Abstract
In order to clarify the mechanism of coprecipitation of the drug with polyvinylpyrrolidone (PVP), the temperature of absolute ethanol solution saturated with various drugs, was lowered at a constant rate from 50°to 10°, and the inhibitory effect of PVP on the crystallization of drugs was examined. The interaction of these drugs with PVP in absolute ethanol was also investigated and compared with the effect of PVP on the crystallization of drugs. The crystallization of sulfamethizole and sulfisoxazole which interacted strongly with PVP were strongly inhibited and/or retarded over the temperature range studied. PVP retarded, but did not inhibit the crystallization of sulfamerazine. Crystallization of caffeine and nalidixic acid, which interacted poorly with PVP, was not affected by PVP. N-Vinyl-2-pyrrolidone, the monomer unit of PVP molecule, did not affect the crystallization of sulfisoxazole. PVP K-30 showed the strongest effect among K-15, K-30 and K-90. Polyethylene glycol and polysorbate 80 did not affect the crystallization of sulfisoxazole. Sulfamethizole and sulfisoxazole formed coprecipitates with PVP, whereas caffeine and nalidixic acid did not form coprecipitates with PVP. Sulfamerazine on the other hand did not form well-defined coprecipitate with equal weight ratio of PVP. The mechanism of coprecipitation of drug with PVP may be the inhibition of crystallization of drug by PVP, when the solution containing both drug and PVP is evaporated. The drug loses its crystal structure in PVP matrix. Coprecipitation does not occur when PVP does not inhibit the crystallization of drug.
