Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin

Rectal drug administration could offer advantages in the delivery of medicines for children by avoiding swallowability issues, improving stability and enabling administration by caregivers. This study aimed to evaluate the rectal bioavailability of hollow-type suppositories (HTS) and understand the effect of two chemical forms of amoxicillin: amoxicillin sodium (AS) or amoxicillin trihydrate (AMT). HTS were prepared by incorporating a lipophilic core containing the antibiotic with a polyethylene glycol (PEG) shell. Formulations were characterised in vitro, and the absolute bioavailability was determined in a rabbit model, while drug–base interactions were evaluated using X-ray diffraction crystallography (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy.

The in vitro amoxicillin release from AMT HTS was delayed, taking 27.3 ± 4.9 h to release 50% drug compared with 1.7 h for the AS HTS, likely due to solubility differences between AMT and AS. The presence of orthorhombic AMT and anhydrous AS crystals in respective HTS was confirmed via XRD and DSC. PEG shells were able to protect the drug chemical stability when stored at 25 °C/60% RH. Despite the difference in their in vitro release rates, a similar rectal bioavailability was found in both forms of amoxicillin (absolute bioavailability 68.2 ± 6.6% vs. 72.8 ± 32.2% for AMT HTS and AS HTS, respectively; p = 0.9682). Both HTS formulations showed little or no irritation to the rectal mucosa following a single dose.

Materials

AS (>87% purity) and AMT (>99% purity) were both purchased from Alfa Aesar by Thermo Fisher Scientific (Haverhill, MA, USA). PEG 1500 and dialysis bags with a molecular weight cut-off (MWCO) of 14,000 Da were purchased from Sigma Aldrich (St. Louis, MO, USA). Suppocire NA 15 suppositories were a gift from Gattefossé SAS, Saint-Priest, France. Reagent-grade chemicals (acetic acid, sodium acetate, sodium chloride, sodium/potassium dihydrogen phosphate and disodium hydrogen phosphate) were used in the preparation of buffer media and purchased from either Merck or Thermo Fisher Scientific (Auckland, New Zealand). Acetonitrile and methanol used in the chromatographic analysis were high-performance liquid chromatography (HPLC)-grade. Milli-Q water was obtained from a Millipak water dispenser (Millipore, Burlington, MA, USA, 0.22 µm).

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Purohit, T.J.; Amirapu, S.; Wu, Z.; Hanning, S.M. Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin. Pharmaceutics 2023, 15, 1865., https://doi.org/10.3390/pharmaceutics15071865