Solute and solvent effects on the thermorheological properties of poly(oxyethylene)-poly(oxypropylene) block copolymers: Implications for pharmaceutical dosage form design

Despite their widespread use as platforms for topical drug delivery systems, there is a relative lack of information concerning the thermorheological and viscoelastic properties of poloxamer systems and the effects of formulation components on these properties. To address this deficit, we examined the effects of the poloxamer concentration (25 and 35% w/w), molecular weight blend (poloxamer 407 and poloxamer 188), cosolvents (ethanol, propylene glycol, and glycerol), and presence of inorganic and organic electrolytes (sodium chloride and tetracaine hydrochloride, respectively) on these properties. The rheological properties were examined with a rheometer (4-cm-diameter, stainless steel, parallel-plate geometry) in either thermal sweep (0.5 Hz) or frequency sweep (0.01-1.0 Hz and 37degreesC) modes. Increasing the poloxamer concentration increased the elasticity [i.e., increased the storage modulus (G') and reduced the loss tangent (tan 5)] and reduced the sol-gel transition temperature (T,,) of all the formulations. Decreasing the ratio (407:188) increased T-m and reduced the elasticity of all the formulations. Increasing the concentration of ethanol, propylene glycol, or glycerol in the solvent reduced T-m. The presence of ethanol reduced G' and increased tan 8 in a concentration-dependent fashion, whereas the viscoelastic properties of the poloxamers were more tolerant of glycerol (in particular) and propylene glycol. The elasticity of the formulations containing up to 10% glycerol and 5% propylene glycol was increased with respect to their aqueous counterparts. The presence of sodium chloride reduced T-m and, at lower concentrations (1 and 3%), increased G' and reduced tan 5 for aqueous poloxamer systems. Conversely, the addition of a model therapeutic agent, tetracaine hydrochloride (5 and 7% w/w), significantly increased T. and altered the viscoelastic character of the poloxamer system, notably reducing G' and increasing the loss modulus and tan 8. Alterations in the viscoelastic and thermorheological properties of aqueous poloxamer systems will have implications for their clinical performance. This study, therefore, has highlighted the need for the rational selection of components in the formulation of poloxamer systems as platforms for topical drug delivery. (C) 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1016 -1026, 2003.