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Crystallization or amorphization? Defining the dominant process using thermal analysis

Crystallization or amorphization? Defining the dominant process using thermal analysis

Nneka, Odiaka, Jordan, Daniel, Owusu-Ware, Samuel K. and Antonijevic, Milan ORCID: 0000-0002-5847-7886 (2015) Crystallization or amorphization? Defining the dominant process using thermal analysis. In: CEEC-TAC3, 25-28 August 2015, Ljubljana, Slovenia.

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Co-crystallization and co-amorphization are considered key methods [1, 2] in overcoming challenges of the ever increasing proportion of APIs, in the pharmaceutical industry pipeline, with low solubility in aqueous media. Furthermore, it is desirable that the solid forms of the APIs are engineered by means of green chemistry. As such generation of co-crystals and co-amorphous systems using methods such as hot-melt extrusion (HME) are being increasingly investigated [1]. During melt extrusion, for example, the cooling of the molten APIs/formulation can result in four possibilities: (1) the compounds convert into their unique crystal form(s), (2) become kinetically trapped at different rates resulting in two distinct amorphous phases with different Tg values, (3) generation of a single crystalline form with a crystal lattice containing each compound (co-crystal) or (4) generation of a single amorphous phase with a single Tg (co-amorphous). Herein we investigate which process dominates upon cooling a molten mixture (1:2, 1.1 and 2:1 molar ratios) of two miscible compounds (Pindolol (PD) and Acebutolol (AC), respectively) - one with strong crystallization tendency (PD) and the other with a strong glass forming tendency (AC) - at different scan rates (1 to 40°C/min) by means of DSC.
Initial results show that mixtures of the two compounds generate eutectics (Fig.1a) and upon co-melting and subsequent cooling a single amorphous phase (co-amorphous) is detected at all the molar ratios studied (Fig. 1b), at all cooling rates. However, when the ratio of the PD is increased to 2:1 (Fig.1b), small amounts of crystals are generated which seeds the rubbery amorphous phase after the Tg resulting in crystallization at 88 ± 1°C (onset) followed by a melt at 143°C (onset). The results show that amorphization dominates over crystallization when two miscible compounds are co-melted and cooled and this is independent of the cooling rate. Furthermore this study demonstrates the use of DSC to screen co-formers for the generation of co-crystal or co-amorphous solids using HME.

Item Type: Conference or Conference Paper (Poster)
Additional Information: Poster Session 1: Theory & Methods, Kinetics & Catalysis, Fuels & Biofuels, Energetics and Applied Thermal Engineering
Uncontrolled Keywords: Amorphization, Crystallization, Co-amorphization, co-crystallization, Pindolol, Acebutolol
Faculty / School / Research Centre / Research Group: Faculty of Engineering & Science > School of Science (SCI)
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Last Modified: 20 Nov 2017 09:39

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