Amorphous drug nanosuspensions. 1. Inhibition of Ostwald ripening.
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.
Lindfors
Lennart
L
Pharmaceutical and Analytical R & D, Experimental Formulations, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. lennart.lindfors@astrazeneca.com
Skantze
Pia
P
Skantze
Urban
U
Rasmusson
Mikael
M
Zackrisson
Anna
A
Olsson
Ulf
U
D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D036103:Nanotechnology; D009543:Nifedipine / Q000737:chemistry*; D012995:Solubility
D002121:Calcium Channel Blockers; D009543:Nifedipine