 97.64% ± 1.52% of the drug within the first 6 h, followed by regulated drug release for up to 28 h, maintaining clarity and drug loading. Ocular irritancy test results indicated negligible irritation, suggesting that the Me-laden lenses are a safe and effective platform to manage ocular inflammation with the controlled delivery of IND.

Fig. 1. Solubility study of indomethacin in oil (a), surfactants (b) and co-surfactants (c).

Fig. 2. Pseudo ternary phase diagram for the (1 : 1) S_mix ratio (a) and (2 : 1) S_mix ratio (b).

Fig. 3. Pseudo-ternary phase diagram for the (1 : 2) S_mix ratio (a) and (4 : 1) S_mix ratio (b).

Fig. 4. Contour plot for the response (Y1) (a), 3D plots of the response (Y1) (b), and contour plot for the response (Y2) (c).

Fig. 5. 3D contour plot for the response (Y2) (a), 3D plots of the response (Y3) (b), and contour plot for the response (Y3) (c).

Fig. 6. Overlay plot of the optimized batch.

Fig. 7. Representative H&E staining images of the cornea (negative control, NaCl, 0.9%) (a); positive control, ethanol (b); and test formulation, indomethacin (c). EP: Epithelium; BM: Bowman Layer; STR: Stroma.