Alclometasone Dipropionate (66734-13-2) Physical and Chemical Properties
Alclometasone Dipropionate
Synthetic corticosteroid dipropionate API used in topical dermatological formulations, relevant to formulation development, procurement and quality control.
| CAS Number | 66734-13-2 |
| Family | Corticosteroid (glucocorticoid) |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP, USP |
Alclometasone dipropionate is a synthetic corticosteroid ester of the prednisolone series; structurally it is a 17,21-dipropionate derivative of a 7‑chloro, 16‑methyl prednisolone scaffold. The molecule is a polycyclic steroidal framework (cyclopenta[a]phenanthrene core) bearing a 3‑oxo and a 20‑oxo functionality, an 11β‑hydroxy substituent and two esterified hydroxyls (propionate esters) at the 17‑ and 21‑positions. A single chlorine atom at the 7‑position and multiple defined stereocenters (nine specified centers) give a rigid, stereodefined, relatively bulky neutral molecule with limited conformational flexibility in the core and several flexible ester-linked side chains.
Electronically, the compound is neutral (formal charge 0) and contains polar functionality (carbonyls, an alcohol, multiple ester oxygens) combined with an extended hydrophobic steroid nucleus. This gives a balanced profile of lipophilicity and polar surface area: sufficient lipophilicity to partition into lipid-rich tissues and topical dosage vehicles, while the polar groups support limited aqueous interactions and permit enzymatic metabolism (ester hydrolysis). As a corticosteroid ester, it is not ionizable in the physiological pH range and is typically formulated for topical or ophthalmic administration where local glucocorticoid receptor agonism yields anti‑inflammatory, antipruritic and vasoconstrictive effects.
Common commercial grades reported for this substance include: EP, USP.
Basic Physicochemical Properties
Density and Solid-State Form
No experimentally established value for this property is available in the current data context.
Melting Point
No experimentally established value for this property is available in the current data context.
Solubility and Dissolution Behavior
Alclometasone dipropionate is a steroid dipropionate ester and therefore exhibits low aqueous solubility and appreciable solubility in nonpolar organic solvents, oils and lipophilic excipients commonly used in topical and ophthalmic vehicles. The propionate ester groups increase lipophilicity relative to the parent alcohol, favoring partitioning into stratum corneum lipids and membrane phases. In biological systems the ester linkages are susceptible to enzymatic hydrolysis (esterase‑mediated), which converts the dipropionate into the more polar parent corticosteroid and thereby changes solubility and local bioavailability. Formulation approaches for topical use therefore emphasize emulsions, ointments, microemulsions or solvent systems that maximize the drug residence time in target tissues while controlling release and minimizing systemic absorption.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
Reactivity and Stability
The primary chemical liabilities are ester hydrolysis and oxidative or photochemical degradation of the steroid nucleus. The two propionate esters at C‑17 and C‑21 are susceptible to hydrolysis under acidic, basic or enzymatic conditions; hydrolysis yields the corresponding alcoholic corticosteroid which has different physicochemical and pharmacokinetic properties. The 11β‑hydroxy and 3‑oxo functionalities can participate in oxidation or keto–enol tautomeric-like behavior under aggressive conditions, and the 7‑chloro substituent renders the local ring system somewhat more resistant to metabolic dechlorination but may influence oxidative pathways. For storage and handling, protection from moisture, strong acids or bases, and prolonged exposure to light and heat reduces the risk of hydrolytic or oxidative degradation. Compatibility with formulation excipients should be evaluated empirically because reactive impurities or strong nucleophiles can accelerate ester cleavage.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: \(\ce{C28H37ClO7}\)
- Molecular weight (reported): 521.0
- Exact / monoisotopic mass: 520.2227812
The formula \(\ce{C28H37ClO7}\) indicates one chlorine atom and multiple oxygen-containing functional groups (one secondary alcohol, several carbonyls and ester oxygens), consistent with moderate polar surface area and a largely hydrocarbon steroid core.
LogP and Structural Features
- Reported XLogP3: 3.2
- Topological polar surface area (TPSA): 107
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 7
- Rotatable bond count: 8
An XLogP3 of 3.2 together with TPSA 107 reflects a molecule with appreciable lipophilicity but sufficient polar surface to support limited aqueous interactions. The single hydrogen bond donor (11β‑OH) and multiple acceptors (carbonyls and ester oxygens) are consistent with reversible interactions with protein binding sites and ester‑hydrolyzing enzymes. Rotatable bonds are predominantly in the side chains (ester linkers), while the steroid core is conformationally rigid.
