VACUUM PACKAGING

IMPACT ON COLD-SENSITIVE DRUGS:

EXAMPLE OF 5-FLUOROURACIL

A.Cèbe1, G. Bouguéon1,2, M. Sangnier1, A. Khan1, J-M.

Bernadou1, P. Dufourcq3, S. Crauste-Manciet1,2
1Pharmaceutical Technology Department, Bordeaux University Hospital, France
2ARNA Laboratory ChemBioPharm U1212 INSERM - UMR 5320 CNRS, Bordeaux University,
France
3Biology of Cardiovascular Diseases, Inserm U1034, Pessac, France

22ème édition,
2/3/4 octobre 2019
OBJECTIVE
vacuum packaging of sterile injectable
preparations
► qualify the packaging method by
assessing physical stability of 5-
Fluorouracil (5-FU)

ensure
preservation preparations cooling
improvement
low-temperature stability ?
of anticipated
cytotoxic preparations crystallization ?

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MATERIALS AND METHODS
→ pack machine C200 MULTIVAC®, 2,3s at 4mBar
Validation of a semi-automatic vacuum pack machine for batch preparations, C. Dupire, G. Bouguéon, L. Sauvaget,
C. Gary, V. Servant, R. Legeron, A. Berroneau, D. Breilh, S. Crauste-Manciet

→ 50 mg/mL preparations (n=3)

→ Freeflex Fresenius® 50mL sodium chloride bags

→ MICROSCOPY OBSERVATION
Observer Z1, DIC x20, ZEISS
Before / after packaging n=9 / n=9
Negative control (NaCl) n=3
Positive (PC1 and PC2) controls n=3 / n=3

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MICROSCOPY OBSERVATION :
POSITIVE CONTROLS

vacuum filtration

PC2 PC1
(commercialized (obtained by
vial under cold submitting to a
storage) 4-5°C storage)

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 MICROSCOPY (DIC X20, ZEISS MICROSCOPY)

scale bar = 50µm

PC1 crystals : acicular structure, needles length between 50 to 100µm.

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 MICROSCOPY (DIC X20, ZEISS MICROSCOPY)

scale bar = 50µm

PC2 prismatic crystals with a 100 to 600µm length.

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 MICROSCOPY (DIC X20, ZEISS MICROSCOPY)

PC2 PC1

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 MICROSCOPY OBSERVATION :
NEGATIVE CONTROL

NaCl ambient temperature

frozen
NaCl

50µm

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MICROSCOPY (DIC X20, ZEISS MICROSCOPY) 50µm

After
MULTIVAC®

Before
MULTIVAC®

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MICROSCOPY (DIC X20, ZEISS MICROSCOPY) 50µm

After
MULTIVAC®

NaCl

Before
MULTIVAC®

no crystallization

10
50µm
DISCUSSION - CONCLUSION

➔ In our study conditions, we can safely conclude that vacuum

packaging will not affect the physical state of cold sensitive
drugs.

➔ This simple test could be suggested as process validation

method for cold sensitive drugs when vacuum conditions
(pressure or time) are modified.

➔ Physicochemical stability study need to be done

find a stability indicating method
HPLC-UV does not allow degradation products observation

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THANK YOU FOR
YOUR ATTENTION

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