Dextromethorphan hydrobromide monohydrate (19-10-9) Physical and Chemical Properties
Dextromethorphan hydrobromide monohydrate
Hydrobromide monohydrate salt of dextromethorphan supplied as a crystalline pharmaceutical form for formulation, analytical reference, and R&D use.
| CAS Number | 19-10-9 |
| Family | Morphinan derivatives |
| Typical Form | Crystalline hydrobromide monohydrate (powder) |
| Common Grades | EP, JP, USP |
Dextromethorphan hydrobromide monohydrate is the hydrobromide salt and monohydrate form of dextromethorphan, a morphinan-class tertiary amine. Structurally it comprises the morphinan tricyclic core bearing a 3-methoxy substituent and a N-methyl tertiary amine; in the hydrobromide monohydrate the amine exists as the protonated cation paired with bromide and a molecule of crystallization water. The solid is therefore a salt hydrate rather than a neutral free base, and this fundamentally governs its solid-state packing, hygroscopicity and aqueous behaviour.
Electronically the molecule features a single basic center (tertiary amine) and a single ether oxygen on the aromatic ring; the topological polar surface area (TPSA) is low (13.5), indicating limited polar surface for passive polar interactions in the free base. As the hydrobromide salt the compound is protonated and thus displays substantially increased aqueous ionicity and apparent polarity compared with the neutral base. Class-level behaviour: the protonated morphinan salt is significantly more water‑soluble than the free base, is stable to routine handling, and is compatible with common formulation excipients used in oral liquids and tablets; the free base is more lipophilic and membrane-permeable.
Pharmacotechnical relevance: this salt hydrate is the pharmaceutical active form used in antitussive preparations and in formulation development where enhanced aqueous solubility and controlled hygroscopicity are required. Common commercial grades reported for this substance include: EP, JP, USP.
Basic Physicochemical Properties
Density and Solid-State Form
No exact bulk or crystalline density value for this property is available in the current data context. The substance is reported as a hydrobromide salt and monohydrate (salt·H2O); it is therefore a crystalline salt hydrate containing one stoichiometric water of crystallization. Analytical identity data reported include ATR‑IR and FT‑Raman spectra obtained from neat samples, consistent with a defined crystalline salt form. The presence of a hydrate implies potential loss of water on heating and sensitivity of measured solid‑state properties to drying history.
Melting Point
No experimentally established value for this property is available in the current data context.
Solubility and Dissolution Behavior
Reported solubility: >55.5 [ug/mL] (The mean of the results at pH 7.4). The hydrobromide salt form substantially increases water solubility relative to the neutral free base because the tertiary amine is protonated and exists as a water‑soluble cation. Dissolution behaviour for this class of salts is typically pH‑dependent only insofar as deprotonation (liberation of the free base) will reduce aqueous solubility; under near‑physiological conditions (e.g., \(\mathrm{pH}\ 7.4\)) the protonated salt remains the dominant aqueous species. In formulation practice, liquid and immediate‑release solid oral dosage forms exploit the salt’s enhanced solubility to achieve reproducible dosing.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established numeric \(\mathrm{p}K_a\) value for this property is available in the current data context. Qualitatively, the molecule contains a single tertiary amine site that is protonated in the hydrobromide salt; therefore in aqueous solution the compound exists predominantly as the ammonium (protonated) form under neutral and mildly acidic conditions. This protonation state governs aqueous solubility, ion pairing, and the chemical form that is typically used in pharmaceutical formulations.
Reactivity and Stability
As a tertiary amine hydrobromide monohydrate, the material is classically stable under ambient conditions encountered in manufacture and routine handling but can be affected by extremes: strong bases will deprotonate the salt and release the less soluble free base, while strong oxidizing agents can oxidize tertiary amines or aromatic ethers under harsh conditions. The hydrate form indicates that thermal dehydration (loss of the crystallization water) can alter the solid form; therefore thermal processing should be validated to avoid unintended polymorphic or stoichiometric changes. Standard spectroscopic identity tests (ATR‑IR and FT‑Raman) are available for lot release and stability monitoring.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: C18H28BrNO2
- Molecular weight: 370.3 \(\mathrm{g}\,\mathrm{mol}^{-1}\) (reported as 370.3)
- Exact mass: 369.13034
- Monoisotopic mass: 369.13034
LogP and Structural Features
No experimentally established LogP (partition coefficient) value is available in the current data context. Structurally, the free base contains a methoxy‑substituted aromatic ring and a tertiary amine on a morphinan scaffold; these features impart moderate intrinsic lipophilicity. The reported TPSA of 13.5 and a low count of hydrogen bond acceptors/donors are consistent with a relatively lipophilic neutral scaffold. Conversion to the hydrobromide salt substantially increases apparent aqueous solubility and reduces effective lipophilicity in solution, which is why the hydrobromide is the preferred pharmaceutical form when aqueous delivery or dissolution control is required.
