The effects of a model mucus system on the dissolution rate of tetracycline hydrochloride have been assessed. The model is unique in containing only the rheologically active fraction of the secretion which is a large glycoprotein. A solution of mucus glycoprotein reduced the dissolution rate of tetracycline hydrochloride compared to that in simple acid media although the rate reduction was not the same as that observed in solutions of other viscous agents at the same viscosity. The nature of the results suggests that this occurs as a result of two separate viscosity-related effects. First, the presence of the glycoprotein causes an increased resistance to diffusion but this is less than that expected from the bulk viscosity. In this respect, the mucin resembles other large hydrophillic polymers in having a low, so-called “effective” viscosity. Second, the high viscosity causes a hydrodynamic effect of an increased diffusion layer thickness the maximum value of which is limited by the geometry of the dissolution vessel. Mucus glycoprotein also reduced the dissolution rate and final drug concentration at neutral pH, due to an enhanced build up of crystals of free base on the dissolving solid. This behaviour was altered by the bile salts sodium cholate, deoxycholate and taurodeoxycholate in a manner which can he rationalized in terms of the respective pK a values.
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