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Ultrastructural changes to the corneal endothelium due to benzalkonium chloride.

Ten normal and 20 keratectomised corneas received hourly drops of vehicle with or without benzalkonium chloride (0.02% BAC or 0.01% BAC plus 0.1% disodium ethylenediaminetetraacetate) over the daylight hours of 2 days (18 applications). When applied to the intact cornea, BAC with or without Na2EDTA caused only slight clarification of the endothelial cytoplasm, whilst in a few mitochondria the cristae were displaced. In the keratectomised corneas receiving BAC, the majority of mitochondria of the central endothelial cells were pale and swollen or even disrupted. Many contained aggregations of membranous material either within the mitochondrion or at its outer membrane. The peripheral endothelium was much less affected than the central area of endothelium behind the keratectomy. These results suggest that BAC should not be administered to corneas in which the anterior epithelial barrier is incomplete.

Animals↗

In vitro studies on the use of cetylpyridinium chloride as a bacterial plaque control agent.

Studies have shown that cetylpyridinium chloride (CPC) containing mouthwash may in vitro inhibit artificial bacterial plaque accumulation under certain conditions. These studies, together with the findings of clinical trials, suggest that the clinical activity of CPC in partially limiting plaque accumulation depends on its adherence to cleaned enamel surfaces rather than its penetration in performed plaque.

Adsorption↗

The interaction of preservatives with polyhydroxyethylmethacrylate (polyHEMA).

The interaction of the four most commonly used preservatives in contact lens solutions (chlorbutol, thiomersal, chlorhexidine gluconate and benzalkonium chloride) with polyhydroxyethylmethacrylate (polyHEMA), has been examined. Benzalkonium chloride and chlorhexidine gluconate show typical high affinity type isotherms. The interaction of benzalkonium chloride with polyHEMA from aqueous solution was reversible whereas that of chlorhexidine was only reversible in the presence of electrolyte or surfactant. Chlorbutol showed a typical reversible linear isotherm. Thiomersal does not interact with polyHEMA above pH 5.0. The extent of chlorhexidine--polyHEMA interactions in increased by the presence of formulatory adjuvants such as electrolyte and hydrophilic polymers. PolyHEMA lenses that apparently have been equilibrated with chlorhexidine gluconate will, on the addition of fresh preservative solution, bind further quantities of chlorhexidine above that which would be predicted from the sorption isotherm.

Acrylic Resins↗

Altered ocular absorption and disposition of sodium cromoglycate upon ion-pair and complex coacervate formation with dodecylbenzyldimethylammonium chloride.

Ion-pair formation between the dianionic drug sodium cromoglycate and dodecylbenzyldimethylammonium chloride has been found to alter the extent and rate of corneal penetration of both large ions upon their coadministration. Additionally, using a complex coacervate of the two large ions as the applied dose form (in which the complex is in equilibrium with the ion pairs), a change in the overall disposition of both large ions to the various components of the eye is observed.

Absorption↗

The use of a radiolabelled saccharin solution to monitor the effect of the preservatives thiomersal, benzalkonium chloride and EDTA on human nasal clearance.

The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.

Adult↗

Effect of preservatives on systemic delivery of insulin by ocular instillation in rabbits.

The effects of absorption promoters and ophthalmic preservatives on the systemic absorption of insulin through the ocular route were investigated in albino rabbits. Insulin absorption was evaluated by its hypoglycaemic response. Although ocular instillation of insulin alone did not decrease the serum glucose concentration, instillation of insulin with absorption promoters such as EDTA and saponin decreased it. The promoting effect depended on the concentration of the absorption promoters. Of ophthalmic preservatives investigated (benzalkonium chloride, paraben, 2-phenylethanol, benzyl alcohol and sorbic acid), benzalkonium, chloride and paraben showed promoting effects. The promoting effect for benzalkonium chloride was reversible and dependent on concentration of both benzalkonium chloride and insulin in the formulation.

Absorption↗