Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery

Surface tension, conductivity and dye solubilization experiments show that, in aqueous solution, chlorhexidine diacetate forms micelles and has a molar critical micellar concentration (CMC) of 0·010–0·011 at 25°. Similarly, the digluconate salt has a molar CMC of 0·0066. Above its CMC, the freely soluble digluconate salt solubilizes the less soluble diacetate salt. The formation of micelles does not affect the rate of hydrolysis of chlorhexidine to p-chloroaniline. It is suggested that the micelles formed by chlorhexidine resemble those formed by many dyes rather than those of colloidal surfactants. Equilibrium dialysis experiments show that 1·0 and 3·0% polysorbate 80 inactivates 37·5 and 70·0% respectively of the chlorhexidine in a 0·10% solution of the diacetate salt.

The colloidal properties of chlorhexidine and its interaction with some macromolecules.

https://sites.cardiff.ac.uk/ukcxl/files/2013/11/Enhancement-of-corneal-permeation-of-riboflavin-5-phosphate-through-vitamin-E-TPGS-A-promising-approach-in-corneal-trans-epithelial-cross-linking-treatment.pdf

Enhancement of corneal permeation of riboflavin-5'-phosphate through vitamin E TPGS: a promising approach in corneal trans-epithelial cross linking treatment.

Solubility of ionic surfactants in water have been found to increase with added amount of nonionic hydrophilic polymers when both are capable of forming watersoluble complexes. Experiments were carried out with sodium hexadecyl sulfate (SHS) and hexadecyl amine hydrochloride (HAC) below theKrafft points of the respective surfactants. The solubility increment of the surfactants brought about by the polymers depends upon the kind of polymers, their molecular weight, concentration and temperature. The results have been interpreted on the basis of the amount of surfactants bound to the polymers and by the properties of the polymer-surfactant complexes formed. It is noteworthy that the anionic surfactant (SHS) can be bound to polymers much more extensively than the cationic surfactant (HAC).

Solubilities of ionic surfactants in aqueous polymer solutions

An aqueous liquid preparation of the present invention containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof, an alkyl aryl polyether alcohol type polymer such as tyloxapol, or a polyethylene glycol fatty acid ester such as polyethylene glycol monostearate is stable. Since even in the case where a preservative is incorporated into said aqueous liquid preparation, the preservative exhibits a sufficient preservative effect for a long time, said aqueous liquid preparation in the form of an eye drop is useful for the treatment of blepharitis, conjunctivitis, scleritis, and postoperative inflammation. Also, the aqueous liquid preparation of the present invention in the form of a nasal drop is useful for the treatment of allergic rhinitis and inflammatory rhinitis (e.g. chronic rhinitis, hypertrophic rhinitis, nasal polyp, etc.).

Aqueous liquid preparation containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid

Equilibrium dialysis studies utilizing a semipermeable nylon membrane indicate a high degree of association and accompanying inhibition of quaternary ammonium germicides such as cetylpyridinium chloride and benzalkonium chloride with nonionic surfactants such as Tween 80. Cetylpyridinium chloride was also found to bind to methylcellulose, but not to PVP or Polyox. Benzalkonium chloride was not bound to methylcellulose, PVP, or Polyox under the conditions of this study.

Patrick P. Deluca

Papers

Interaction of Preservatives With Macromolecules IV: Binding of Quaternary Ammonium Compounds by Nonionic Agents