Abstract
Purpose: :
To investigate the effect of formulation parameters on interfacial interactions of topically instilled tear substitutes with the rabbit ocular surface.
Methods: :
The studied formulations were Saline 0.9%; HyloComod® (Ursapharm); HypoTears®, GenTeal® (Novartis); Refresh®, Celluvisc®, Refresh EnduraTM anionic emulsion (Allergan); and Cationorm® cationic emulsion (Novagali Pharma). Ex–vivo investigated surfaces were cornea and conjunctiva at wet, dry and dry after mucin removal conditions of 21 female albino rabbit eyeglobes. Contact angles were measured by FTA–125/188 systems (First Ten Angstroms Inc.), surface tension was determined by multiwell plate tensiometer (Kibron Inc.) and spreading coefficients were calculated from measured surface tensions and contact angles. Contact angles were auto–determined from single captured frame for FTA–125 system (static method), showing the instilled droplet at its touchdown on the studied surface, and from AVI movie for FTA–188 system (dynamic method), showing hydrodynamic events starting from just before droplet touchdown up to the chosen time limit.
Results: :
Contact angles were significantly lower on wet compared to dry surfaces, but differences between formulations were statistically significant only in the dynamic setting. Contact angles were increased after mucin removal by 11.8–33.7% and 17.7–36.8% for cornea and conjunctiva respectively. The cationic emulsion achieved the lowest contact angles and the highest spreading coefficients on cornea and conjunctiva with or without mucin removal. Contact angles comparison between static and dynamic methods measurements for same formulations revealed 100% and 50% matching for dry and wet surfaces respectively. The cationic emulsion achieved an extremely low contact angle value from the very beginning, while a significant contact angle value was recorded for some formulations up to 30 seconds.
Conclusions: :
Hydration level had the highest impact on the wettability of studied surfaces, while the effect of mucin removal was mild to moderate. The cationic emulsion showed superiority at all studied surfaces, implying a significant role of oil droplet positive surface charge, low surface tension and emulsion ingredients. Our results indicate higher sensitivity of the dynamic method on wet surfaces. The hydrodynamic live data provide a unique insight on eyedrops interaction with ocular surface, a fundamental event in topical ocular therapy.
Keywords: pharmacology • cornea: tears/tear film/dry eye • cornea: surface mucins