Pholcodine CAS Number 509-67-1 identifies pholcodine, an opioid-derived antitussive active pharmaceutical ingredient (API) historically used in cough-suppressant formulations. Pholcodine is a morphinan alkaloid structurally related to morphine and is characterized by a morpholinoethyl ether substitution on the morphinan nucleus. PubChem identifies pholcodine with the molecular formula C₂₃H₃₀N₂O₄ and molecular weight 398.50 g/mol for the anhydrous active moiety.
For pharmaceutical applications, however, the pharmacopoeial material is commonly identified as Pholcodine Monohydrate, with the formula C₂₃H₃₀N₂O₄·H₂O and molecular weight 416.5 g/mol. The Indian Pharmacopoeia monograph identifies pholcodine as the monohydrate and specifies its assay on the dried basis.
Pholcodine is chemically described as 7,8-didehydro-4,5α-epoxy-17-methyl-3-[2-(morpholin-4-yl)ethoxy]morphinan-6α-ol monohydrate in the Indian Pharmacopoeia. The API contains multiple defined stereocentres characteristic of its morphinan structure.
The distinction between anhydrous pholcodine and pholcodine monohydrate is important for pharmaceutical documentation. The anhydrous molecular weight is approximately 398.50 g/mol, whereas the monohydrate molecular weight is 416.5 g/mol. Assay calculations must therefore specify the applicable basis and chemical form.
Pholcodine has historically been used as an opioid cough suppressant for the symptomatic treatment of non-productive or dry cough. Its antitussive action is associated with activity at opioid receptors in the central nervous system. Compared with stronger opioid analgesics, pholcodine has historically been characterized primarily for cough suppression, with relatively limited analgesic activity.
Pholcodine has been incorporated into oral pharmaceutical preparations such as cough syrups, oral solutions, and linctuses. The British Pharmacopoeia continues to recognize pholcodine-related pharmaceutical texts, including Pholcodine Linctus, while regulatory status and availability vary substantially between countries.
Pholcodine monohydrate is described pharmacopoeially as a white or almost white crystalline powder. The Indian Pharmacopoeia specifies storage protected from moisture, reflecting the importance of controlling hydration and environmental exposure during API handling.
The API is associated with measurable optical activity because of its defined stereochemical structure. The Indian Pharmacopoeia specifies a specific optical rotation of −94.0° to −98.0°, determined at 20°C using a 2.0% w/v solution in ethanol (95%).
Pholcodine has a recognized pharmacopoeial quality framework. The Indian Pharmacopoeia 2010 monograph specifies that pholcodine contains not less than 98.0% and not more than 101.0% of C₂₃H₃₀N₂O₄, calculated on the dried basis. It also specifies loss on drying of 3.9–4.5%, reflecting its monohydrate character, and sulphated ash not more than 0.1%.
The monograph includes infrared identification, ultraviolet identification, a chemical identification reaction, specific optical rotation, related-substance testing by thin-layer chromatography, and assay by non-aqueous titration. These requirements should be distinguished from generic HPLC specifications because the pharmacopoeial assay method itself is potentiometric titration with 0.1 M perchloric acid.
Pholcodine API manufacturing requires stringent control of identity, stereochemical integrity, assay, moisture, related substances, inorganic residue, and storage conditions. Because the pharmaceutical form is commonly the monohydrate, moisture and hydration-state control are particularly relevant to batch consistency.
For a CMS product page, pharmacopoeial values should be used where they are directly verified. The 98.0–101.0% assay, 3.9–4.5% loss on drying, NMT 0.1% sulphated ash, and −94.0° to −98.0° specific rotation can be presented as IP 2010 values.
For fields such as individual impurity limits, total impurities, heavy metals, pH, and residual solvents, a numerical value should not be invented when the publicly verified monograph information does not provide a universal limit. Such parameters should remain specification-dependent or be linked to the applicable approved specification.
Pholcodine is an opioid-related substance, and its regulatory status differs significantly between jurisdictions. PubChem notes that it is controlled or unavailable in some countries, while historical pharmaceutical use exists in other markets.
Consequently, pharmaceutical manufacturers and formulation developers should verify the regulatory status, permitted use, import/export requirements, and applicable controlled-substance regulations in the intended market before commercial use.
Pholcodine therefore represents a well-defined opioid antitussive API with CAS Number 509-67-1, an established monohydrate pharmaceutical form, molecular weight 416.5 g/mol for the monohydrate, and recognized pharmacopoeial quality requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | 3.9–4.5% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |
| Specific Rotation | −94.0° to −98.0° at 20°C |