Mometasone Furoate (19-18-7) Physical and Chemical Properties
Mometasone Furoate
A high‑potency synthetic corticosteroid ester used as an active pharmaceutical ingredient for topical, nasal and inhalation products; relevant to formulation development, QC and analytical reference work.
| CAS Number | 19-18-7 |
| Family | Steroid ester (corticosteroid) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP, JP, USP |
Mometasone furoate is a synthetic corticosteroid of the steroid‑ester structural class (a 2‑furoate ester of a pregna‑1,4‑diene‑3,20‑dione core). The structure contains a tetracyclic steroid nucleus bearing a 17‑position furoate ester, a secondary 11β‑hydroxyl, two chlorine substituents and multiple ketone and methyl functionalities. Electronically, the molecule combines a largely nonpolar steroid scaffold with localized polar functionality (one H‑bond donor, multiple carbonyl and ether acceptors), giving amphipathic character concentrated around the ester and hydroxy/keto regions.
Physicochemically, mometasone furoate behaves as a neutral, lipophilic small molecule with limited aqueous solubility and a propensity to partition into lipid phases and biological membranes. The furoate ester increases lipophilicity and susceptibility to esterase‑mediated hydrolysis relative to the free acid/alcohol; the dichloro substituents further elevate hydrophobicity. Under typical formulation and physiological conditions the compound is essentially nonionized (no ionizable basic or acidic groups with pKa in the physiological range), and is metabolized hepatically (notably by cytochrome P450 3A4) rather than undergoing simple acid–base conversion.
Pharmaceutically, mometasone furoate is used as a topical and inhaled glucocorticoid receptor agonist with high receptor affinity and low systemic bioavailability in recommended routes; formulations include dry powder inhalers, nasal suspensions and topical ointments. Common commercial grades reported for this substance include: BP, EP, JP, USP.
Basic Physicochemical Properties
Molecular and computed descriptors indicate a relatively large, complex steroid ester with both polar and lipophilic domains. Key computed properties reported are: - Molecular formula: \(\ce{C27H30Cl2O6}\) - Molecular weight: 521.4 - Exact / monoisotopic mass: 520.1419441 - XLogP / computed lipophilicity: 3.9 (XLogP3); reported LogP: 4.115 - Topological polar surface area (TPSA): 93.8 - Hydrogen bond donors: 1 - Hydrogen bond acceptors: 6 - Rotatable bond count: 5 - Defined atom stereocenter count: 8 - Complexity: 1020
These parameters are consistent with a moderately lipophilic, low‑solubility corticosteroid that will preferentially partition to lipid matrices and biological membranes while retaining a polar surface sufficient for receptor interaction.
Density and Solid-State Form
No experimentally established value for this property is available in the current data context.
Crystallographic information is available (single‑crystal and deposited crystallographic descriptors are reported), indicating that the substance can form well‑defined crystalline solids suitable for analytical characterization. Synonym entries and reference standards indicate existence of both anhydrous and monohydrate designations in material listings; solid‑state form (polymorph, hydrate status) should be confirmed for any production or analytical specification batch.
Melting Point
An experimental melting point range is reported as \(\,215\text{–}228\,^\circ\mathrm{C}\). This high melting range is typical for rigid, polycyclic steroid frameworks with extensive intermolecular contacts in the crystalline lattice.
Solubility and Dissolution Behavior
Solubility: Insoluble (reported).
The combination of a steroid core, ester linkage and dichloro substituents yields substantial lipophilicity (reported LogP \(\approx 4.115\)), which explains the practical insolubility in water. For formulation, low aqueous solubility requires use of techniques such as micronization (for dry powder inhalers), suspensions (nasal sprays), solubilizing excipients or nonaqueous vehicles (topical ointments). Ester hydrolysis may occur in vivo or under strongly acidic/basic conditions; hence dissolution and release profiles can be influenced by local esterase activity and formulation pH.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
Qualitatively, mometasone furoate is effectively neutral across the usual environmental and physiological pH range. It lacks ionizable groups with pKa values in the aqueous/physiological window; the single hydroxyl is secondary and not readily deprotonated under normal conditions. Therefore aqueous ionization does not drive solubility or membrane permeation; partitioning is dominated by lipophilicity.
Reactivity and Stability
The molecule is a steroidal furoate ester and shows the generic reactivity profile of such compounds: the ester linkage is susceptible to hydrolytic cleavage (chemical hydrolysis under strong acidic or basic conditions and enzymatic hydrolysis by esterases in biological systems). Ketone and hydroxy functionalities are potential sites for reduction/oxidation under aggressive conditions. Photochemical or oxidative degradation is possible for sensitive chromophores (the furan ring and conjugated enone system), so light and oxidant exposure should be minimized during storage and processing.
Metabolism is primarily hepatic via cytochrome P450 3A4, producing metabolites including free mometasone and hydroxylated products. High plasma protein binding (reported 98–99% in vitro at relevant concentrations) reduces free systemic concentrations but also impacts elimination and potential drug–drug interactions mediated by metabolic pathways.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: \(\ce{C27H30Cl2O6}\)
- Molecular weight: 521.4
- Exact mass: 520.1419441
- Monoisotopic mass: 520.1419441
LogP and Structural Features
Reported lipophilicity values: - XLogP3: 3.9 - Reported LogP: 4.115
Structural contributors to lipophilicity include the tetracyclic steroid nucleus and two chlorine substituents; the furoate ester further increases hydrophobicity relative to the corresponding alcohol. Polar contributions arise from the 11β‑hydroxyl, multiple carbonyls and the furan oxygen, producing a TPSA of 93.8 that supports receptor binding but not high aqueous solubility. The single hydrogen bond donor and six acceptors reflect localized polarity rather than overall ionic character.