Structural Identifiers (SMILES, InChI)
- SMILES:
CCC(=O)OCC(=O)[C@]1([C@@H](C[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2[C@@H](CC4=CC(=O)C=C[C@]34C)Cl)O)C)C)OC(=O)CC - InChI:
InChI=1S/C28H37ClO7/c1-6-22(33)35-14-21(32)28(36-23(34)7-2)15(3)10-18-24-19(29)12-16-11-17(30)8-9-26(16,4)25(24)20(31)13-27(18,28)5/h8-9,11,15,18-20,24-25,31H,6-7,10,12-14H2,1-5H3/t15-,18+,19-,20+,24-,25+,26+,27+,28+/m1/s1 - InChIKey:
DJHCCTTVDRAMEH-DUUJBDRPSA-N
(Identifiers above are provided as structural descriptors for unambiguous chemical identification.)
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 66734-13-2
- EC number: 266-464-3
- UNII: S56PQL4N1V
- ChEBI: CHEBI:31184
- ChEMBL: CHEMBL1200989
- RXCUI: 17268
- InChIKey: DJHCCTTVDRAMEH-DUUJBDRPSA-N
Synonyms and Brand-Independent Names
Reported synonyms and alternative names include: alclometasone dipropionate; 7‑alpha‑chloro‑16‑alpha‑methylprednisolone 17,21‑dipropionate; Alclometasone 17,21‑dipropionate; Aclovate; Delonal; Vaderm; Sch 22219; Almeta; Modrasone; and related systematic IUPAC descriptors. These synonyms reflect both chemical nomenclature and commonly used nonproprietary or product names.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Alclometasone dipropionate is used as a topical glucocorticoid active ingredient for the relief of inflammatory and pruritic manifestations of corticosteroid‑responsive dermatoses and has been employed in ophthalmic preparations for inflammatory eye conditions. It acts as a glucocorticoid receptor agonist that modifies gene transcription to exert anti‑inflammatory, immunosuppressive and vasoconstrictive effects. The dipropionate ester form is chosen to modulate lipophilicity, skin penetration and local potency relative to the parent alcohol.
Formulation and Development Contexts
In formulation development, the dipropionate ester is selected for incorporation into creams, ointments, lotions and ophthalmic vehicles where controlled skin penetration and localized activity are required. Formulators must balance drug partitioning into lipid phases with the potential for local ester hydrolysis; selection of emollients, solvents and penetration enhancers affects both efficacy and systemic exposure risk. Analytical methods for stability and assay typically monitor ester integrity and presence of hydrolysis products.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical commercial and specification grades for active pharmaceutical ingredients are represented by pharmacopoeial and analytical grades. For this substance the following commercial grades are reported: EP, USP. These indicate availability of material in pharmacopeial quality intended for pharmaceutical manufacturing and analytical reference.
General Quality Attributes (Qualitative Description)
Pharmaceutical grade material is expected to conform to standards for identity, assay, related substances (impurities and degradation products), residual solvents and microbial limits appropriate to topical APIs. Key quality attributes include assay of the dipropionate form, limits on free alcohol (hydrolysis impurity), control of related steroidal impurities and stereochemical purity (configured centers). Suppliers typically provide certificates of analysis documenting these qualitative attributes.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Alclometasone dipropionate is a glucocorticoid with topical pharmacology; systemic toxicity risk increases with excessive, prolonged or occluded application. Reported hazard classifications include concern for reproductive toxicity and target‑organ effects upon prolonged exposure. Documented hazard statements in reported classifications include: H312 (harmful in contact with skin), H315 (causes skin irritation), H319 (causes serious eye irritation), H360 (may damage fertility or the unborn child), H361 (suspected of damaging fertility or the unborn child), and H373 (may cause damage to organs through prolonged or repeated exposure). These reported hazard codes indicate the need for precautions to prevent dermal or ocular exposure and to limit repeated systemic absorption. For therapeutic topical use, product labeling and clinical dosing recommendations mitigate systemic risk; industrial handling should assume potential reproductive and organ toxicity hazards.
Storage and Handling Guidelines
Store in a cool, dry, well‑sealed container protected from light and moisture; avoid exposure to strong acids or bases that can promote hydrolysis. Use appropriate engineering controls to minimize dust generation if working with solid material. Personnel should use gloves, eye protection and protective clothing to prevent skin and eye contact; respiratory protection may be warranted if airborne dust or aerosol can be generated. In case of accidental exposure, remove contaminated clothing and wash skin thoroughly; for eye exposures, flush with water and seek medical attention. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
