Cichoric acid aerosol for inhalation therapy in respiratory syncytial virus

Abstract

Cichoric acid (CA) is a caffeic acid derivative, which has significant anti respiratory syncytial virus (RSV) effect and low toxicity. However, due to the low oral bioavailability and poor intestinal absorption of CA, it is not suitable to be made into oral preparations. In this study, CA was made into metered dose inhaler (MDI), allowing the drug to target the site of action, thus achieving more effective treatment. Through preliminary experiments, the drug content and prescription composition of the preparation were determined. Clarity and stability of solution were used as indexes to screen the composition of latent solvent. Single factor and orthogonal test were used to optimize the amount of latent solvent in CA-MDI, and the optimal prescription was verified. The aerosol prepared according to the optimal formula was characterized and preliminary stability was studied. The final formula of CA-MDI was: CA 15 mg, absolute ethanol 1 g, propylene glycol 0.4 g and 1,1,1,2-tetrafluoroethane 10 g. CA-MDI was prepared with the best prescription, with the specification of 150 actuation per bottle and 75 μg per actuation. After quality inspection, three batches of inhaled aerosols showed that the main drug content per bottle was 77.91 ± 1.63 μg (n = 3), and the total number of bottles was 185 ± 3 (n = 3), all of which met the standards of China Pharmacopoeia and the proposed specifications. The preliminary stability study showed that the quality of inhaled aerosols in CA was stable and reliable.