Retapamulin is a semisynthetic pleuromutilin antibiotic used as a topical antibacterial active pharmaceutical ingredient. It acts by inhibiting bacterial protein synthesis through interaction with the bacterial 50S ribosomal subunit. Retapamulin is the active ingredient in ALTABAX ointment and was developed for the topical treatment of impetigo and certain superficial skin infections. (accessdata.fda.gov)
Retapamulin has the molecular formula C30H47NO4S and FDA-reported molecular weight 517.78 g/mol. It is described as a white to pale-yellow crystalline solid. (accessdata.fda.gov)
Retapamulin is a semisynthetic derivative of pleuromutilin. Its development involved fermentation-derived pleuromutilin followed by chemical modification. EMA reports that the commercial active substance is crystalline Form 1, while another polymorphic form has also been identified. Form 1 has a melting point of approximately 126°C, whereas Form 2 melts at approximately 143°C. (ema.europa.eu)
The active substance specification includes identity, HPLC assay, solid-state form by XRPD, HPLC impurities, residual solvents, water, residue on ignition, optical rotation, microbial purity and particle-size distribution. (ema.europa.eu)
| Parameter | Value |
|---|---|
| Chemical Name | Acetic acid, [[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]thio]-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl ester |
| CAS Number | 224452-66-8 |
| Molecular Formula | C30H47NO4S |
| Molecular Weight | 517.78 g/mol |
| Chemical Class | Pleuromutilin antibiotic |
| Physical Form | Crystalline solid |
| Appearance | White to pale-yellow crystalline solid |
| Commercial Crystal Form | Form 1 |
| Melting Point | Approximately 126°C for Form 1 |
| Water Solubility | 0.07 mg/mL at 25°C |
| Water Solubility Character | pH-dependent |
| Therapeutic Category | Topical antibacterial |
FDA confirms the molecular formula and molecular weight, while EMA confirms the polymorphic forms and aqueous solubility. (accessdata.fda.gov; ema.europa.eu)
Retapamulin is used as a topical antibacterial agent for susceptible bacterial skin infections.
Its established pharmaceutical application includes:
ALTABAX contains 1% retapamulin in an ointment formulation. (accessdata.fda.gov)
Retapamulin inhibits bacterial protein synthesis through interaction with the 50S ribosomal subunit, providing a mechanism distinct from many conventional topical antibiotics.
Retapamulin API requires control of chemical purity as well as solid-state characteristics. EMA's regulatory assessment confirms the use of:
The EMA assessment states that these methods were validated for their intended purposes and that production batches complied with the active-substance specification. (ema.europa.eu)
Retapamulin API manufacturing requires careful control of its pleuromutilin structure, stereochemistry, crystalline form, related substances, residual solvents and particle-size distribution.
Particular attention should be given to polymorphic form control, because EMA identified two forms and confirmed that Form 1 is the commercially used form. (ema.europa.eu)
Retapamulin should be packaged in suitable pharmaceutical-grade containers that protect the material from moisture, light and contamination.
EMA reports long-term stability studies at 25°C/60% RH for up to 36 months, intermediate studies at 30°C/65% RH, and accelerated studies at 40°C/75% RH. (ema.europa.eu)
Typical Retapamulin API documentation may include:
Retapamulin is a specialized pleuromutilin antibiotic requiring control of chemical purity, stereochemical integrity, polymorphic form and physical characteristics. A comprehensive API quality program should therefore combine chromatographic, spectroscopic and solid-state analytical methods.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.5% |
| Melting Point | Approximately 126°C |