Phenoxymethylpenicillin, commonly known as Penicillin V or Penicillin VK, is a narrow-spectrum β-lactam penicillin antibiotic used as an active pharmaceutical ingredient in oral antibacterial formulations. It is a naturally derived penicillin produced by certain strains of Penicillium or obtained through appropriate manufacturing processes. Phenoxymethylpenicillin is particularly suitable for oral administration because it is more acid-stable than benzylpenicillin (Penicillin G).
The API has the chemical formula C₁₆H₁₈N₂O₅S, molecular weight 350.4 g/mol, and CAS Number 87-08-1. The compound is the free-acid form of phenoxymethylpenicillin. The corresponding potassium salt, Phenoxymethylpenicillin Potassium, is a distinct API form with CAS 132-98-9 and molecular weight approximately 388.5 g/mol. These forms should not be interchanged when entering pharmaceutical product or CMS data.
Phenoxymethylpenicillin is a narrow-spectrum antibiotic active primarily against susceptible Gram-positive bacteria and selected other susceptible organisms. It has historically been used for infections involving the respiratory tract, skin and soft tissues, and other infections caused by penicillin-sensitive microorganisms. It has also been used in certain prophylactic applications where clinically appropriate.
As a β-lactam antibiotic, phenoxymethylpenicillin acts by interfering with bacterial cell-wall synthesis. Its antibacterial activity is associated with inhibition of penicillin-binding proteins and disruption of the peptidoglycan cross-linking process, ultimately leading to bacterial cell death in susceptible organisms.
Phenoxymethylpenicillin is chemically defined as (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid. It possesses the characteristic β-lactam ring structure of penicillin antibiotics and contains defined stereochemistry at the penicillin nucleus.
The API is described as a white or almost white, slightly hygroscopic crystalline powder. The European Pharmacopoeia/British Pharmacopoeia monograph describes it as very slightly soluble in water and soluble in ethanol (96%). The International Pharmacopoeia provides a more specific solubility description, reporting approximately 1 part in 1700 parts of water and approximately 1 part in 7 parts of ethanol.
Because phenoxymethylpenicillin is susceptible to degradation under humid conditions, appropriate packaging and storage controls are important. The International Pharmacopoeia recommends storage in a tightly closed container protected from light and notes that degradation can accelerate with increased humidity and temperature.
Phenoxymethylpenicillin has an established European Pharmacopoeia/British Pharmacopoeia monograph. The BP 2025 monograph specifies a content range of 95.0% to 102.0%, calculated on the anhydrous substance, for the sum of phenoxymethylpenicillin and 4-hydroxyphenoxymethylpenicillin.
The monograph also specifies pH 2.4–4.0 and a specific optical rotation of +186° to +200°, calculated on the anhydrous substance. Related substances are evaluated by liquid chromatography. These are particularly useful numerical values for CMS specification fields because they are associated with a recognized pharmacopoeial monograph rather than generic API assumptions.
The related-substance profile includes specified impurities such as benzylpenicillin, phenoxyacetic acid, 6-aminopenicillanic acid, 4-hydroxyphenoxymethylpenicillin, penicilloic acids, and penilloic acids. Current accessible pharmacopoeial material identifies specific limits for these impurities, but the exact applicable limits should be matched to the pharmacopoeial edition being claimed for the product rather than mixing limits from different editions.
Phenoxymethylpenicillin API manufacturing requires stringent control of identity, potency, degradation products, moisture, optical purity/stereochemistry, and microbiological quality where applicable. Because β-lactam antibiotics can undergo hydrolytic degradation, moisture and storage conditions are important quality considerations.
For pharmaceutical manufacturers, the exact API form should always be stated clearly. Phenoxymethylpenicillin (free acid), CAS 87-08-1, MW 350.4 g/mol is different from Phenoxymethylpenicillin Potassium, CAS 132-98-9, MW 388.5 g/mol.
Phenoxymethylpenicillin therefore represents a well-established oral penicillin API with recognized pharmacopoeial standards, defined chemical identity, controlled impurity profile, and established pharmaceutical applications in antibacterial formulations.
| 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 0.1% |
| pH (1% Solution) | 2.4–4.0 |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 0.5% |