Lung fibroblasts that have been isolated from the lung are prevented from activating by flunisolide (0.1–10 μM, 1 hour) [1]. Flunisolide (10 μM, 24 hours) causes sputum eosinophils to undergo apoptosis and decreases the release of MMP-9, TIMP-1, TGF-β, and fibronectin from sputum cells isolated from individuals with mild to moderate asthma [2]. In BEAS-2B cells, flunisolide (0.1–10 µM µM, 24 hours) efficiently suppresses TNF-α-induced ICAM-1 expression as well as GM-CSF and IL-5 production [3]. It has been demonstrated that flunisolide (115 µM, 0–3 hours) is ATP-dependent and can move polarizedly in Calu-3 cells from the apical (ap) to the basolateral (bl) direction [4].

In silicosis mice, flunisolide (intranasal treatment, 0.3–10 µg/mouse, daily, commencing on days 21–27) enhances the rate of silicon particle clearance in the lungs while simultaneously inhibiting lung inflammation, fibrosis, and airway hyperresponsiveness [1]. The intranasal administration of flunisolide (0.3–10 µg/mouse, daily, days 21–27) prevents the formation of macrophages and myofibroblasts in lung tissue caused by silica [1].

Apoptosis analysis [2]
Cell Types: eosinophils
Tested Concentrations: 10 μM
Incubation Duration: 24 h
Experimental Results: Induced apoptosis of sputum eosinophils.

Animal/Disease Models: Male Swiss-Wechsler mouse (intranasal instillation, crystalline silica, 10 mg/50 µL, particle size 0.5-10 µm) [1]
Doses: 0.3-10 µg/mouse daily, day 21 -27-day intranasal administration
Experimental Results: diminished granulomatous reactions, collagen deposition associated with granuloma formation induced by silica particles. Reduce the number of F4/80 and α-SMA positive cells.

Absorption, Distribution and Excretion
Absorption is rapid. Metabolism/Metabolites Primarily metabolized in the liver, converted into Sβ-OH metabolites. Biological Half-Life 1.8 hours

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Although measurements have not been performed, the amount of inhaled corticosteroids absorbed into the mother's bloodstream and secreted into breast milk is likely too small to affect breastfed infants. Expert opinion is that inhaled, nasal, and oral corticosteroids are safe to use during lactation.
◉ Effects on Breastfed Infants
Currently, there are no reports of any effects of corticosteroids on breastfed infants.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding Rate
Approximately 40% after oral inhalation.

[1]. Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice. Front Endocrinol (Lausanne). 2020 Jun 17;11:388.

[2]. In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics. Allergy. 2004 Sep;59(9):927-32.

[3]. Modulation by flunisolide of tumor necrosis factor-alpha-induced stimulation of airway epithelial cell activities related to eosinophil inflammation. J Asthma. 2010 May;47(4):381-7.

[4]. Evidence of P-glycoprotein mediated apical to basolateral transport of flunisolide in human broncho-tracheal epithelial cells (Calu-3). Br J Pharmacol. 2001 Dec;134(7):1555-63.

According to state or federal labeling requirements, flunisolone may cause developmental toxicity and female reproductive toxicity. Flunisolone is a fluorinated steroid, cyclic ketal, 20-oxosteroid, 21-hydroxysteroid, 11β-hydroxysteroid, 3-oxo-Δ(1),Δ(4)steroid, and primary α-hydroxyketone. It has immunosuppressant, anti-inflammatory, and anti-asthmatic effects. Flunisolone (trade names: AeroBid, Nasalide, Nasarel) is a corticosteroid with anti-inflammatory effects. It is commonly used to treat allergic rhinitis, and its main mechanism of action is activation of glucocorticoid receptors. Anhydrous flunisolone is a corticosteroid. The mechanism of action of anhydrous flunisolone is as a corticosteroid hormone receptor agonist. Flunisolone is a synthetic corticosteroid with anti-inflammatory and anti-allergic properties. Flunisolone is a glucocorticoid receptor agonist that binds to cytoplasmic glucocorticoid receptors, then translocates to the nucleus, initiating the transcription of glucocorticoid-responsive genes (such as lipocortin). Lipocorticoids inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and inhibiting the synthesis of prostaglandins and leukotrienes, both potent inflammatory mediators. Drug Indications For maintenance and prophylactic treatment of asthma. FDA Label Mechanism of Action Flunisolone is a glucocorticoid receptor agonist. The anti-inflammatory effects of corticosteroids are thought to be related to lipocortin, a phospholipase A2 inhibitory protein that controls the biosynthesis of prostaglandins and leukotrienes by inhibiting arachidonic acid. Corticosteroids suppress the immune system by reducing lymphatic function, decreasing immunoglobulin and complement concentrations, inducing lymphopenia, and interfering with antigen-antibody binding. Flunisolone binds to the plasma cortisol transporter and is active only when it is no longer bound to the cortisol transporter.

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Pharmacodynamics
Flunisolone is a synthetic corticosteroid. It is used in the form of a metered-dose inhaler to treat asthma, or in the form of a nasal spray to treat allergic rhinitis. Corticosteroids are naturally occurring hormones that can prevent or suppress inflammatory and immune responses. When used as a nasal spray, flunisolone can reduce common allergy symptoms such as runny nose, nasal congestion, postnasal drip, sneezing, and itching at the back of the throat.

C24H31FO6

434.4977

434.21

3385-03-3

Flunisolide hemihydrate;77326-96-6;Flunisolide-d6

82153

White to off-white solid powder

1.33g/cm3

581.8ºC at 760mmHg

237-240°C (dec.)

305.7ºC

2.274

2

7

2

31

910

9

C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1C[C@@H]4[C@]2(OC(O4)(C)C)C(=O)CO)C[C@@H](C5=CC(=O)C=C[C@]35C)F)O

XSFJVAJPIHIPKU-XWCQMRHXSA-N

InChI=1S/C24H31FO6/c1-21(2)30-19-9-14-13-8-16(25)15-7-12(27)5-6-22(15,3)20(13)17(28)10-23(14,4)24(19,31-21)18(29)11-26/h5-7,13-14,16-17,19-20,26,28H,8-11H2,1-4H3/t13-,14-,16-,17-,19+,20+,22-,23-,24+/m0/s1

(1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

NasarelFlunisolideBronalideLunisAeroBidNasalideSynaclyn

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~287.69 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)