j. Soc. Cosmet. Chem., 31,107-121 (May/June 1980) Effect of surfactant polyoxyethylene chain length on flocculation of local anesthetic suspensions WIE-CHI LIAO, Present address, Schering-Plough Corp., 86 Orange St. Bloomfield, N.J. 07003 and JOEL L. ZATZ, Rutgers College of Pharmacy, P.O. Box 789, Piscataway, N.J. 08854. Received November 9, 1979. Presented at the Society of Cosmetic Chemists Annual Scientific Meeting, December 6-7, 1979, New York, New York. Synopsis The EFFECT of nonionic SURFACTANTS on structure in aqueous SUSPENSIONS of BENZOCAINE and BUTAMBEN was studied. FLOCCULATION, evaluated by sedimentation, viscosity and refiltration techniques, was a function of particle size, surfactant concentration and polyoxyethylene chain length. Factors in flocculation-deflocculation behavior included completeness of wetting, surfactant phase separation and the properties of the adsorbed surfactant layer on the particle surface. Structural properties of the suspensions were also influenced by storage conditions after manufacture. ACKNOWLEDGEMENT The support of a Society of Cosmetic Chemists' grant to Wei-Chi Liao is gratefully acknowledged. INTRODUCTION One of the most difficult problems encountered in the formulation of cosmetic suspensions is that of caking. A caked suspension results from sedimentation of suspended particles into a hard, compact mass at the bottom of the container. Such a suspension cannot be redispersed by shaking to achieve a uniform system and is unsuitable as a cosmetic product. Basically, three approaches have been employed to produce physically stable suspensions: colloidal dispersion of solid particles, structured vehicle and controlled flocculation. A colloidally stable dispersion of a drug, the oldest method attempted, is based on the machanism of Brownian diffusion to keep the particles suspended in the medium. Dispersing agents are added to slow down the particle aggregation process (1) and 107

108 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS suspending agents can be used to adjust the medium viscosity (2). However, particies larger than colloidal size will still eventually sediment and possibly cake. The second approach uses a structured vehicle. The particles are dispersed in a vehicle whose viscosity approaches an infinite value under low shear, as at storage. Gums and other polymers that impart plastic and thixotropic flow properties to the suspension are needed when this approach is chosen (3). Perhaps the most widely used approach to prevent caking is the controlled fioccula- tion of suspended particles induced by the addition of electrolytes, polymers and other additives (4). A fiocculated suspension contains a network of loosely aggregated particles held together by Van der Waals' forces or interparticle bridges. Sedimenta- tion results in systems with a voluminous, porous sediment that is easily redispersed to yield a homogeneous suspension. Suspensions of this type exhibit good shelf life stability. Surfactants, both ionic and nonionic, are widely used for the purpose of wetting hydrophobic powders to be dispersed into aqueous suspension. Although it is known that the flocculation state of suspended particles can be affected by surfactants (4), little detailed work in this area has been reported. In a recent study, the adsorption of nonionic polyethoxylated octyl- and nonylphenols of sulfathiazole and naphthalene in relation to flocculation was investigated (5). It was found that surfactants with longer hydrophilic chain length improved the fiocculation state of sulfathiazole, but there was very little significance of hydrophilic chain length on naphthalene. In the present study, two local anesthetics, benzocaine and butamben, were used as model compounds to investigate the effect of surfactants on suspension flocculation. A homologous series of ployoxyethylene nonylphenols was studied in order to assess the effect of polyoxyethylene chain length on suspension properties. Flocculation was measured by three different techniques and adsorption studies were conducted as an aid in determining flocculation mechanism. EXPERIMENTAL MATERIALS Benzocaine (N.F. powder, Ruger Chemical Inc., Irvington, NJ.) and butamben (reagent, powder, MC&B Co., East Rutherford, N.J.) were the solid drugs studied. The nonionic surfactants, polyoxyethylene nonylphenols (GAF Co., N.Y., N.Y.), were used as received. Water used to prepare suspensions was deionized first by passing through two ion exchange columns and then distilled in an all glass still. SURFACTANT SOLUTIONS Surfactant solutions were prepared on the molar basis. Molecular weights obtained from the average hydrophilic chain length were used to calculate the molar concentra- tion. Surface tensions were measured by the Welhelmy plate method using a Rosano surface tensiometer (Pacific Scientific Co., Newark, NJ.). Water was used as a standard.