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Cationic polystyrene latex was flocculated with mixtures of hydroxypropyl guar (HPG) and boric acid, which form an anionic polyelectrolyte HPG-borate. Flocculation could be reversed by either lowering pH or by adding fructoseboth procedures remove labile borate ions weakly bound to the HPG chains. Mixtures of phenyl boronic acid (PBA) and HPG also flocculate latex although the range of HPG-PBA concentrations, giving flocculation was much narrower than HPG-borate. The differences were explained by the tendency of borate ion to cross-link HPG chains, whereas PBA is monofunctional and cannot cross-link HPG.

The interactions of hydroxypropyl guar (HPG) with boric acid, lysozyme, and mucin were characterized by rheology, light scattering, electrophoresis, and isothermal titration calorimetry to help understand how HPG interacts with tear film components. Borate binds to guar under pH, temperature, and ionic strength conditions representative of those found in the eye. The HPG-borate complexes behave as anionic polyelectrolytes and thus interact with cationic lysozyme, a major tear film protein, whereas HPG-borate does not appear to bind to mucin, an anionic glycoprotein. The interactions of HPG, borate, lysozyme, and mucin can be explained by two physical interactions: (1) pH-dependent binding of borate to carbohydrates and (2) the electrostatic attraction of oppositely charged macromolecules.

Purpose: The purpose of these investigations was to develop an improved method for measuring precorneal residence time (RT) and to demonstrate its efficacy with novel formulations., Methods: A biomicroscope was adapted for use as a clinical fluorometer. Using a nonpenetrating fluorescent probe (FITC-dextran, 70,000-73,000 molecular weight [MW]), RT was estimated as the time to return to baseline (gross RT) and from parameters derived from least-squares regression fits to the decay data (area under the curve [AUC], elimination rate, and time for 50% of the signal to be eliminated [T(50)]). One rabbit and two human studies were conducted. The studies were randomized, double-masked, and controlled. Repeatability in humans was examined in 15 subjects (six determinations per subject, n = 90 total)., Results: The FITC-dextran tracer did not penetrate into corneal tissue. The rabbit gross RTs were 14.5, 15.0, and 16.0 minutes for three low-viscosity solutions (eta = 2.7-7.7 mPa/sec) and 22.5 minutes for a more viscous solution (eta = 357 mPa/sec). For a high-viscosity (eta approximately equal 30,000 mPa/sec) gel in humans, the method demonstrated approximately a twofold increase in gross RT and AUC compared with buffered saline. Repeatability of the method appeared acceptable, with intersubject variability the most significant factor affecting precision., Conclusions: The new method is safe and convenient and offers comprehensive RT data. Furthermore, it appears to differentiate among formulations. However, as with other tear-influenced parameters, there is significant variability. Thus, sufficient sample sizes are necessary for meaningful comparative investigations.