Structural Identifiers (SMILES, InChI)
- SMILES:
C[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)CCl)OC(=O)C5=CC=CO5)C)O)Cl)C - InChI:
InChI=1S/C27H30Cl2O6/c1-15-11-19-18-7-6-16-12-17(30)8-9-24(16,2)26(18,29)21(31)13-25(19,3)27(15,22(32)14-28)35-23(33)20-5-4-10-34-20/h4-5,8-10,12,15,18-19,21,31H,6-7,11,13-14H2,1-3H3/t15-,18+,19+,21+,24+,25+,26+,27+/m1/s1 - InChIKey:
WOFMFGQZHJDGCX-ZULDAHANSA-N
(Identifiers shown exactly as reported; SMILES and InChI provided as inline code.)
Identifiers and Synonyms
Registry Numbers and Codes
- CAS RN: 19-18-7
- European Community (EC) Number: 617-501-0
- UNII: 04201GDN4R
- ChEBI ID: CHEBI:47564
- ChEMBL ID: CHEMBL1161
- DrugBank ID: DB14512
- DSSTox Substance ID: DTXSID4023333
- KEGG ID(s): C07817, D00690
- NSC Number: 746171
- InChIKey: WOFMFGQZHJDGCX-ZULDAHANSA-N
(Only registry codes and identifiers reported in the technical context are listed.)
Synonyms and Brand-Independent Names
Common synonyms and nonproprietary names encountered in material and analytical listings include: mometasone furoate; mometasone 17‑furoate; MOMETASONE FUROATE; (11β,16α)-9,21‑dichloro‑11‑hydroxy‑16‑methyl‑3,20‑dioxopregna‑1,4‑dien‑17‑yl furan‑2‑carboxylate. Depositor and reference synonyms include Asmanex, Elocon, Nasonex and multiple formulation/standard designations and registry aliases. When preparing specifications or purchasing material, consult the supplier’s naming and reference standard nomenclature to ensure the intended substance and form are procured.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Mometasone furoate is used primarily as an active pharmaceutical ingredient (API) in topical, intranasal and inhaled corticosteroid preparations. It functions as a glucocorticoid receptor agonist with high receptor affinity, delivering anti‑inflammatory, anti‑pruritic and vasoconstrictive effects at local sites of application while minimizing systemic exposure in recommended dosing forms. It is also present as the active moiety in combination therapies for upper respiratory allergic conditions.
Formulation and Development Contexts
Typical formulation contexts include: - Dry powder inhaler formulations (micronized API in carrier blends or device metering systems). - Aqueous or suspension nasal sprays (suspension stability, particle size distribution and wetting behavior are formulation challenges given low aqueous solubility). - Topical ointments/creams where nonaqueous vehicles and penetration enhancers control local bioavailability.
Key development considerations are control of particle size and morphology for inhalation/nasal delivery, stabilization of the crystalline form to avoid polymorphic conversion, mitigation of ester hydrolysis during manufacturing and appropriate selection of excipients to ensure content uniformity and dose delivery. No concise application summary beyond these general roles is provided in the current data context; in practice the substance is selected based on its general properties described above.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Material for pharmaceutical use is typically supplied as a pharmaceutical reference standard or API meeting pharmacopoeial criteria. Analytical and reference standards are commonly supplied for assay, impurity profiling and method development. Typical grade concepts include: - Pharmaceutical (API) grade — for use in finished medicinal products subject to regulatory manufacturing controls. - Analytical/Reference standard — for HPLC/assay calibration and identity confirmation. - Technical/industrial grade — for non‑clinical research or manufacturing development.
Reported commercial grade designations for mometasone furoate include: BP, EP, JP, USP.
General Quality Attributes (Qualitative Description)
Quality attributes of importance include: - Identity (structure, stereochemistry and InChIKey confirmation). - Assay (potency by validated chromatographic methods). - Purity (control of related steroidal impurities and residual solvents). - Solid‑state form (polymorph/hydrate status and particle size distribution). - Stability (shelf stability under protected conditions, sensitivity to hydrolysis and oxidation).
Specific limits, assay percentages or impurity thresholds are set in pharmacopoeial monographs and supplier specifications and are not reproduced here.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
- GHS hazard information aggregated from notifications indicates potent hazard endpoints including reproductive toxicity (noted as H360 / Repr. 1B in a majority of notifications) and organ toxicity (STOT‑SE/STOT‑RE classifications reported in subsets). Aquatic chronic toxicity is also reported for a fraction of notifications.
- In vitro protein binding is high (reported 98–99%), which affects free systemic concentrations and elimination kinetics.
- Metabolism is primarily hepatic (CYP3A4), with potential for metabolic interactions with inhibitors/inducers of that enzyme pathway.
- Clinical and formulation use as inhaled or topical preparations is designed to minimize systemic exposure; nonetheless, occupational handling of the bulk API requires controls to prevent inhalation and dermal exposure.
Appropriate precautions during handling include minimizing dust formation, using local exhaust ventilation or containment for powder operations, and wearing suitable personal protective equipment (gloves, eye protection and respiratory protection where dust/aerosol exposure may occur). For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
Storage and Handling Guidelines
- Store in a cool, dry, well‑sealed container protected from light and oxidizing agents to limit hydrolysis and oxidative degradation.
- Avoid conditions that promote moisture uptake if an anhydrous form is specified; conversely, confirm hydrate status if material is supplied as a monohydrate.
- Use good manufacturing practice (GMP) and containment for weighing and transfer of API quantities; control electrostatic discharge and dust explosion risk as applicable for fine powders.
- For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
