Rectal bioavailability of amoxicillin sodium in rabbits: Effects of suppository base and drug dose

• Published in: Journal of controlled release Vol. 338; pp. 858 - 869
• Main Authors: Purohit, Trusha J., Hanning, Sara M., Amirapu, Satya, Wu, Zimei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.10.2021
• Subjects: Absolute bioavailability; Amoxicillin; Drug release kinetics; In vitro – In vivo correlation (IVIVC); Rectal drug delivery; Suppositories; In vitro – In vivo correlation (IVIVC); Drug release kinetics; Suppositories; Rectal drug delivery; Amoxicillin; Absolute bioavailability
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.09.015

In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro – in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility. [Display omitted] •Amoxicillin sodium (AS) existed in suppositories as a suspension.•The pharmacokinetic profiles were linked to the AS release mechanisms.•Slow release of AS from the PEG suppositories led to incomplete absorption.•AS in lipophilic suppositories was almost completely absorbed and well-tolerated.•AS up to 200 mg was rectally absorbed via non-saturated transport in rabbits.