Differential tissue-on-tissue lubrication by ophthalmic formulations.

Tissue-on-tissue friction testing was used to determine how instillation of hydrophilic polymer-containing formulations between the "blinking" tissues would compare with lubrication by saline, alone, or an oil-emulsion preparation. Best results were obtained for a formulation that contained active demulcents polyethylene glycol (PEG 400) and propylene glycol (PG), as well as a gellable polymer hydroxypropyl guar (HP-Guar) in a borate-buffered solution, in comparison with hydroxypropylcellulose-containing and carboxymethylcellulose-containing formulations. Superior performance of all the formulations was found for lubricating tissue-on-tissue couples, compared with metal-oxide-to-metal oxide interfaces, or metal oxide-to-tissue interfaces. A reciprocating pin-on-disc type friction/wear test device articulated the intimal faces of preserved human umbilical cord vein segments under increasing loads during simulated continuous "eye-blinking" with addition of increasing weights up to 60 g/cm2, simulating maximal eyelid force on the orbital globe. The tissue-on-tissue couples moved from liquid phase lubrication to boundary lubrication. After residual formulations were rinsed away with saline, persistence of low friction at the highest loads was indicative of formulation substantivity. Human umbilical cord vein segments were utilized in saline-wetted tissue-on-tissue couples that showed variable starting coefficients of friction in the range 0.2-0.4, producing moderate tearing and disruption of the interfacial layers above the medial collagen zone. The best-performing formulations instilled to the tissues pre-wetted with saline apparently reacted separately with each tissue face to produce a lower final and persistent coefficient of friction of about 0.05. Scanning electron microscopy and light microscopy of these guar-modified tissue specimens showed only a few superficial tissue disruptions, and some interphase swelling consistent with polymer uptake. The frictional values for lubricated couples having non-tissue members were considerably higher than the coefficients of friction measured for the similarly lubricated tissue-on-tissue couples, emphasizing the requirement that appropriate simulations are critical to obtaining clinically predictive data.