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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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1865 |
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| author | Trusha J. Purohit Satya Amirapu Zimei Wu Sara M. Hanning |
| author_facet | Trusha J. Purohit Satya Amirapu Zimei Wu Sara M. Hanning |
| author_sort | Trusha J. Purohit |
| collection | DOAJ |
| 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; <i>p</i> = 0.9682). Both HTS formulations showed little or no irritation to the rectal mucosa following a single dose. |
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| format | Article |
| id | doaj.art-0918d4d47caf454980885a3a946bc52e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:43:33Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0918d4d47caf454980885a3a946bc52e2023-11-18T20:54:56ZengMDPI AGPharmaceutics1999-49232023-07-01157186510.3390/pharmaceutics15071865Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of AmoxicillinTrusha J. Purohit0Satya Amirapu1Zimei Wu2Sara M. Hanning3School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandDepartment of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandSchool of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandSchool of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandRectal 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; <i>p</i> = 0.9682). Both HTS formulations showed little or no irritation to the rectal mucosa following a single dose.https://www.mdpi.com/1999-4923/15/7/1865hollow-type suppositoriesamoxicillinrectal drug deliverybioavailabilitytissue tolerancestability |
| spellingShingle | Trusha J. Purohit Satya Amirapu Zimei Wu Sara M. Hanning Rectal Bioavailability of Amoxicillin from Hollow-Type Suppositories: Effect of Chemical Form of Amoxicillin Pharmaceutics hollow-type suppositories amoxicillin rectal drug delivery bioavailability tissue tolerance stability |
| 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 | hollow-type suppositories amoxicillin rectal drug delivery bioavailability tissue tolerance stability |
| url | https://www.mdpi.com/1999-4923/15/7/1865 |
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