Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial
Introduction: The objectives of this study were to develop a stability-indicating high performance liquid chromatography (HPLC) assay for benzylpenicillin (BPC) in pharmaceutical fluids, and to investigate the stability of (i) isotonic citrate-buffered BPC solutions at the clinically relevant concen...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | http://hdl.handle.net/20.500.11937/88953 |
| _version_ | 1848765123218374656 |
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| author | Batty, Kevin Page-Sharp, Madhu Salman, S. Hla, T.K. Manning, L. |
| author_facet | Batty, Kevin Page-Sharp, Madhu Salman, S. Hla, T.K. Manning, L. |
| author_sort | Batty, Kevin |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Introduction: The objectives of this study were to develop a stability-indicating high performance liquid chromatography (HPLC) assay for benzylpenicillin (BPC) in pharmaceutical fluids, and to investigate the stability of (i) isotonic citrate-buffered BPC solutions at the clinically relevant concentration of 30 mg/mL, and (ii) low concentration citrate-buffered BPC intravenous infusions (5–30 μg/mL).
Methods: The stability of isotonic BPC solutions containing 3.4 or 7.2 mg/mL sodium citrate was compared against contemporary hypertonic solutions. The HPLC assay was shown to be stability-indicating following acidic, alkali, oxidative and elevated temperature stress testing.
Results: After 7 d storage at 4 °C and 24 h at 35 °C, the concentrations of isotonic BPC 30 mg/mL solutions containing 3.4 and 7.2 mg/mL sodium citrate were 96% and 95% respectively, compared to day 0. After 3 d at 4 °C and 24 h at room temperature (22 °C), the concentrations of isotonic BPC solutions with 3.4 and 7.2 mg/mL sodium citrate were 99% and 96% respectively, compared to day 0. These data were comparable to the hypertonic solutions and meet pharmacopeial stability requirements. Low concentration BPC infusions showed 0.5% and 2.5% degradation after 24 h storage at 22 °C and 35 °C, respectively.
Conclusions: The isotonic BPC 30 mg/mL formulation is simple to prepare and may offer clinical benefits in settings where hypertonic solutions are problematic. This study provides assurance that high- and low-dose isotonic BPC infusions are stable at room temperature and our findings may be applicable to in vitro studies of BPC. |
| first_indexed | 2025-11-14T11:30:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-88953 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:30:15Z |
| publishDate | 2022 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-889532022-08-05T07:26:56Z Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial Batty, Kevin Page-Sharp, Madhu Salman, S. Hla, T.K. Manning, L. Benzylpenicillin HPLC (High-performance liquid chromatography) Intravenous infusion Sodium citrate Stability Drug Stability Humans Hypertonic Solutions Infusions, Intravenous Isotonic Solutions Penicillin G Sodium Citrate Temperature Introduction: The objectives of this study were to develop a stability-indicating high performance liquid chromatography (HPLC) assay for benzylpenicillin (BPC) in pharmaceutical fluids, and to investigate the stability of (i) isotonic citrate-buffered BPC solutions at the clinically relevant concentration of 30 mg/mL, and (ii) low concentration citrate-buffered BPC intravenous infusions (5–30 μg/mL). Methods: The stability of isotonic BPC solutions containing 3.4 or 7.2 mg/mL sodium citrate was compared against contemporary hypertonic solutions. The HPLC assay was shown to be stability-indicating following acidic, alkali, oxidative and elevated temperature stress testing. Results: After 7 d storage at 4 °C and 24 h at 35 °C, the concentrations of isotonic BPC 30 mg/mL solutions containing 3.4 and 7.2 mg/mL sodium citrate were 96% and 95% respectively, compared to day 0. After 3 d at 4 °C and 24 h at room temperature (22 °C), the concentrations of isotonic BPC solutions with 3.4 and 7.2 mg/mL sodium citrate were 99% and 96% respectively, compared to day 0. These data were comparable to the hypertonic solutions and meet pharmacopeial stability requirements. Low concentration BPC infusions showed 0.5% and 2.5% degradation after 24 h storage at 22 °C and 35 °C, respectively. Conclusions: The isotonic BPC 30 mg/mL formulation is simple to prepare and may offer clinical benefits in settings where hypertonic solutions are problematic. This study provides assurance that high- and low-dose isotonic BPC infusions are stable at room temperature and our findings may be applicable to in vitro studies of BPC. 2022 Journal Article http://hdl.handle.net/20.500.11937/88953 10.1016/j.jiac.2022.04.016 eng restricted |
| spellingShingle | Benzylpenicillin HPLC (High-performance liquid chromatography) Intravenous infusion Sodium citrate Stability Drug Stability Humans Hypertonic Solutions Infusions, Intravenous Isotonic Solutions Penicillin G Sodium Citrate Temperature Batty, Kevin Page-Sharp, Madhu Salman, S. Hla, T.K. Manning, L. Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title | Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title_full | Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title_fullStr | Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title_full_unstemmed | Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title_short | Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| title_sort | stability of benzylpenicillin for continuous intravenous infusions: an isotonic formulation for therapeutic use and a low-dose formulation for clinical trial |
| topic | Benzylpenicillin HPLC (High-performance liquid chromatography) Intravenous infusion Sodium citrate Stability Drug Stability Humans Hypertonic Solutions Infusions, Intravenous Isotonic Solutions Penicillin G Sodium Citrate Temperature |
| url | http://hdl.handle.net/20.500.11937/88953 |