Amorphous Drug Nanosuspensions. 2. Experimental Determination of Bulk Monomer Concentrations

A simple turbidimetric method was developed to measure the bulk concentration of drug in nanosuspensions. The bulk concentrations measured were in the range from 1 μM to 1 mM. The accuracy of the method was checked by determination of the bulk concentration of crystalline nanosuspensions, i.e., the crystalline solubility, which compared favorably to solubilities measured by a conventional method. Results obtained for amorphous nanosuspensions agreed with predictions using a theory describing the relative solubility between a supercooled liquid and a crystal. Further, it was found that the bulk concentration in Ostwald ripening inhibited amorphous nanosuspensions and could be lowered by incorporation of higher amounts of the inhibitor, in agreement with predictions using the Bragg−Williams theory of nonideal solutions.