An example of application of a mixture design with constraints to a pharmaceutical formulation

The aim of this tutorial is to show the application of a mixture experimental design to a problem of pharmaceutical formulation. A gel, based on poloxamer 407, useful for topical administration of tolfenamic acid, a potent anti-inflammatory drug very poorly soluble in water, has been prepared, and a mixture experimental design was used to study the influence of the components on the viscosity of the formulation. Its application allowed to identify a critical boundary, separating semisolid formulations from liquid ones, within a narrow interval of concentrations of the components, and to estimate their effects on the viscosity of the preparation.

[1]  Alfonso R. Gennaro,et al.  Remington:the science and practice of pharmacy , 1995 .

[2]  B. W. Barry,et al.  Sensory assessment of spreadability of hydrophilic topical preparations. , 1973, Journal of pharmaceutical sciences.

[3]  H. Choi,et al.  Effect of additives on the physicochemical properties of liquid suppository bases. , 1999, International journal of pharmaceutics.

[4]  S. B. Pedersen.  Biopharmaceutical aspects of tolfenamic acid. , 1994, Pharmacology & toxicology.

[5]  M. Takada,et al.  Pluronic F-127 gels as a novel vehicle for rectal administration of indomethacin. , 1986, Chemical & pharmaceutical bulletin.

[6]  H. Jun,et al.  Release rates of ketoprofen from poloxamer gels in a membraneless diffusion cell. , 1991, Journal of pharmaceutical sciences.

[7]  I. R. Schmolka.  Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. , 1972, Journal of biomedical materials research.

[8]  Diana Wang,et al.  Salt effects on the diffusion and release rate of propranolol from poloxamer 407 gels , 1998 .

[9]  Susan C. Miller,et al.  Effect of poloxamer 407 gel on the miotic activity of pilocarpine nitrate in rabbits , 1982 .

[10]  N. Pandit,et al.  Loss of gelation ability of Pluronic® F127 in the presence of some salts , 1996 .

[11]  J. Hadgraft,et al.  Topical Application of Penetration Enhancers to the Skin of Nude Mice: a Histopathological Study , 1989, The Journal of pharmacy and pharmacology.

[12]  T. A. Hatton,et al.  Poly(ethylene oxide)-poly(propylene oxide )-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling , 1995 .

[13]  H. Jun,et al.  Physicochemical and release studies of naproxen in poloxamer gels , 1996 .

[14]  Woo Y. Lee,et al.  Skin Permeation of Flurbiprofen through Excised Rat Skin from Poloxamer 407 Gel , 1994 .

[15]  J. Cornell.  Experiments with Mixtures: Designs, Models and the Analysis of Mixture Data , 1982 .