The Importance of Fine Particles in Pharmacy

THE IMPORTANCE OF FINE PARTICLES IN PHARMACY

Although fine particles can be produced directly by controlled precipitation, crystallization, or drying a fine spray of solution, in many cases the material is powdered in some kind of mill. From our point of view, the most important result of this operation is the increase in the surface area of a given weight of the powder and its influence on diffusional processes. A cube of side 0.01 m has a surface area of 6 x 10^-4 m². If, by some ideal size reduction process, this cube was divided into cubes of side 0.001 m, we should have a thousand particles each with a surface area of 6 x 10^-6 m² and a total surface area of 6 x 10^-3 m². A tenfold increase in surface area has been given by a tenfold decrease in particle size. Generalizing, we may say that the surface area is inversely proportional to the particle size assuming that the shape of the particles remains the same.

The rate of most chemical and physical reactions involving solids and liquids is greatly influenced by the area of interfacial contact. In chemical reactions, a reagent must diffuse toward the surface of the solid and the reaction products away, a procedure that depends, among other things, on the area between solid and liquid. The effect of particle size on dissolution rate exem-plifies another aspect of diffusion that is of importance to the pharmacist. Most commonly, drugs are taken orally in the form of solid particles, and absorption, which is usually rapid, must be preceded by dissolution. A full discussion of the role of particle size in oral, parenteral, and topical therapies may be found in reviews (Newman and Axon, 1961; Wagner, 1961).

The rate at which fine chemicals or drugs are extracted from a vegetable source is increased by an increase of surface area. Reduction of particle size increases the area available for transfer of materials and decreases the distance over which solvent and solute must diffuse and has a marked effect on the drying of porous materials.

Other effects, not based on diffusion and its dependence on surface area, are found in mixing and various formulation requirements. If we withdraw a sample from a mixture of powders, it is unlikely to contain exactly the correct proportion of ingredients. However, the larger the number of particles in the sample, the closer the sample will represent the overall proportions of the mixture. We can therefore increase the accuracy of the sample, which might eventually form a tablet or a capsule, by increasing the number of particles it contains, that is, reducing the particle size of the components of the mix. Since difference of particle size will promote segregation, the components should be produced with a similar particle size distribution.

Formulation requirements often dictate the use of fine particles. Impal-pability and spreading are required of dusting and cosmetic powders. Particles of 3.5 x 10^-5 to 4.0 x 10^-5 m can be detected as single particles when applied to the skin and may give the impression of grittiness. Such powders should, in general, be finer than 3.0 x 10^-5 m. When powders are tinted, the particle size of powder and pigment affects the final color. In tabletting, careful size reduction of imperfect tablets provides a material suitable for compression. The flow properties of suspensions of high disperse phase concentration are affected by particle size and size distribution. At a given disperse phase concentration, decrease of particle size gives an increase in viscosity, while a broadening of particle size distribution yields a decrease in viscosity. Sedimentation is a function of particle size.

Numerous examples have been quoted to stress the importance of fine particles in pharmacy. Milling or grinding offers a method by which these particles may be produced, size classification gives a means, where applicable, of selecting a desired fraction or of removing oversize or undersize particles, and size analysis provides the analytical tool by which these operations may be assessed and controlled.