文摘
Nucleation kinetics of eflucimibe polymorphs have been investigated in ethanol and n-heptane mixture. The two eflucimibe polymorphs, A and B, crystallize concomitantly for a wide range of operating conditions. The effects of supersaturation on the nucleation rates of the two existing polymorphs were analyzed. The relative nucleation rates of A and B form determine the nature of the polymorph obtained at the end of the crystallization process. The determination of the induction time for polymorphs allows to determine the crystal−solution interfacial energy for the two forms: γsl(A) = 5.17, γsl(B) = 4.23 mJ m−2. The values obtained were compared with the ones obtained from direct methods: by contact angle measurement (7.32 mJ m−2) and is significantly lower than values predicted by equations derived from simplified theories (15 mJ m−2). From induction time measurements, the nucleation rate of each polymorph was determined. The evolution of the nucleation rate with supersaturation allows the determination of the occurrence domain of each polymorph. It was found experimentally, at low (S < 1.8) and high supersaturation (S > 2.7), that the polymorphic powder composition is in agreement with the occurrence domains determined from nucleation rates. However, at intermediate supersaturation, due to the nearly equivalent structure of the two polymorphs, the occurrence domain of concomitant nucleation is wider than expected.
