title: On formulating ophthalmic emulsions.
abstract: The formulation of dilute, transparent ophthalmic emulsions (eye drops) with long shelf lives is a challenge because of the tendency of the emulsion droplets to aggregate, particularly in the presence of the water-soluble polymers typically used in eye drops. While many functions of eye drops, such as lubricity and residence time in the eye, are promoted by high concentrations of high molecular weight water-soluble polymers, emulsified lipids and drugs aggregate in the eye drop bottle if the polymer concentration is above the critical flocculation concentration (CFC). The purpose is to develop a simple approach to predict the CFC for polymers based on information readily available in the literature. High molecular weight guar was hydrolyzed to give a series of guar samples spanning a wide range of average molecular weights. The CFC values and critical viscosity concentrations were measured as functions guar properties, using electrophoresis, dynamic light scattering and rheology measurements. The higher the guar molecular weight, the lower was the CFC, the maximum concentration that can be tolerated in the eye drop formulation. The guar CFC values were approximately equal to the overlap concentrations where guar molecules start to overlap in solution. We propose that the CFC can be estimated for any water-soluble polymer using the polymer molecular weight and the readily available Mark-Houwink parameters, thus providing a design rule for ophthalmic emulsions.
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada.
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Mafi
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada.
authors.forename: Cameron
authors.initials: C
authors.lastname: Gray
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada. Electronic address: peltonrh@mcmaster.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Pelton
authors.affiliation: Alcon Research, Ltd., 6201 South Freeway, Fort Worth, TX 76134-2099, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Ketelson
authors.affiliation: Alcon Research, Ltd., 11460 Johns Creek Parkway, Johns Creek, GA 30097, USA.
authors.forename: James
authors.initials: J
authors.lastname: Davis
mesh_terms: D002626:Chemistry, Pharmaceutical; D004586:Electrophoresis; D004655:Emulsions; D008027:Light; D008970:Molecular Weight; D009883:Ophthalmic Solutions; D012212:Rheology; D012542:Scattering, Radiation; D014783:Viscosity
chemical_list: D004655:Emulsions; D009883:Ophthalmic Solutions
keywords: Depletion flocculation; Emulsion stability; Eye drop formulation; Guar; Overlap concentration