What is Amoxicillin Trihydrate?
Amoxicillin trihydrate is the crystalline hydrated form of amoxicillin—a semisynthetic penicillin antibiotic—containing three water molecules per molecule of the active drug. This is the standard pharmaceutical formulation used in oral preparations worldwide 1.
Chemical Structure and Formulation
Amoxicillin trihydrate has the molecular formula C₁₆H₁₉N₃O₅S·3H₂O with a molecular weight of 419.45 1. The "trihydrate" designation refers to the three water molecules that are incorporated into the crystal structure during manufacturing. This hydrated form provides:
- Enhanced stability during storage
- Consistent dissolution characteristics
- Predictable bioavailability when administered orally
The trihydrate form is chemically described as (2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido]-3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate 1.
Available Formulations
Amoxicillin trihydrate is manufactured in multiple oral dosage forms 1:
- Oral suspensions: 125 mg/5 mL and 250 mg/5 mL (each dose expressed as amoxicillin content, not including the water molecules)
- Capsules and tablets: Various strengths up to 875 mg
- Each 5 mL of reconstituted suspension contains small amounts of sodium (0.11-0.15 mEq)
Clinical Significance
The trihydrate form is functionally equivalent to other amoxicillin salts in terms of antibacterial activity. When prescribing or dispensing, doses are always expressed as the amount of active amoxicillin, not the trihydrate salt 1. For example, "amoxicillin 500 mg" refers to 500 mg of the active antibiotic, even though the actual trihydrate powder weighs more due to the water molecules.
Pharmacokinetic Properties
Amoxicillin trihydrate demonstrates 1:
- Excellent oral bioavailability (stable in gastric acid)
- Rapid absorption with peak levels at 1-2 hours
- Approximately 20% protein binding in serum
- Renal elimination with a half-life of approximately 61 minutes in patients with normal kidney function
Biopharmaceutics Classification
Amoxicillin trihydrate at doses ≤875 mg is classified as BCS Class I (high solubility, high permeability), while doses of 1000 mg fall into BCS Class II, and doses exceeding 1000 mg are BCS Class IV 2. This classification impacts regulatory requirements for bioequivalence testing.
Manufacturing Considerations
The crystallization process and pH control during manufacturing significantly affect the physical properties of amoxicillin trihydrate 3. Powder pH values between 4.39-4.97 influence crystal size, crystallinity, and thermal stability, though all compliant batches meet pharmacopeial purity standards.