Corneal Critical Barrier against the Penetration of Dexamethasone and Lomefloxacin Hydrochloride: Evaluation by the Activation Energy for Drug Partition and Diffusion in Cornea

Abstract

The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approach to investigate the mechanism of drug permeability.

Asymmetry in Drug Permeability through the Cornea

“…The lag time t lag needed to reach a steady state flux across the cornea is related to tissue thickness, H, by Equation (4) [ 47 ] and is, therefore, mainly controlled by the stroma [ 48 ] with H = 600 µm [ 46 ]. Then, the lag time t lag ≈ 2.3 h ( Table 1 ) leads to the diffusivity of bromfenac sodium through the stroma D = 7 × 10 −12 m 2 /s.…”

“…Then, the lag time t lag ≈ 2.3 h ( Table 1 ) leads to the diffusivity of bromfenac sodium through the stroma D = 7 × 10 −12 m 2 /s. The permeability coefficient of the stroma can be obtained from Equation (5) [ 47 ]: t lag = H 2 / (6 D) P coeff = D K/H …”

Moxifloxacin modifies corneal fibroblast‐to‐myofibroblast differentiation

“…Because higher tissue level could be achieved by adding retention‐enhancing agent in the formula (Lindstrom et al ., ), careful dosage adjustment could thus provide reasonable antimicrobial and anti‐fibrotic effects. Furthermore, as corneal epithelium is a critical barrier to topically applied medication (Yasueda et al ., ), corneal penetration of topically applied antibiotics would increase tremendously in cases with corneal epithelial defects, such as corneal ulcers. We suggest that stromal concentration of higher than 100 μg·mL –1 could be achieved by topical frequent application of 5 mg·mL –1 MOX in these cases.…”

Routes for drug deliverytopical, transscleral, suprachoroidal, and intravitreal gas-phase nanoparticles

“…33 Some of the epithelial barrier is broken down partially by the preservative benzalkonium chloride, thereby providing increased penetration of various compounds through the epithelium. 33 Some of the epithelial barrier is broken down partially by the preservative benzalkonium chloride, thereby providing increased penetration of various compounds through the epithelium.…”