The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis
Abstract
:1. Introduction
2. Results
2.1. Validation Variables for the HPLC-UV Method
2.2. The Forced Degradation Study
2.3. The Stability Study
2.4. Drug Solution Flow Rates and Viscosity
3. Discussion
4. Materials and Methods
4.1. Chemicals, Reagents and Diluents
4.2. Preparation of Solutions and the In Vitro Infusion Set-Up
4.3. The 24-H Stability Study
4.3.1. Chromatographic Apparatus and Conditions
4.3.2. The HPLC-UV Forced Degradation Study
4.3.3. Validation of the HPLC-UV Stability-Indicating Method
4.3.4. Measurements of pH and Osmolality
4.3.5. Visual Assessment
4.3.6. Particle Counts
4.4. Viscosity Measurements
4.5. Expression of the Results
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Validation Variables | Piperacillin (Mylan, Fresenius Kabi) | Tazobactam (Mylan, Fresenius Kabi) | Piperacillin (Pfizer) | Tazobactam (Pfizer) | |
---|---|---|---|---|---|
Calibration range | 150–350 µg/mL | 18.75–43.75 µg/mL | 150–350 µg/mL | 18.75–43.75 µg/mL | |
Determination coefficient | 0.997 | 0.999 | 0.999 | 0.996 | |
Regression coefficients | Slope | 867.85 | 4897.28 | 842.07 | 4763.45 |
Intercept | 7535.48 | 1247.50 | 3264.58 | 3560.96 | |
Limit of detection (µg/mL) | 8.227 | 0.576 | 4.488 | 1.279 | |
Limit of quantification (µg/mL) | 16.454 | 1.152 | 8.976 | 2.558 | |
Cochran’s test | Experimental value | 0.3966 | 0.334 | 0.4067 | 0.3155 |
Theoretical value (α = 5%; 5; 8) | 0.4564 | 0.4564 | 0.4564 | 0.4564 | |
ANOVA (non-linearity) | Experimental value (α = 5%; 1; 3) | 13,310.91 | 43,118.28 | 43,334.05 | 8284.46 |
Theoretical value | 4.11 | 4.11 | 4.11 | 4.11 |
Generic P/T (Fresenius Kabi) | T0 h (Bag Preparation) | T0 h | T8 h | T24 h |
---|---|---|---|---|
Appearance of the solution | Clear and colorless | Clear and colorless | Clear and colorless | Clear and colorless |
P concentration% | / | 100.0 ± 2.27 | 99.08 ± 0.64 | 97.91 ± 1.44 |
T concentration% | / | 100.0 ± 9.62 | 98.64 ± 7.79 | 97.39 ± 6.13 |
pH | 5.4 ± 0.0 | 5.3 ± 0.1 | 5.1 ± 0.1 | 5.0 ± 0.0 |
Osmolality (mOsm/kg) | 417 ± 4 | 417 ± 4 | 415 ± 3 | 418 ± 2 |
Particles ≥ 10 µm/mL | 396 ± 103 | 5 ± 4 | 2 ± 1 | 5 ± 4 |
Particles ≥ 25 µm/mL | 3 ± 2 | 0 ± 0 | 0 ± 1 | 0 ± 0 |
Generic P/T (Mylan) | T0 h (Bag Preparation) | T0 h | T8 h | T24 h |
---|---|---|---|---|
Appearance of the solution | Clear and colorless | Clear and colorless | Clear and colorless | Clear and colorless |
P concentration% | / | 100.0 ± 1.17 | 98.36 ± 0.70 | 95.40 ± 1.16 |
T concentration% | / | 100.0 ± 1.47 | 98.76 ± 0.80 | 99.88 ± 1.94 |
pH | 5.4 ± 0.0 | 5.4 ± 0.0 | 5.2 ± 0.1 | 4.9 ± 0.0 |
