Miconazole (R18134) is an imidazole antifungal compound/agent. Miconazole also has antibacterial properties.

Physicochemical Properties

Molecular Formula	C18H14CL4N2O
Molecular Weight	416.13
Exact Mass	413.986
CAS #	22916-47-8
Related CAS #	Miconazole nitrate;22832-87-7;Miconazole-d5;1216653-50-7;Miconazole-d5 nitrate;1216653-51-8;Miconazole-d2;2140316-33-0
PubChem CID	4189
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	555.1±50.0 °C at 760 mmHg
Melting Point	159-163ºC
Flash Point	289.5±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.625
LogP	5.93
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	417
Defined Atom Stereocenter Count	0
InChi Key	BYBLEWFAAKGYCD-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H14Cl4N2O/c19-13-2-1-12(16(21)7-13)10-25-18(9-24-6-5-23-11-24)15-4-3-14(20)8-17(15)22/h1-8,11,18H,9-10H2
Chemical Name	1-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]imidazole
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Miconazole is a topical imidazole antifungal medication that was created by Janssen Pharmaceutica to treat fungal infections of the skin or mucous membranes. Ergosterol is a crucial component of fungal cell membranes, and it functions by preventing its formation. Additionally, it is utilized to combat some species of Leishmania, a single-celled parasite whose cell membrane also contains ergosterol. It also possesses certain antibacterial qualities in addition to its antifungal and antiparasitic actions. Miconazole is also utilized as a formaldehyde substitute in the development of Ektachrome film during the Kodak E-6 process' final processing, as well as in the comparable Fuji CR-56 process. In the composition of its C-41RA Quick Access color negative developing process, Fuji Hunt also incorporates Miconazole as a final rinse ingredient.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Miconazole given to healthy volunteers as a single 50 mg oral tablet produced a mean Cmax of 15.1 ± 16.2 mcg/mL, a mean AUC0-24 of 55.2 ± 35.1 mcg\*h/mL, and a median Tmax of 7 hours (range 2.0-24.1). In these patients measurable plasma concentrations ranged from 0.5 to 0.83 mcg/mL. Topical miconazole is absorbed poorly into the systemic circulation. In pediatric patients aged 1-21 months given multiple topical applications of miconazole ointment for seven days, the plasma miconazole concentration was less than 0.5 ng/mL in 88% of the patients, with the remaining patients having a concentration of 0.57 and 0.58 ng/mL, respectively. Similarly, patients. administered with a vaginal 1200 mg ovule had a mean Cmax of 10.71 ng/mL, mean Tmax of 18.4 hours, and mean AUC0-96 of 477.3 ng\*h/mL. Miconazole is excreted through both urine and feces; less than 1% of unchanged miconazole is recovered in urine. A 1200 mg miconazole vaginal suppository resulted in a calculated apparent volume of distribution of 95 546 L while a 100 mg vaginal cream yielded an apparent volume of distribution of 10 911L. Metabolism / Metabolites Miconazole is metabolized in the liver and does not give rise to any active metabolites. Biological Half-Life Miconazole has a terminal half-life of 24 hours.
Toxicity/Toxicokinetics	Toxicity Summary Miconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Miconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis. Toxicity Data LD50: 3800 mg/kg (Oral, Mouse) (A308) LD50: 3 gm/kg (Oral, Rat) (A308)
References	[1]. http://en.wikipedia.org/wiki/Miconazole. [2]. New insights on the antibacterial efficacy of miconazole in vitro. Mycoses. 2017 Aug;60(8):552-557.
Additional Infomation	Pharmacodynamics Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (240.31 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.01 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 25.0 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. Solubility in Formulation 2: 2.08 mg/mL (5.00 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.00 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4031 mL	12.0155 mL	24.0310 mL
	5 mM	0.4806 mL	2.4031 mL	4.8062 mL
	10 mM	0.2403 mL	1.2015 mL	2.4031 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.