Assessing the Safety of Carbon Dioxide Extracts of Acorus calamus Rhizomes and Calendula officinalis Flowers and the Antitussive Activity of the Tablet Dosage Form 'Exkair' and Granules 'Zerp-Ak-Broncho' Developed on Their Basis.

Background: The growing demand for safe and effective phytopharmaceuticals underscores the importance of studying regionally available medicinal plants. Acorus calamus L. and Calendula officinalis L., widely distributed in the Republic of Kazakhstan, are promising sources of biologically active compounds with significant pharmacological potential. However, the combined use of their CO2 extracts remains insufficiently characterised, particularly regarding possible synergistic interactions. Therefore, the development of new dosage forms and their comprehensive pharmacological and toxicological evaluation is a priority in modern pharmaceutical research. Methods: Concentrated extracts from Acorus calamus rhizomes and Calendula officinalis flowers were obtained using precritical CO2 extraction. Safety was assessed through acute and chronic toxicity studies in laboratory animals according to standard non-clinical guidelines. Animals received graded doses of the extracts and developed formulations ('Exkair' tablets and 'Zerp-Ak-Broncho' granules). Clinical condition, mortality, body weight, and behaviour were monitored. Biochemical, haematological, and histopathological analyses were performed. Antitussive activity was evaluated in vivo by measuring oedema inhibition relative to reference drugs. Results: The CO2 extracts and formulations demonstrated low toxicity and good tolerability, with no mortality or significant adverse effects observed even at high doses. Biochemical and haematological parameters remained within physiological ranges, and histopathological examination revealed no structural alterations in internal organs. Both 'Exkair' and 'Zerp-Ak-Broncho' exhibited pronounced antitussive activity, confirmed by significant suppression of oedema. This effect is likely associated with the synergistic action of flavonoids, terpenoids, and phenolic compounds. Conclusions: The findings indicate that CO2 extracts of Acorus calamus L. and Calendula officinalis L., as well as the developed formulations, possess a favourable safety profile and significant antitussive activity. These results support their further development as phytotherapeutic agents in Kazakhstan.