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a Reproduced from C. F. Lerk etal., J. Pharm. Sci., 66, 1480 (1977).

forms, although this would not be necessarily a universal finding but one dependent on the orientation of the drug molecules in the crystal and the composition of the faces, as we have already seen with adipic acid. Thus, hydrophobic drugs have dual problems: they are not readily wetted, and even when wetted they have low solubility. On the other hand, because they are lipophilic, absorption across lipid membranes is facilitated.

1.7.1 Contact angle and wettability of solid surfaces

A representation of the several forces acting on a drop of liquid placed on a flat, solid surface is shown in Fig. 1.17(a). The surface tension of the solid, yS/A, will favour spreading of the liquid, but this is opposed by the solid-liquid interfacial tension, yS/L, and the horizontal component of the surface tension of the liquid yLjA in the plane of the solid surface, that is yLjA cos 0. Equating these forces gives

Equation (1.5) is generally referred to as Young's equation. The angle 0 is termed the contact angle. The condition for complete wetting of a solid surface is that the contact angle should be zero. This condition is fulfilled when the forces of attraction between the liquid and solid are equal to or greater than those between liquid and liquid.

The type of wetting in which a liquid spreads over the surface of the solid is referred to as spreading wetting. The tendency for spreading may be quantified in terms of the spreading coefficient S, where

If the contact angle is larger than 0°, the term (cos 0 - 1) will be negative, as will the value of S. The condition for complete, spontaneous wetting is thus a zero value for the contact angle.

1.7.2 Wettability of powders

When a solid is immersed in a liquid, the initial wetting process is referred to as immer-sional wetting. The effectiveness of immer-sional wetting may be related to the contact angle that the solid makes with the liquid-air interface (see Fig. 1.17b). The condition for complete immersion of the solid in the liquid is that there should be a decrease in surface free energy as a result of the immersion process. Once the solid is submerged in the liquid, the process of spreading wetting (see previous section) becomes important.

Table 1.10 gives the contact angles of a series of pharmaceutical powders. These values were determined using compacts of the powder (produced by compressing the powder in a large-diameter tablet die) and a saturated aqueous solution of each compound as the test liquid. Many of the powders are slightly hydrophobic (for example, indometacin and stearic acid), or even strongly hydrophobic (for example, magnesium stearate, phenyl-butazone and chloramphenicol palmitate). Formulation of these drugs as suspensions (for example, Chloramphenicol Palmitate Oral Suspension USP) presents wetting problems. Table 1.10 shows that 0 can be affected by the crystallographic structure, as for chloram-phenicol palmitate. Surface modification or changes in crystal structure are clearly not routine methods of lowering the contact angle

Table 1.10 Contact angles of some pharmaceutical powders0

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