Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate

Abstract

The proposed study examined the characterization and stability of solid-state amorphous imatinib mesylate (IM) after 15 months under controlled relative humidity (60 ± 5%) and temperature (25 ± 2 °C) conditions. After 2 weeks, and 1, 3, 6, and 15 months, the samples were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffractometry (XRPD), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Additionally, the amorphous form of imatinib mesylate was obtained via supercooling of the melt in a DSC apparatus, and aged at various temperatures (3, 15, 25 and 30 °C) and time periods (1–16 h). Glass transition and enthalpy relaxation were used to calculate molecular-relaxation-time parameters. The Kohlrausch–Williams–Watts (KWW) equation was applied to fit the experimental enthalpy-relaxation data. The mean molecular-relaxation-time constant (τ) increased with decreasing ageing temperature. The results showed a high stability of amorphous imatinib mesylate adequate to enable its use in solid dosage form.

Nanohydroxyapatite-Mediated Imatinib Delivery for Specific Anticancer Applications

“…Moreover, there have been no detected differences in spectra between the β-form (blue line, Figure 3 ) and amorphous (black line) form. Both spectra could be found due to broadened bands attributed to the amorphous IM, showed by Mucha et al [ 33 ].…”

“…Amorphous substances, compared to their crystalline forms, possess a more irregular shape as well as higher internal energy and specific volumes, improving the dissolution and bioavailability of these compounds [ 33 ]. It means that the same drug could be used at a lower dose leading to a reduced risk of local side effects caused by unabsorbed materials and has a cost-saving effect.…”

“…However, if there are those that exhibit greater stability, they could constitute a potential novel drug product. One of them is amorphous imatinib (IM-4-[(4-Methyl-1-piperazinyl)methyl]- N -[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino] phenyl]benzamide methanesulfonate) which has confirmed long-term stability [ 33 ]. imatinib (IM) is tyrosine-kinase inhibitor use in certain types of cancer treatments, e.g., myeloid leukemia [ 34 ], gastrointestinal stromal tumors [ 35 ], and also in the other malignancies involving the expression of tyrosine kinase [ 30 ].…”

An Investigation of the Impact of Precipitation Temperature and Filter Cake Thickness on the Physical Stability of Amorphous Solids: A Case Study

“…This phenomenon occurs because higher temperatures enhance molecular mobility, promoting a propensity toward crystallization. Consequently, precise temperature control during precipitation was crucial to maintain the amorphous state [34]. Moreover, below the T g , molecular mobility and the subsequent molecular rearrangements that could lead to nucleation and crystal growth were minimized [35].…”