Introduction

Amoxicillin trihydrate is a semisynthetic broad-spectrum antibiotic classified as an aminopenicillin. The IUPAC Name is (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; trihydrate[1].

Different types of Amoxicillin

Amoxicillin trihydrate and its salts are included in several pharmacopoeia, for example, the British Pharmacopoeia, in Martindale, The Extra Pharmacopoeia, and the International Pharmacopoeia. The molecular formula of Amoxicillin is C16H19N3O5S (anhydrous substance), and its molecular weight is 365.40 g/mol. The molecular weight of amoxicillin trihydrate, C16H19N3O5S.3H2O, is 419.4 g/mol. Amoxicillin is available as a white, almost white, or slightly pinkish-coloured powder or a crystalline solid. The melting point of Amoxicillin is 194 ℃, although, under a helium atmosphere, it is reported to be 190.1 ℃. Anhydrous Amoxicillin shows a specific optical rotation of +290 to +315. Amoxicillin is also available in pharmaceutical preparations in the salt form, amoxicillin sodium.

Chemical property

Amoxicillin trihydrate is slightly soluble in water, very slightly soluble in ethanol (96%), and practically insoluble in fatty oils. It dissolves in dilute acids and dilute solutions of alkali hydroxides. Amoxicillin trihydrate is slightly soluble in water and methanol R; very slightly soluble in ethanol (~750 g/l) TS, ether R, and fatty oils; and soluble in dilute acids and dilute solutions of alkali hydroxides. The frequencies and assignments of significant bands and IR spectra of Amoxicillin trihydrate in a potassium bromide disc is given below.

Mechanism of action

Therapeutically, Amoxicillin is used as a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. In general, Amoxicillin is produced as amoxicillin trihydrate. During the crystallization of Amoxicillin from its solution form, it picks up three molecules of water as water of crystallization, although anhydrous Amoxicillin can also be made and used.

Amoxicillin induces lysis in bacterial cells by binding to the 1A penicillin-binding protein of the cell wall. This binding inactivates the protein and prevents proper binding of peptidoglycan chains, thus weakening the cell wall to the eventual point of failure. Amoxicillin is notably stable in the presence of gastric acid.

Uses

In clinical medicine, Amoxicillin is widely used to treat various bacterial infections. Infections typically indicated using Amoxicillin include skin, throat, ear, nasal and urinary tract infections. Administered on its own, Amoxicillin is only effective against beta-lactamase-negative pathogens. In research settings, Amoxicillin is often used in studies of antibiotic resistance due to its widespread use in clinical medicine.

Dosage Forms

Solid oral dosage forms containing amoxicillin trihydrate 250 mg and 500 mg are listed in the 19th list of Essential Medicines (2015) by the WHO[2]. Products of amoxicillin trihydrate listed in pharmacopoeias include capsules (250 mg, 500 mg), tablets (200- 1000 mg), chewable tablets (125-500 mg), dispersible tablets (750 mg), oral suspension and dry powder for oral suspension (50-400 mg/mL, 3 g). However, for the vast majority of clinical indications, solid oral dosage forms containing either 250 mg or 500 mg amoxicillin trihydrate are used. The aforementioned doses are based on the milligram amount of amoxicillin trihydrate.

References

[1] Product Information Report: Amoxicillin (usp-pqm.org) https://www.usp-pqm.org/sites/default/files/pqms/article/amoxicillin-pir-jul2018.pdf

[2] Dhanusha Thambavita . “Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate.” Journal of pharmaceutical sciences 106 10 (2017): Pages 2930-2945.