Application of advanced thermal analysis for characterization of crystalline and amorphous phases of carvedilol

Marcin Skotnicki; Anna Czerniecka-Kubicka; Grace Neilsen; Brian F Woodfield; Marek Pyda

doi:10.1016/j.jpba.2022.114822

Application of advanced thermal analysis for characterization of crystalline and amorphous phases of carvedilol

J Pharm Biomed Anal. 2022 Aug 5:217:114822. doi: 10.1016/j.jpba.2022.114822. Epub 2022 May 7.

Authors

Marcin Skotnicki¹, Anna Czerniecka-Kubicka², Grace Neilsen³, Brian F Woodfield³, Marek Pyda⁴

Affiliations

¹ Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 60-780 Poznan, Poland. Electronic address: marcskot@ump.edu.pl.
² Department of Experimental and Clinical Pharmacology, Medical College of Rzeszow University, The University of Rzeszow, 35-310 Rzeszow, Poland; Interdyscyplinarny Center Preclinical and Clinical Research, The University of Rzeszow, 36-100 Werynia, Poland.
³ Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
⁴ Department of Chemistry, Rzeszow University of Technology, 35-959 Rzeszow, Poland.

PMID: 35550491
DOI: 10.1016/j.jpba.2022.114822

Abstract

The thermal behaviour of crystalline and amorphous carvedilol (CAR) phases was studied by advanced thermal analysis using Quantum Design Physical Property Measurement System and Differential Scanning Calorimetry. Theoretical functions describing crystalline carvedilol heat capacity at low temperatures and the Debye-Einstein function for high temperatures were obtained. Based on the experimental heat capacity values, solid and liquid baselines were established, and the state functions (H, S, G) for solid and liquid states were calculated. A comprehensive characterization of melting and glass transition processes was obtained. CAR is easily amorphizable by cooling the liquid. The residual entropy, which quantifies the extent of frozen-in disorder in the amorphous solid, for glassy CAR was estimated as 51 J·mol^-1·K^-1. The Kauzmann temperature (T_K) was estimated based on enthalpy and entropy. Molecular motions in the amorphous phase were also studied. The activation energy for structural relaxation (E_a = 539 kJ·mol^-1) and fragility parameter (m = 91) were obtained from the non-isothermal physical ageing. The isothermal physical ageing kinetics of amorphous CAR was studied by applying Kohlrausch-Williams-Watts (KWW) model. The mean molecular relaxation time constant (τ^KWW = 117 min) and relaxation constant (β^KWW = 0.33) were obtained. CAR was classified as a fragile glass-former. Furthermore, τ^KWW constant for samples aged at 303.15 K is very low, thus, the physical ageing will occur during the short- and long-term storage of amorphous CAR, potentially changing its physicochemical properties during the ageing process. However, the results of molecular mobility studies (high molecular motions) show that the relationship between molecular motions in a glassy solid and its tendency to crystallization does not seem to follow an expected pattern, i.e., no crystallization occurred by thermal treatment of glassy, supercooled liquid and liquid phases of CAR as one would expect. Modern calorimetry and quantitative thermal analysis provided the fundamental kinetic and thermodynamic information about the crystalline and amorphous states of CAR.

Keywords: Amorphous pharmaceuticals; Carvedilol; Differential scanning calorimetry; Heat capacity; Physical ageing; State functions.

MeSH terms

Calorimetry, Differential Scanning
Carvedilol*
Crystallization
Phase Transition
Thermodynamics

Substances

Carvedilol