Amoxicillin trihydrate
[CAS# 61336-70-7]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Amoxicillin trihydrate
• Synonyms: 6-[2-Amino-2-(4-hydroxyphenyl)-acetyl]amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate
• Molecular Formula: C₁₆H₁₉N₃O₅S.3(H₂O)
• Molecular Weight: 419.45
• CAS Registry Number: 61336-70-7
• EC Number: 612-127-4
• SMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=C(C=C3)O)N)C(=O)O)C.O.O.O

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H317-H334-H400-H411
• Safety Statements: P233-P260-P261-P271-P272-P273-P280-P284-P302+P352-P304+P340-P321-P333+P317-P342+P316-P362+P364-P391-P403-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Respiratory sensitization	Resp. Sens.	1	H334
Skin sensitization	Skin Sens.	1	H317
Respiratory sensitization	Resp. Sens.	1A	H334
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

Amoxicillin trihydrate is a crystalline form of the antibiotic amoxicillin, a semisynthetic β-lactam antimicrobial agent derived from penicillin. It belongs to the aminopenicillin subclass and exhibits a broad spectrum of activity against both Gram-positive and some Gram-negative bacteria. The compound is a hydrate form, specifically containing three molecules of water per molecule of amoxicillin. Its molecular formula is C₁₆H₁₉N₃O₅S·3H₂O.

Amoxicillin was developed in the 1960s by researchers at Beecham Research Laboratories in the United Kingdom. It was introduced as an improvement upon earlier penicillin derivatives, particularly ampicillin. The goal was to develop an orally effective antibiotic with improved absorption and a broader antibacterial spectrum. The introduction of the para-hydroxyphenyl group into the structure of ampicillin led to amoxicillin, which demonstrated superior oral bioavailability. It was patented in 1971 and became widely available in the early 1970s under various brand names.

The trihydrate form is the most commonly used solid-state formulation in oral dosage forms such as capsules, tablets, and suspensions. It is preferred for its stability, ease of formulation, and acceptable solubility in aqueous media. The crystalline trihydrate ensures consistent drug performance and has been thoroughly characterized in pharmaceutical research and regulatory documentation.

Amoxicillin trihydrate functions by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), which are involved in the final stages of peptidoglycan crosslinking during cell wall formation. This action results in the weakening of the bacterial cell wall, leading to cell lysis and death, particularly in actively growing bacteria.

This antibiotic is used extensively in clinical practice for the treatment of a wide range of bacterial infections. Indications include infections of the respiratory tract (such as pharyngitis, sinusitis, and bronchitis), urinary tract infections, skin and soft tissue infections, and otitis media. It is also a component of combination therapy for the eradication of *Helicobacter pylori* in patients with gastric ulcers, commonly paired with clarithromycin and a proton pump inhibitor.

Amoxicillin trihydrate exhibits good oral absorption, with peak plasma concentrations typically reached within 1 to 2 hours after administration. The presence of food does not significantly affect its bioavailability. It is widely distributed in body tissues and fluids and is primarily eliminated via renal excretion in unchanged form.

Despite its broad utility, amoxicillin trihydrate is susceptible to degradation by β-lactamase enzymes produced by resistant bacterial strains. To overcome this, it is often co-formulated with β-lactamase inhibitors such as clavulanic acid. The combination of amoxicillin and clavulanate potassium significantly extends the antibacterial spectrum by neutralizing β-lactamase activity.

Amoxicillin trihydrate is included in the World Health Organization’s Model List of Essential Medicines, reflecting its critical role in the treatment of infectious diseases. It is available globally and is included in many national formularies. Its safety profile is well-documented, with the most common adverse effects being gastrointestinal in nature, such as nausea, diarrhea, and rash. Hypersensitivity reactions, including anaphylaxis, have been reported in individuals with penicillin allergies.

Quality control and pharmaceutical manufacturing of amoxicillin trihydrate are regulated by pharmacopeial standards, including those of the USP, BP, and EP. Characterization includes assessments of crystallinity, particle size, purity, and stability under storage conditions. These parameters are essential for ensuring the efficacy and shelf life of the final dosage forms.

Amoxicillin trihydrate remains a foundational antibiotic in both primary and hospital care settings. Its widespread acceptance and use reflect its therapeutic effectiveness, cost-efficiency, and relatively low resistance rate in comparison to other oral antibiotics. Its continued utility is supported by extensive clinical experience and robust pharmaceutical data.

References

2024. Effectiveness and safety of vonoprazan and amoxicillin dual regimen with Saccharomyces boulardii supplements on eradication of Helicobacter pylori. BMC Gastroenterology, 24(1).
DOI: 10.1186/s12876-024-03524-0

2024. Ten-day versus 14-day vonoprazan-amoxicillin high-dose dual therapy for Helicobacter pylori eradication in China: A multicenter, open-label, randomized study. Journal of Gastroenterology and Hepatology, 39(11).
DOI: 10.1111/jgh.16761

2024. Amoxicillin-associated hemorrhagic colitis: A case report and literature review. Medicine, 103(49).
DOI: 10.1097/md.0000000000040800