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Amorphous drug nanosuspensions. 1. Inhibition of Ostwald ripening
Lennart Lindfors1, Pia Skantze, Urban Skantze
1Pharmaceutical and Analytical R & D, Experimental Formulations, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. lennart.lindfors@astrazeneca.com
Abstract:
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 chi using the Bragg-Williams theory, in which single phase mixtures are obtained for chi < 2. The chi 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.
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