Amoxicillin sodium

Amoxicillin trihydrate is a white or almost white crystalline powder. Amoxicillin sodium salt is a white or almost white powder, sometimes with a pinkish tinge. As normally produced it is amorphous and hygroscopic. Freshly prepared aqueous solutions may show a transient pink colouration [2], Both compounds may have the slightly sulphurous odour that is typical of many penicillins. 

Amoxicillin sodium salt is manufactured either by suspension of the trihydrate in water or a mixture of water and an alcohol such as isopropanol, dissolution by addition of sodium hydroxide solution and isolation by lyophilisation or spray drying, or by a precipitation method in which sodium ethylhexanoate in a solvent such as isopropanol is added to amoxicillin dissolved in an organic solvent by addition of an amine such as triethylamine. 

Amoxicillin sodium salt is normally prepared in an amorphous form. An anhydrous crystalline form can be obtained [17] by removal of solvent from various solvates, either in the solid state or by displacement in solution with a solvent of lower dielectric constant. 

Amoxicillin sodium salt, in its usual amorphous form, gives a featureless diffractogram. 

Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA) of amoxicillin trihydrate showed loss of the water of crystallisation from about 50 to 150 °C followed by decomposition of the amoxicillin from about 160°C upwards [18], DSC and TGA of amoxicillin sodium salt in an oxygen atmosphere showed loss of water at about 100°C and thermal decomposition in multiple events from about 200 to 500°C [19]. The techniques are of little practical value for these compounds. 

IR spectra of amoxicillin trihydrate and amoxicillin sodium salt in a potassium bromide disc are shown in Figures 2 and 3 respectively. The frequencies and assignments of significant bands are listed below. 

Figure 3. Infrared Spectrum of Amoxicillin Sodium Salt...

Solid state C-13 NMR spectra of amoxicillin trihydrate and other penicillins have been used to compare thiazolidine ring conformations in the solution and solid states [24], The results indicated rapid interconversion between the S out of plane and the C3 out of plane conformations in solution, with an equilibrium ratio of 74 to 26 for solutions of amoxicillin sodium salt. 

Hie stability of amoxicillin sodium salt in various intravenous infusion fluids has been studied [33-35], Degradation was faster at the higher amoxicillin concentrations [33] and particularly in fluids containing dextrose, dextran or sorbitol [33-35], Other studies also showed a deleterious effect of carbohydrates and alcohols on the stability of amoxicillin in solution [36,37],... 

Degradation of amoxicillin in aqueous solution containing phosphate [45], sorbitol and zinc sulphate [46] or diethanolamine and zinc sulphate [47] gave a product which was assumed from its spectroscopic properties, and by analogy with ampicillin degradation, to be the piperazine-2,5-dione, VI. This was subsequently confirmed by characterisation of the isolated product [48,49], which was shown [48] to be formed in significant amount on degradation of concentrated aqueous solutions of amoxicillin sodium... 

Amoxicillin dimer, present as an impurity in amoxicillin sodium salt, was isolated and characterised as VII [SO], More detailed characterisation, together with data on amoxicillin trimer, was given in [48], Both compounds were isolated from an aged 20% solution of amoxicillin sodium salt, chromatographic analysis of which also indicated the presence of a tetramer and the penicilloates corresponding to these three oligomers. 

TLC systems that separate amoxicillin from its major degradation products were used to monitor the purity of amoxicillin sodium salt during process development [107] and ofisolated degradation products [48],... 

Figure 49. Temperature dependence of degradation rate of amoxicillin sodium in saline (a, ) and 5% glucose solution ( ). (Reproduced from Ref. 352 with permission.)...

Sample preparation Dissolve 200 mg amoxicillin trihydrate in 8 mL 200 mM pH 11.0 phosphate buffer, add 10 mL 70 mg/L sulfamethazine in solvent, make up to 20 mL with solvent, inject an aliquot within 1 min. Dissolve 200 mg amoxicillin sodium salt in 8 mL solvent, add 10 mL 70 mg/L sulfamethazine in solvent, make up to 20 mL with solvent, inject an aliquot within 1 min. (Solvent was MeOH 200 mM pH 7.0 potassium phosphate buffer water 5 5 90.)... 

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