Polymer Inhibition of Crystal Growth by Surface Poisoning

Controlling the rate of crystal growth from supersaturated solutions is a desirable capability in the pharmaceutical field. The biological absorption of poorly soluble drugs can be enhanced by inhibiting crystal growth and prolonging the duration of supersaturated solutions formed in vivo by dissolving supersaturating dosage forms. The use of polymeric additives to slow crystal growth is an emerging area of interest, yet the mechanisms of polymer inhibition are still being explored. In this study, the ability of a polymer to poison crystal growth and impact crystal morphology is assessed for felodipine crystallized from the amorphous material under different conditions. It was found that when polymers are present during crystal evolution from an amorphous solid exposed to water, they can impact the size and shape of the resulting crystals. This in turn influences the subsequent rate of crystal growth from supersaturated solutions. Therefore, when testing the ability of polymers to impact crystal growth, and the impact of crystal seeds on the rate of desupersaturation, the crystallization conditions, and treatment of the seed crystals should be carefully considered in order to better evaluate the de-supersaturation risk for supersaturating dosage forms.