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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...

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Autores principales: Purohit, Trusha J., Amirapu, Satya, Wu, Zimei, Hanning, Sara M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383505/
https://www.ncbi.nlm.nih.gov/pubmed/37514051
http://dx.doi.org/10.3390/pharmaceutics15071865
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author Purohit, Trusha J.
Amirapu, Satya
Wu, Zimei
Hanning, Sara M.
author_facet Purohit, Trusha J.
Amirapu, Satya
Wu, Zimei
Hanning, Sara M.
author_sort Purohit, Trusha J.
collection PubMed
description 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.
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spelling pubmed-103835052023-07-30 Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin Purohit, Trusha J. Amirapu, Satya Wu, Zimei Hanning, Sara M. Pharmaceutics Article 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. MDPI 2023-07-01 /pmc/articles/PMC10383505/ /pubmed/37514051 http://dx.doi.org/10.3390/pharmaceutics15071865 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Purohit, Trusha J.
Amirapu, Satya
Wu, Zimei
Hanning, Sara M.
Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title_full Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title_fullStr Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title_full_unstemmed Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title_short Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin
title_sort rectal bioavailability of amoxicillin from hollow-type suppositories: effect of chemical form of amoxicillin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383505/
https://www.ncbi.nlm.nih.gov/pubmed/37514051
http://dx.doi.org/10.3390/pharmaceutics15071865
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