NQR frequencies of anhydrous carbamazepine polymorphic phases

TL;DR

This study demonstrates that Nuclear Quadrupole Resonance (NQR) can rapidly identify different polymorphic forms of anhydrous carbamazepine, aiding pharmaceutical quality control by distinguishing therapeutically active and inactive phases.

Contribution

The paper introduces NQR as a quick, room-temperature method to differentiate polymorphic phases of carbamazepine, including the detection of characteristic frequencies for forms I and III.

Findings

NQR successfully characterized forms I and III of carbamazepine.

Characteristic NQR frequencies for forms I and III were identified.

Form II was not detected within the frequency range studied.

Abstract

In this work we propose the Nuclear Quadrupole Resonance (NQR) technique as an analytical method suitable for polymorphism detection in active parts (or active principles) of pharmaceuticals with high pharmacological risk. Samples of powder carbamazepine (5H-dibenz(b,f)-azepine-5-carboxamide) are studied. In its anhydrous state, this compound presents at least three different polymorphic forms: form III, the commercial one, form II, and form I. Of these, only form III possesses desirable therapeutic effects. By using the NQR technique, it was possible to characterize two of the three polymorphic phases (I and III) for anhydrous carbamazepine in few minutes at room temperature, detecting the characteristic frequencies of 14N nuclei (I=1) present in their chemical composition and in the frequency range 2.820-3.935 MHz. For form II, characteristic lines were not detected within this range of frequencies. The lines detected for form III are centered at the frequencies \nu_{1}^{III}=3.876 MHz, \nu_{2}^{III}=3.829 MHz, and \nu_{3}^{III}=2.909 MHz; and for form I centered at \nu_{1}^{I}=3.876 MHz, \nu_{2}^{I}=3.840 MHz, \nu_{3}^{I}=2.911 MHz, and \nu_{4}^{I}=2.830 MHz.