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Figure 8.28 Dissolution of sodium chloride from tablets coated with hydroxypropylmethylcellulose (O), a vinyl polymer (•) and zein (©) with glycerin as an additive, and the same polymers with diethyl phthalate as additive (□, , and □ respectively).

Reproduced from O. Laguna etal., Ann. Pharm. Franc., 33, 235 (1975).

are useful in determining which factors may be altered to change the measured release rate of drug. Higuchi11 proposed the following equation for the amount of drug, Q, released per unit area of tablet surface in time t, from an insoluble matrix:

D is the diffusion coefficient of the drug in the release medium, Cs is the solubility of drug in the medium, e is the porosity of the matrix, t is the tortuosity of the matrix, and A is the total amount of drug in the matrix per unit volume.

If the same matrix is saturated with a solution of the drug (as in medicated soft contact lenses, see Chapter 9) the appropriate equation becomes, if C0 is the concentration of drug solution:

That is, for a given drug in a given matrix, Q ^ t1/2. The more porous the matrix the more co n m co m n

Time

Figure 8.29 (a) Drug delivery from a matrix delivery device showing diagrammatically the depletion of drug from the system and the release of the drug. (b) Release from a typical reservoir system with a membrane controlling release from the internal store of drug. (c) Illustrating release from (i) a bulk-eroding system and (ii) a surface-eroding system.

After Lisa Brannon-Peppas, Polymers in Controlled Drug Delivery, Medical Plastics and Biomaterials, 1997(Nov.), p. 34.

rapid the release. The more tortuous the pores the longer the path for diffusing molecules, thus the lower is Q. More-soluble drugs diffuse more quickly form the matrix.

The extension of these equation to hydro-philic matrices is difficult because the conditions in a hydrophilic matrix change with time as water penetrates into it. If the polymer does not dissolve but simply swells and if the drug has not completely dissolved in the incoming solvent, diffusion of drug commences from a saturated solution through the gel layer, and

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