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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.

Amorphous drug nanosuspensions are prone to particle growth due to Ostwald ripening. By incorporating a second component of extremely low aqueous solubility, Ostwald ripening can be inhibited. These studies indicate that to inhibit ripening, the drug/inhibitor mixture (in the particles) must form a single phase. The drug/inhibitor mixture can be characterized by the interaction parameter χ using the Bragg-Williams theory, in which single phase mixtures are obtained for χ < 2. The χ parameter can be calculated from the (crystalline) solubility of the drug in the inhibitor, provided the inhibitor is a liquid, and the melting entropy and temperature of the drug.