Results from the investigation of possible precipitation and emulsion stability following the mixing of drug and total parenteral nutrition (TPN) (n ≥3), V.W. MDD (volume weighted mean droplet diameter) and % size fractions: n=1 with multiple runs. Mix ratios denotes drug + TPNaq or drug + TPN, respectively. Shaded areas highlight values that might indicate an incompatible mix
Drug | Mix ratio Drug+TPN/TPNaq | Investigation of possible formation of precipitation with TPNaq | Testing of emulsion stability with TPN | ||||||||||||||
*Particles/ml ≥0.5 µm | Turbidity (FNU) | Visible particles and/or Tyndall effect (+/−) | pH | Light obscuration | Laser diffraction | pH | |||||||||||
PFAT5 | % <500 nm | % < 1 µm | V.W. MDD | ||||||||||||||
0h | 4h | 0h | 4h | 0h | 4h | 24 hours | 0h | 4h | 0h | 4h | 4h | 4h | 4h | 0h | 4h | ||
Baseline (TPNaq/TPN) | – | 17±15 | 136±40 | 0.32±0.17 | 0.86±0.50 | +/− | +/− | − | 5.89 | 5.89 | 0.11±0.01 | 0.18±0.02 | 82 | 100 | 375 | 5.89 | 5.89 |
Ampicillin 50 mg/mL† | 1+10 | 336±219 | 113±98 | 0.28±0.04 | 0.23±0.06 | + | + | + | 6.91 | 6.81 | 0.07±0.00 | 0.10±0.01 | 82 | 100 | 374 | 6.92 | 6.77 |
1+1 | 100±36 | 1932±200 | 0.45±0.17 | 0.67±0.06 | + | + | + | 7.95 | 7.92 | 0.08±0.01 | 0.04±0.01 | 83 | 100 | 373 | 8.03 | 7.92 | |
2+1 | 86±4 | 2287±591 | 0.96±0.10 | 1.03±0.16 | + | + | + | 8.16 | 8.19 | 0.07±0.00 | 0.04±0.01 | 85 | 100 | 370 | 8.23 | 8.16 | |
Ceftazidime 40 mg/mL‡ | 1+10 | 55±16 | 12±6 | 0.10±0.02 | 0.20±0.02 | − | − | + | 6.04 | 6.00 | 0.09±0.01 | 0.23±0.02 | 83 | 100 | 369 | 6.00 | 6.04 |
1+1 | 19±5 | 18±2 | 0.12±0.02 | 0.12±0.03 | − | − | − | 6.48 | 6.42 | 0.12±0.07 | 0.04±0.03 | 87 | 100 | 360 | 6.63 | 6.71 | |
1+2 | 27±12 | 13±6 | 0.10±0.01 | 0.10±0.01 | − | − | +/− | 6.33 | 6.28 | 0.09±0.02 | 0.14±0.02 | 83 | 100 | 370 | 6.36 | 6.45 | |
Fluconazole 2 mg/mL§ | 1+10 | 381±190 | 180±12 | 0.16±0.04 | 0.12±0.01 | + | +/− | − | 5.85 | 5.86 | 0.14±0.02 | 0.30±0.06 | 82 | 100 | 378 | 5.84 | 5.85 |
1+1 | 360±165 | 85±19 | 0.14±0.02 | 0.09±0.00 | + | +/− | − | 5.86 | 5.87 | 0.12±0.01 | 0.29±0.04 | 81 | 100 | 382 | 5.85 | 5.89 | |
9+1 | 92±4 | 77±26 | 0.08±0.02 | 0.07±0.01 | − | − | − | 5.85 | 5.87 | 0.10±0.01 | 0.32±0.28 | 80 | 100 | 385 | 5.88 | 5.90 | |
Fosphenytoin 10 mg/mL‡ | 1+50 | 135±19 | 33±4 | 0.10±0.01 | 0.10±0.01 | − | − | − | 5.94 | 5.96 | 0.11±0.01 | 0.15±0.04 | 82 | 100 | 374 | 5.91 | 5.92 |
1+1 | 132±14 | 27±10 | 0.09±0.02 | 0.18±0.08 | +/− | +/− | + | 7.47 | 7.44 | 0.09±0.00 | 0.04±0.00 | 83 | 100 | 375 | 7.34 | 7.23 | |
5+1 | 54±20 | 52±25 | 0.08±0.01 | 0.11±0.01 | − | − | − | 8.21 | 8.25 | 0.09±0.01 | 0.08±0.01 | 82 | 100 | 378 | 8.14 | 8.07 | |
Furosemide 2 mg/mL† | 1+100 | 436±215 | 105±31 | 0.14±0.05 | 0.10±0.01 | − | − | − | 5.87 | 5.90 | 0.13±0.03 | 0.24±0.02 | 83 | 100 | 373 | 5.84 | 5.85 |
1+1 | 561±319 | 39±16 | 0.13±0.04 | 0.08±0.00 | +/− | +/− | +/− | 5.94 | 5.98 | 0.10±0.01 | 0.04±0.01 | 83 | 100 | 372 | 5.90 | 5.93 | |
2+1 | 518±284 | 51±26 | 0.12±0.02 | 0.09±0.01 | +/− | +/− | +/− | 5.99 | 6.02 | 0.09±0.01 | 0.04±0.02 | 83 | 100 | 374 | 5.97 | 5.98 | |
Metronidazole 5 mg/mL§ | 1+10 | 312±82 | 218±26 | 0.26±0.14 | 0.27±0.16 | +/− | +/− | − | 5.84 | 5.85 | 0.17±0.03 | 0.35±0.08 | 82 | 100 | 374 | 5.81 | 5.83 |
1+1 | 302±81 | 118±28 | 0.18±0.09 | 0.10±0.02 | +/− | − | − | 5.63 | 5.65 | 0.16±0.01 | 0.29±0.05 | 82 | 100 | 377 | 5.60 | 5.62 | |
5+1 | 252±25 | 109±85 | 0.10±0.01 | 0.10±0.01 | − | − | − | 5.29 | 5.28 | 0.15±0.05 | 0.27±0.10 | 82 | 100 | 377 | 5.27 | 5.29 | |
Paracetamol¶ 10 mg/mL§ | 1+10 | 40±1 | 42±9 | 0.14±0.01 | 0.13±0.02 | − | − | − | 5.70 | 5.71 | 0.08±0.00 | 0.20±0.01 | 80 | 100 | 379 | 5.75 | 5.76 |
1+1 | 13±1 | 12±4 | 0.35±0.01 | 0.36±0.02 | + | + | + | 5.30 | 5.31 | 0.09±0.01 | 0.15±0.01 | 83 | 100 | 374 | 5.33 | 5.33 | |
1+2 | 25±6 | 28±12 | 0.26±0.01 | 0.26±0.01 | + | + | + | 5.39 | 5.38 | 0.12±0.02 | 0.36±0.15 | 83 | 100 | 374 | 5.40 | 5.42 |
*Particle counts above 10 and 25 µm are not shown as the Ph.Eur. limits were not exceeded in any of the samples.
†Diluted in 9 mg/mL NaCl.
‡Diluted in 50 mg/mL glucose.
§Undiluted.
¶All tests were performed with paracetamol from B. Braun, except for laser diffraction measurements where the paracetamol was from Fresenius Kabi.