Abstract
Hyperviscosity agents are commonly used in ophthalmic formulations for improving corneal drug penetration by increasing tissue contact time. One such viscosity agent is hydroxypropyl methylcellulose (HPMC). HPMC has been used in riboflavin solutions for photochemical UVA cross-linking (CXL). Sodium hydroxymethylglycinate (SMG) is a small molecule formaldehyde releaser that can function as a therapeutic tissue cross-linker for corneal and scleral applications. The present study was undertaken in order to study formulation factors using HPMC and SMG that could positively influence the cross-linking effect in these ocular tissues. Formulations containing 10 mM SMG and 100 mM sodium bicarbonate were prepared with varying HPMC concentrations from 0 to 4.4%. Their cross-linking effects on porcine and rabbit eyes were measured using differential scanning calorimetry (DSC), expressed as the change/difference in melting temperature (ΔTm) compared with the control. SMG in 4.4% HPMC solution resulted in ΔTm of 6.3 ± 1.21, while other concentration showed no differences in Tm shift on porcine cornea. In ex vivo rabbit cornea, there was a trend toward an increasing cross-linking effect with higher viscosity albeit mild differences. While a significant Tm shift was observed in porcine and rabbit sclera, there was no difference in effect of cross-linking between four HPMC concentrations. Increasing the HPMC concentration does not negatively affect the cross-linking efficacy attributed by SMG and could still be a positive cross-linking enhancer by virtue of increasing tissue contact time in a dynamic biological system. This information will be useful for planning further animal and human studies.
Highlights
Keratoconus is being managed successfully with ultraviolet-A – riboflavin photochemical corneal cross-linking throughout the world, which has revolutionized the field of corneal ectasia and related disorders
Various viscosity agents have been utilized in topical ophthalmic solutions, and 1.1% hydroxypropyl methylcellulose (HPMC) is a concentration often used in commercially available ophthalmic solutions
Increasing the contact time of the drug in the solution can be achieved by increasing the viscosity of the solution; we were still uncertain whether increasing the concentration of HPMC could affect Sodium hydroxymethylglycinate (SMG) efficacy
Summary
Keratoconus is being managed successfully with ultraviolet-A – riboflavin photochemical corneal cross-linking (known as ‘CXL’) throughout the world, which has revolutionized the field of corneal ectasia and related disorders. There are several reasons, to consider the development of topical cross-linking solutions to augment or replace the Dresden procedure, since the procedure does produce post-procedural corneal haze [3], keratocyte apoptosis [4] and changes in corneal microstructure [5,6]. This evidence, in addition to the pain and possible post-operative infection associated with de-epithelialization related to riboflavin’s inability to reliably penetrate the corneal epithelium, points toward the need for a less invasive treatment [7,8].
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