Abstract
The permeation of chlorothiazide through the in vitro everted rat intestine was investigated from dilute, saturated and supersaturated solutions in the presence and absence of PVP. Although chlorothiazide clearance was lower than that of either hydrochlorothiazide or salicylic acid, the high dose to solubility ratio rather than excessive membrane impermeability, seemed the primary factor limiting chlorothiazide absorption. Reduced chlorothiazide membrane transport from dilute solutions containing PVP and enhanced dissolution from a drug:PVP (1:2) mechanical mixure were observed and could be explained by the formation of a soluble complex in solution. Chlorothiazide transport rates, from systems supersaturated relative to crystalline chlorothiazide, were enhanced in the presence of PVP. This effect together with increased dissolution from a chlorothiazide:PVP (1:2) coprecipitate were consistent with the ability of PVP to inhibit drug crystallization.
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