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been proposed as burn wound coverings to provide a film with the appropriate strength and physical properties.9

Crosslinked dextran gels are insoluble hydro-philic gels that can be partially depolymerised to the required molecular weight. The gel is produced in a bead shape; the degree of crosslinking determines the water uptake and pore size. Dextranomer (Debrisan) is a cross-linked dextran with pores large enough to allow substances with a molecular weight of less than 1000 to enter the beads. Each gram of beads abstracts approximately 4 cm3 of fluid. Applied to the surface of secreting wounds, dextranomer removes by suction various exu-dates that tend to impede tissue repair, while leaving behind high molecular weight materials such as plasma proteins and fibrinogen.

8.4.10 Polymer crystallinity

Polymers form perfect crystals with difficulty simply because of the low probability of arranging the chains in regular fashion, especially at high molecular weights. Advantage can be taken of defects in crystals in the preparation of microcrystals. Microcrystalline cellulose (Avicel) is prepared by disruption of larger crystals. It is used as a tablet excipient and as a binder-disintegrant. Dispersed in water it forms colloidal gels, and it can be used to form heat-stable o/w emulsions. Spheroidised forms of microcrystalline cellulose with accurately controlled diameters can be prepared and drugs can be incorporated during preparation. The concept of crystallinity is potentially important when considering polymer membranes, as discussed below.

8.5 Water-insoluble polymers and polymer membranes

In defining the properties of polymers for drug formulation, certain characteristics are important. Obviously molecular weight and molecular weight distribution must be known, as these affect solvent penetration and crystal-linity. The functionality of the polymer is best described by a series of parameters such as

• Glass transition temperature, T

• Tensile strength

• Diffusion coefficient

• Hardness (crystallinity)

• Solubility

Crystallinity defines several features of polymers: rigidity, fluidity, the resistance to diffusion of small molecules in the polymer, and degradation.

In hydrogels T can be measured and is a measure of polymer structure, crosslinking density, solvent content and polymer-solvent interactions, as can be seen from Table 8.6.

8.5.1 Permeability of polymers

Hydrophobic polymers also play an important role in pharmacy. When these materials are used as membranes, containers or tubing material, their surfaces may come into contact law (see Section 3.6, equation (3.90)): dc

Presence of flexible groups in main chain Y Bulky, inflexible side-chains

Flexible side-chains Y

Increase in main chain polarity 9

Increase in crosslinking 9

Plasticiser content Y

Presence of flexible groups in main chain Y Bulky, inflexible side-chains

Flexible side-chains Y

Increase in main chain polarity 9

Increase in crosslinking 9

Plasticiser content Y

with solutions. The surfaces of insoluble polymers are not as inert as might be thought. The interaction of drugs and preservatives with plastics depends on the structure of the polymer and on the affinity of the compound for the plastic. The latter is determined by the degree of crystallinity of the polymer, as permeability is a function of the degree of amorphous content of the polymer. The crystalline regions of the solid polymer present an impenetrable barrier to the movement of most molecules. Diffusing molecules thus have to circumnavigate the crystalline islands, which act as obstructions. The greater the volume fraction of crystalline material (pc) the slower the movement of molecules.

Diffusion

Diffusion in nonporous solid polymer is of course a more difficult process than in a fluid because of the necessity for the movement of polymer chains to allow passage of the drug molecule, and it is therefore slower. The equation which governs the process is Fick's first where J is the flux, D is the diffusion coefficient of the drug in the membrane, and dc/dx is the concentration gradient across the membrane. If the membrane is of thickness l, and Àc represents the difference in solution concentration of drug at the two faces of membrane,

where K is the distribution coefficient of the permeant towards the polymer. Therefore alteration of polymer/membrane thickness, coupled with appropriate choice of polymer, can give rise to the desired flux. Within a given polymer, permeability is a function of the degree of crystallinity, itself a function of polymer molecular weight. If P is the permeability of drug in a partially crystalline polymer (see Fig. 8.24), the volume fraction of the crystalline regions being 0c, and Pa is the permeability in an amorphous sample, then

0 0

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