Assessment of the origin and stability of Nifedipine polymorph IV by differential scanning calorimetry (DSC)

Andres-Tome, I. and Antonijevic, Milan D. (2009) Assessment of the origin and stability of Nifedipine polymorph IV by differential scanning calorimetry (DSC). The AAPS Journal, 11 (Suppl. 2). ISSN 1550-7416

Abstract

Purpose. To examine the thermal transition(s) between different polymorphic forms of Nifedipine and to define experimental
conditions that lead to the generation of polymorph IV.
Methods. Experiments were performed using a DSC 823e (Mettler Toledo). Nifedipine exists in four polymorphic forms, as
well as an amorphous state. Examination of Nifedipine was conducted using the following method(s): cycle 1: 25ºC to 190ºC,
190ºC to 25ºC (formation of amorphous Nifedipine); cycle 2: 25ºC to X (60,70,80...150ºC), X to 25ºC; cycle 3: 25ºC to
190ºC and holding isothermally for 5 min between cycles (heating/cooling rate of 10ºC/min).
Results. The amorphous state Nifedipine can sustain heating up to 90ºC without significant changes in its composition. Cycle
2 of amorphous material heated up to 90ºC shows only the glass transition at ~44ºC. In cycle 3 of the same material, a glass
transition has been recorded at ~44ºC, followed by two exotherms (~100 and ~115ºC (crystallisation of polymorph III and II,
respectively) and an endotherm (169ºC (melting of polymorphs I/II)). Samples that have been heated to temperatures between
100ºC and 120ºC in the second cycle showed a glass transition at ~44ºC and an additional exotherm at ~95ºC (crystallisation
of polymorph III) on cooling a exotherm was observed at ~40ºC (crystallisation of polymorph IV). The same material
showed no glass transition in cycle 3 but an endotherm at around 62ºC (melting of polymorph IV) an exotherm (~98ºC) and
an endotherm (169ºC) melting of polymorph I/II. Heating the sample to a temperatures greater than 130ºC in cycle two
results in a glass transition at ~44ºC, and two exotherms at ~102 and 125ºC (crystallisation of polymorphs III and I,
respectively).
Conclusions. DSC data suggests that polymorph IV can only be produced from amorphous or polymorph III samples. The
presence of polymorph I or II drives the conversion of the less stable polymorphic form IV into the most stable form, I.
Although form IV of Nifedipine can easily be created, following defined experimental conditions, it may only coexist with
amorphous or polymorph III states. When polymorphs I and II are present in the sample polymorph IV cannot be detected.

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