Reported computed counts and identifiers relevant to molecular properties:
- Hydrogen bond donor count: 2
- Hydrogen bond acceptor count: 3
- Rotatable bond count: 1
- Topological polar surface area (TPSA): 13.5
- Heavy atom count: 22
- Defined atom stereocenter count: 3
- Complexity: 370
Structural Identifiers (SMILES, InChI)
SMILES: CN1CC[C@@]23CCCC[C@@H]2[C@@H]1CC4=C3C=C(C=C4)OC.O.Br
InChI: InChI=1S/C18H25NO.BrH.H2O/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18;;/h6-7,12,15,17H,3-5,8-11H2,1-2H3;1H;1H2/t15-,17+,18+;;/m1../s1
InChIKey: STTADZBLEUMJRG-IKNOHUQMSA-N
(Identifiers above are reproduced as provided; SMILES and InChI are shown in plain text per structural identifier conventions.)
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 19-10-9
- UNII: 9D2RTI9KYH
- ChEBI: CHEBI:4471
- ChEMBL: CHEMBL1256818
- DSSTox Substance ID: DTXSID8045569
Synonyms and Brand-Independent Names
Common and systematic synonyms reported for the substance include:
- Dextromethorphan hydrobromide monohydrate
- Dextromethorphan hydrobromide hydrate
- Dextromethorphan (hydrobromide hydrate)
- Dextromethorphan HBr monohydrate
- d‑3‑Methoxy‑N‑methylmorphinan hydrobromide monohydrate
- (1S,9S,10S)-4‑methoxy‑17‑methyl‑17‑azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene;hydrate;hydrobromide
- (9S,13S,14S)-3‑Methoxy‑17‑methylmorphinan hydrobromide monohydrate
(The substance is listed under multiple depositor and pharmacopeial synonym variants; the subset above is representative of the names supplied for identification and pharmacopeial usage.)
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Dextromethorphan hydrobromide monohydrate is used as the active pharmaceutical ingredient (API) in antitussive preparations. As the hydrobromide salt, it is the pharmaceutically utilizable form for oral liquids, tablets and combination products where enhanced aqueous solubility and consistent bioavailability are required. In some therapeutic contexts the basic API is co‑formulated or co‑administered with agents that influence metabolic clearance to modify systemic exposure; formulation selection is driven by the salt’s solubility and solid‑state attributes.
Formulation and Development Contexts
The hydrobromide monohydrate form is selected in development to leverage salt‑induced solubility improvement and manufacturability (wet granulation, direct compression, oral solutions). The crystalline hydrate state requires control of drying and storage conditions to maintain consistent water content; this impacts assay by mass and dissolution performance. Typical dosage forms include immediate‑release tablets and oral liquids; analytical control strategies commonly include identity by IR/Raman, assay, water determination and impurity profiling.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical commercial/quality grades used in industry include pharmacopeial and regulatory grades aligned with monographs. Reported commercial grades for this substance include: EP, JP, USP. These grades indicate availability of pharmacopeial specifications suitable for pharmaceutical manufacturing and quality control.
General Quality Attributes (Qualitative Description)
Quality attributes commonly controlled for this salt hydrate include:
- Assay and related substances by validated chromatographic methods.
- Water content (to confirm monohydrate stoichiometry and control variability).
- Residual solvents (if generated during synthesis or purification).
- Particle size and polymorphic form characterization (as these influence dissolution).
- Identity confirmation by IR or Raman spectroscopy and by elemental/structural analysis.
No specific assay percentages, impurity limits or certification labels are provided in the current data context.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
As an antitussive API, the compound acts centrally at therapeutic doses; off‑label or excessive exposure can affect the central nervous system. From a handling perspective, the material should be treated as a potent pharmaceutical substance: avoid inhalation of dust, prevent dermal and ocular contact, and minimize unprotected exposure. Use appropriate engineering controls (local exhaust, containment) and personal protective equipment (gloves, eye protection, lab coat). For detailed toxicology, exposure limits and emergency measures refer to product‑specific safety documentation.
Storage and Handling Guidelines
Store the hydrobromide monohydrate in a cool, dry, well‑sealed container protected from strong oxidizers and extreme heat. Control of humidity and temperature is advisable to preserve the crystallographic hydration state. During weighing and processing implement dust control and standard pharmaceutical good manufacturing practice (GMP) hygiene. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
