Complexation of Andrographolide, Mirabegron and Suvorexant and Bioactivity Study of the Complexes

Abstract

Background: There are many ways to synthesize new drug molecules for more potent therapeutic efficacy with minimum side effects. The drugs may exhibit therapeutic effects independently or may interfere with each other. Method: In this study, new drug molecules were synthesized by drug-drug complexation way according to the calculated w/w ratio. The complexes were prepared by solid-mixing method using pestle and mortar by adding equal amount of drugs to each other, then warmed at 50 °C for 4 hours and left at room temperature for overnight to obtain new drug complexes. The new drug complexes were distinguished by Differential Scanning Calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) with the biological activity. Results: The melting endothermic peaks of andrographolide-suvorexant, andrographolidemirabegron, and suvorexant-mirabegron complexes were found at 221.02 °C, 189.49 °C and 115.78 °C, respectively which were different from the melting endotherms of andrographolide, suvorexant and mirabegron at 230.87 °C, 127.09 °C and 140.40 °C, respectively. The FTIR spectra of the formed complexes showed the similar characteristics of the standard drugs. The cytotoxic effect of the drug complexes on HeLa cell line were higher (10% less survived HeLa cell, i.e. > 90 % cell died) than the precursor drug molecules. Conclusion: Our research findings that three new drug compounds were synthesized by complexation way which could be due to interaction of andrographolide and suvorexant; andrographolide and mirabegron, and suvorexant and mirabegron.

Optimization of Production Parameters for Andrographolide-Loaded Nanoemulsion Preparation by Microfluidization and Evaluations of Its Bioactivities in Skin Cancer Cells and UVB Radiation-Exposed Skin

“…The characteristic bands shown in the FT-IR spectrum of AG at a wavenumber of 1366 cm −1 represented vibration of –CH 3 . The bands at wavenumber 1672 cm −1 and 1724 cm −1 responded to stretching vibrations of C=O and the band at a wavenumber of 3385 cm −1 was assigned for stretching the vibration of hydrogen bonded in –O-H in the molecule of AG [ 27 ]. The band in the FT-IR spectrum of Blank NE at a wavenumber 1452 cm −1 responded to a bending vibration of C-H in the chemical structure of some ingredients in Blank NE, such as coconut oil [ 28 ].…”

Improved Pharmacokinetic Feasibilities of Mirabegron-1,2-Ethanedisulfonic Acid, Mirabegron-1,5-Naphthalenedisulfonic Acid, and Mirabegron-L-Pyroglutamic Acid as Co-Amorphous Dispersions in Rats and Mice

“…Since the used doses in this study (30 mg/kg in rats and 50 mg/kg in mice) were lower than the doses causing even slight side effects (250 mg/kg in rats and 100 mg/kg in mice [ 46 ]), the used doses in this study are appropriate within safe dose ranges. In addition, a 2.5 mg/mL of MBR showed <82% of cytotoxicity in in vitro HeLa cells [ 47 ]. The plasma concentrations of MBR, especially C max values of 0.491–1.09 µg/mL in rats and 0.0672–0.261 µg/mL in mice, were lower than 2.5 mg/mL showing in vitro cytotoxicity.…”