Procaine benzylpenicillin (penicillin G procaine, CAS 54-35-3, C29H38N4O6S, MW 570.7) is a sustained-release salt of benzylpenicillin formed with procaine. It is one of the most widely used injectable antibiotics in veterinary medicine and remains a reference sterile API for long-acting penicillin therapy. This guide covers its chemistry, production, specifications and applications.
1. What Is Procaine Benzylpenicillin?
Benzylpenicillin (penicillin G) is a beta-lactam antibiotic active mainly against Gram-positive bacteria. Its procaine salt combines one molecule of benzylpenicillin with one of procaine, forming a sparingly soluble salt that releases penicillin G slowly after intramuscular injection – giving sustained blood levels over 24-48 hours with a single dose.
2. Chemistry and Properties
| Property | Value |
|---|---|
| Molecular formula | C29H38N4O6S |
| Molecular weight | 570.7 g/mol |
| Composition | Procaine + benzylpenicillin salt (procaine 39-42%) |
| Appearance | White or almost white crystalline powder |
| Solubility | Slightly soluble in water; sparingly soluble in ethanol (96%) |
| pKa / stability | Beta-lactam ring hydrolyses in strong acid/alkali; keep dry and cool |
3. Production Technology
Commercial production follows classic penicillin salt chemistry:
- Benzylpenicillin fermentation – penicillin G is produced by fermentation of Penicillium chrysogenum with phenylacetic acid side-chain precursor.
- Salt formation – benzylpenicillin (acid form) is combined with procaine base to precipitate procaine benzylpenicillin with controlled crystal habit.
- Purification and micronization – washing, sterile filtration/crystallization, and micronization to a narrow particle-size distribution.
- Lecithin coating (optional) – particles are coated with ~1% lecithin to improve suspension behaviour and syringeability of long-acting injectables.
- Sterile filling – final product is handled aseptically to meet sterility and endotoxin limits.
4. Specifications and Grades
This grade is sterile, micronized and lecithin-coated (approx. 1%), meeting Ph. Eur. 12th Edition. Key acceptance points: assay of procaine benzylpenicillin 96.0-102.0% and procaine 39.0-42.0% (anhydrous); water 2.8-4.2%; pH 5.0-7.5; individual impurities per Ph. Eur. limits (A-J controlled, total impurities ≤2.0%); residual solvents n-butanol and ethyl acetate ≤5000 ppm; bacterial endotoxins ≤0.10 IU/mg; sterility complies; particle size 50% <8 μm (90% <25 μm per customer requirement).
5. Applications Overview
- Veterinary medicine – injectable long-acting penicillin for cattle, swine, sheep and poultry infections.
- Human pharmaceutical API – sustained penicillin therapy (historical and specialty indications).
- Combination formulations – with benzathine penicillin or dihydrostreptomycin for extended spectra.
6. Application Details
6.1 Veterinary long-acting penicillin
Procaine penicillin G is the standard single-dose treatment for many Gram-positive infections in livestock (e.g. mastitis, pneumonia, erysipelas, foot infections). The sparingly soluble salt maintains therapeutic penicillin levels for roughly 24-48 hours, reducing handling stress and labour. The micronized lecithin-coated form is preferred for ready-to-use aqueous suspensions with good syringeability.
6.2 Sterile API supply
For pharmaceutical and high-end veterinary manufacturers, sterile micronized grade is filled aseptically; tight control of particle size, endotoxins and sterility is essential.
7. Industry Landscape
Major penicillin G producers operate large fermentation plants; sterile salt conversion (procaine/benzathine salts, micronization, coating) is a distinct specialty step often outsourced. Buyers should qualify suppliers on Ph. Eur./USP compliance, impurity profile, particle-size capability and sterility assurance.
8. Buying Guide
- Specify pharmacopoeia (Ph. Eur. 12 / USP), sterile grade, particle size and coating (1% lecithin) on the order.
- Request COA with assay (both procaine and benzylpenicillin), impurity profile, water, residual solvents, endotoxins and sterility certificate.
- Confirm packaging suitable for aseptic processing and cold-chain requirements if any.
- Qualify the supplier with change control and regulatory documentation (CEP/DMF if required).
9. Safety and Regulatory Notes
- Penicillins can cause serious allergic reactions – handle with care, avoid dust inhalation and skin contact.
- Requires appropriate manufacturing authorization for sterile APIs; export subject to relevant pharmaceutical export rules per destination.
- Store sealed, cool, dry and protected from light.
10. FAQ
What is the difference between procaine penicillin and benzathine penicillin?
Both are long-acting salts of penicillin G. Procaine penicillin gives therapeutic levels for about 24-48 hours; benzathine penicillin releases much more slowly (days to weeks). They are sometimes combined.
Why is lecithin coating used?
Lecithin coating of micronized particles improves wettability and suspension stability, reduces caking, and makes long-acting injectable suspensions easier to draw and inject.
11. References and Further Reading
- PubChem entry for penicillin G procaine (CID 5903).
- Ph. Eur. 12th Edition monograph, Procaine benzylpenicillin.
- Supplier COA, sterility certificate and MSDS for the specific grade quoted.
This article is published for industrial and technical reference by PolyblueChem. Verify all values against the supplier’s COA and the applicable pharmacopoeia before specification.
PolyblueChem supplies procaine benzylpenicillin (CAS 54-35-3) sterile micronized lecithin-coated grade with COA and sterility documentation. Contact us for specifications and quotations.