Phenylephrine Hydrochloride, commonly referred to as Phenylephrine HCl, is a well-established pharmaceutical active ingredient belonging to the sympathomimetic and alpha-adrenergic agonist class. It is the hydrochloride salt of phenylephrine and is widely incorporated into pharmaceutical formulations requiring vasoconstrictor, nasal decongestant or mydriatic activity. Phenylephrine primarily stimulates alpha-1 adrenergic receptors, producing contraction of vascular smooth muscle and resulting in vasoconstriction.
Phenylephrine Hydrochloride is identified by CAS Number 61-76-7, with the molecular formula C9H14ClNO2 and molecular weight 203.67 g/mol. The API is chemically classified as a substituted phenylethanolamine and contains a stereogenic center. The pharmaceutical substance corresponds to the R-enantiomer, making stereochemical identity an important part of pharmaceutical quality control.
Phenylephrine HCl is used in a variety of pharmaceutical dosage forms because of its established pharmacological properties and well-defined analytical profile. It is particularly relevant to products intended for temporary relief of nasal congestion and to ophthalmic formulations where controlled pupil dilation is required.
The hydrochloride salt is commonly selected for pharmaceutical formulation because it provides a defined crystalline active substance suitable for controlled manufacturing. API quality is evaluated through identity, assay, related substances, optical rotation, moisture and other applicable physicochemical parameters.
For pharmaceutical manufacturers, consistent Phenylephrine HCl quality is important because variations in active-content, stereochemical characteristics or impurity levels can affect the consistency of the finished dosage form.
| Parameter | Details |
|---|---|
| Product Name | Phenylephrine Hydrochloride |
| Common Name | Phenylephrine HCl |
| CAS Number | 61-76-7 |
| Molecular Formula | C9H14ClNO2 |
| Molecular Weight | 203.67 g/mol |
| Chemical Class | Phenylethanolamine |
| Pharmacological Class | Alpha-1 adrenergic agonist |
| Therapeutic Category | Sympathomimetic / decongestant |
| ATC Code | R01AA04 |
| Physical Form | Solid |
| Appearance | White or practically white powder |
| Stereochemical Form | R-configuration |
| Specific Rotation | −43° to −47° |
| Water Solubility | Freely soluble |
Phenylephrine Hydrochloride has several pharmaceutical applications based on its alpha-adrenergic activity. Its vasoconstrictive properties make it suitable for topical and systemic pharmaceutical formulations, depending on the intended indication and regulatory approval.
Phenylephrine HCl is used in nasal pharmaceutical products as a topical nasal decongestant. Alpha-adrenergic stimulation causes vasoconstriction of nasal mucosal blood vessels, helping reduce mucosal swelling and nasal obstruction.
Phenylephrine Hydrochloride is also used in ophthalmic preparations. Its alpha-adrenergic activity can produce mydriasis, making the API relevant to ophthalmic products designed for pupil dilation.
Depending on regulatory authorization and formulation design, Phenylephrine Hydrochloride may also be incorporated into other pharmaceutical dosage forms where its vasoconstrictor properties are therapeutically appropriate.
The exact concentration, dosage form and route of administration depend on the finished pharmaceutical product and applicable regulatory requirements.
Manufacturing Phenylephrine Hydrochloride requires appropriate control of chemical synthesis, purification, crystallization and drying processes. Since the active substance has a defined stereochemical form, manufacturing and analytical controls should also ensure that the desired stereochemical characteristics are maintained.
A pharmaceutical-grade manufacturing process generally incorporates controls for:
Process consistency is important for achieving reproducible batches and maintaining compliance with the applicable registered API specification.
Identification testing is an essential component of Phenylephrine Hydrochloride quality control. Current USP requirements include multiple identity approaches, including infrared absorption, chloride identification and chromatographic retention-time comparison.
Using multiple identification characteristics provides greater assurance that the tested material corresponds to Phenylephrine Hydrochloride and not another structurally related phenylethanolamine.
Phenylephrine HCl has a well-defined current USP assay requirement. The USP assay specification is 98.0% to 102.0% on the dried basis.
The USP assay uses liquid chromatography with UV detection. This makes HPLC/LC an appropriate description for the assay field in a CMS specification, unlike APIs whose pharmacopoeial assay is performed exclusively through acid-base or nonaqueous titration.
For pharmaceutical API release, the assay method should be validated for specificity, precision, accuracy, linearity and range according to the applicable analytical validation requirements.
Related-substance control is particularly important for pharmaceutical APIs because impurities can originate from starting materials, intermediates, side reactions or degradation.
The current USP specification includes specific controls for several Phenylephrine-related impurities. The specified limits include:
These controls provide a defined chromatographic purity profile for Phenylephrine Hydrochloride API.
Optical rotation is an important characteristic of Phenylephrine Hydrochloride because the pharmaceutical substance has a defined stereochemical configuration.
The current USP specification gives a specific rotation of −43° to −47°, measured using the specified aqueous test solution.
Optical rotation testing can therefore serve as an additional quality-control parameter for confirming the stereochemical characteristics of the API. It should be used together with appropriate identity testing rather than as a standalone identity test.
Moisture control is another important aspect of Phenylephrine Hydrochloride API quality. The current USP specification establishes Loss on Drying at NMT 1.0%.
Controlled drying helps maintain consistent API characteristics and minimizes variability that could affect assay calculation on the dried basis. Manufacturing and packaging processes should be designed to prevent unnecessary moisture uptake following drying.
The current USP specification establishes Residue on Ignition at NMT 0.2% for Phenylephrine Hydrochloride.
This test provides a measure of inorganic residue remaining after ignition and can support control over inorganic materials introduced during manufacturing or processing.
Sulfate is also controlled in the current USP specification, with a limit of NMT 0.20%.
Appropriate control of inorganic impurities contributes to the overall chemical purity profile of the API and supports consistency between manufacturing batches.
A comprehensive quality-control program for Phenylephrine Hydrochloride can include:
The final release specification should always correspond to the applicable current pharmacopoeial standard or registered product specification.
Phenylephrine HCl can be characterized using several analytical techniques. HPLC/LC is particularly important for assay and related-substance testing. Infrared spectroscopy provides an important identity tool, while optical rotation contributes information about stereochemical characteristics.
For impurity analysis, chromatographic resolution is important because structurally related compounds can have similar chemical properties. A properly validated chromatographic procedure should demonstrate adequate separation of Phenylephrine from specified related compounds.
Analytical methods used for pharmaceutical release should be validated and controlled under the applicable quality system.
Phenylephrine Hydrochloride should be packaged in appropriate pharmaceutical-grade containers capable of protecting the API from contamination and environmental exposure.
Packaging should maintain the required quality throughout transportation and storage. The current USP monograph specifies tight, light-resistant containers for Phenylephrine Hydrochloride.
Suitable labeling can include:
Phenylephrine Hydrochloride should be stored under controlled pharmaceutical conditions. The current USP information specifies storage at 25°C, with permitted excursions between 15°C and 30°C, in tight, light-resistant containers.
Storage areas should be clean, dry and appropriately controlled to protect the API from unsuitable environmental conditions.
For pharmaceutical development and manufacturing, Phenylephrine Hydrochloride API may be supported by appropriate quality and regulatory documentation, including:
The documentation package should reflect the intended pharmaceutical application and destination-market requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.20% |
| Specific Rotation | −43° to −47° |