Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

Abstract

Mirtazapine is an atypical antidepressant used in the management of insomnia, post-traumatic stress disorder, anxiety or panic disorder, obsessive–compulsive disorder and migraines. It is used worldwide in pharmaceutical formulations alongside various excipients in its hemihydrate form. The objective of the study was the compatibility evaluation between MRTHH and ten pharmaceutical excipients. The presence of incompatibilities between the API and the selected excipients was evaluated using Fourier transform infrared spectroscopy performed on all pure samples and prepared mixtures at room temperature (23 ± 2 °C), as well as a complete thermal stress evaluation (TG—thermogravimetric/DTG—derivative thermogravimetric/DSC—differential scanning calorimetry). The results showed particularities for all analyzed mixtures, α-lactose monohydrate, starch, sorbitol, magnesium stearate, calcium lactate and magnesium citrate proving to be safe to use together with mirtazapine in binary mixtures at temperatures below 130 °C, while for polyvinylpyrrolidone K30 and aerosol precautions need to be considered at temperatures over 100 °C. The association of mirtazapine with D-mannitol or stearic acid proved to raise concerns even at room temperature, indicating possible interactions that may alter the chemical integrity of the active pharmaceutical ingredient and with it, its therapeutic effect. These findings should be taken into consideration during the selection of the technological procedures used in the manufacturing process of dosage forms that include mirtazapine alongside with any of these excipients so that unwanted chemical interactions could be avoided.