Osmolality (mOsm/kg) | 414 ± 3 | 415 ± 2 | 416 ± 3 | 415 ± 1 |
Particles ≥ 10 (µm/mL) | 31 ± 12 | 3 ± 3 | 2 ± 2 | 6 ± 3 |
Particles ≥ 25 (µm/mL) | 1 ± 1 | 0 ± 1 | 0 ± 0 | 1 ± 1 |
Proprietary Drug (Pfizer) | T0 h (Bag Preparation) | T0 h | T8 h | T24 h |
---|---|---|---|---|
Appearance of the solution | Clear and colorless | Clear and colorless | Clear and colorless | Clear and colorless |
P concentration% | / | 100.0 ± 1.04 | 97.06 ± 1.18 | 96.04 ± 0.87 |
T concentration% | / | 100.0 ± 3.45 | 103.01 ± 0.68 | 99.38 ± 0.16 |
pH | 6.1 ± 0.0 | 6.1 ± 0.0 | 6.0 ± 0.0 | 5.8 ± 0.0 |
Osmolality (mOsm/kg) | 439 ± 3 | 442 ± 1 | 442 ± 4 | 441 ± 4 |
Particles ≥ 10 (µm/mL) | 90 ± 8 | 7 ± 5 | 3 ± 1 | 5 ± 1 |
Particles ≥ 25 (µm/mL) | 1 ± 1 | 1 ± 1 | 0 ± 0 | 0 ± 1 |
Generic P/T (Mylan) in the Elastomeric Device | Generic P/T (Fresenius Kabi) in the Elastomeric Device | Proprietary Drug (Pfizer) in the Elastomeric Device | |
---|---|---|---|
Weight of the empty Folfusor® LV10 (g) | 62.04 ± 0.35 | 61.94 ± 0.30 | 61.76 ± 0.73 |
Weight of the filled Folfusor® LV10, before infusion (g) | 307.58 ± 0.61 | 305.30 ± 0.78 | 308.27 ± 1.28 |
Calculated weight of solution before infusion (g) | 245.55 ± 0.95 | 243.36 ± 0.48 | 246.52 ± 1.72 |
Calculated volume of solution before infusion (mL) | 239.09 ± 0.92 | 236.96 ± 0.46 | 239.34 ± 1.67 |
Calculated weight of solution after the 24-h infusion (g) | 20.02 ± 3.60 | 20.29 ± 4.59 | 24.84 ± 5.01 |
Calculated volume of solution after the 24-h infusion (mL) | 19.50 ± 3.50 | 19.76 ± 5.47 | 24.12 ± 4.86 |
Proportion of infusion solution not infused (volume, %) | 8.12 ± 1.46 | 8.23 ± 1.86 | 10.04 ± 2.03 |
Analysis Time (min) | Organic Phase/Aqueous Phase % |
---|---|
0–3 | 0/100 |
3.5–11 | 8/92 |
11.5–20 | 30/70 |
20.5–25 | 0/100 |
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Négrier, L.; Mena, A.M.; Dupont, C.; Gamache, P.; Zimbril, J.-O.; Abdoune, Y.; Karrout, Y.; Odou, P.; Genay, S.; Décaudin, B. The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis. Pharmaceuticals 2024, 17, 1085. https://doi.org/10.3390/ph17081085
Négrier L, Mena AM, Dupont C, Gamache P, Zimbril J-O, Abdoune Y, Karrout Y, Odou P, Genay S, Décaudin B. The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis. Pharmaceuticals. 2024; 17(8):1085. https://doi.org/10.3390/ph17081085
Chicago/Turabian StyleNégrier, Laura, Anthony Martin Mena, Christian Dupont, Philémon Gamache, Jeanne-Olive Zimbril, Yasmine Abdoune, Youness Karrout, Pascal Odou, Stéphanie Genay, and Bertrand Décaudin. 2024. "The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis" Pharmaceuticals 17, no. 8: 1085. https://doi.org/10.3390/ph17081085