Physical stability of a vitamin-lipid injectable emulsion

Introduction

The hospital pharmacy wants to centralize the production, in isolator, of vitamin-lipid syringes for neonatology service. The mixture is composed of: Smoflipid®20% (20 mL), Vitalipid®10% (8mL) and Soluvit® (2.4 mL). The emulsion is packaged in opaque syringes of 60 mL.

The purpose of the experiment is to carry out a study of physical stability over time.

Materials and methods

In the absence of chemical stability of the mixture an expiry period of 4 days has been fixed to cover the weekend productions. The study was carried out over 7 days, the syringes kept between 2-8 ° c. On day 3, a syringe was returned to room temperature for 24 hours to reproduce the infusion time. Tests were performed at D0, D1, D2, D3 + 24H, D4 and D7.

The different experiments carried out are: macroscopic analysis (n=1); pH measurement (n=1), potential zeta measurement (n=1), fat globules size measuring (n=3), osmolarity measurement (n=1).

For this study, a pHmeter, an osmometer and ZETA sizer nano were used.

Results and discussion

The macroscopic analysis reveals that there is no sign of creaming, sedimentation and phase separation.

The pH does not change: he is between 6.83-7.21. The solution becomes slightly acidic after 24h at room temperature. The pH should be as neutral as possible.

There is no variation on osmolality (389-420 mmol/kg).

The zeta potential is between -28 mV and -23 mV. Normal values are -20mV et-30 mV (1).

The size of lipid globule is between 302 nm and 323 nm during the seven days. The size of globules should not exceed 5 µm to prevent any risk of embolism

Conclusion

With all these parameters, the mixture has been stable for seven days. To complete the implementation of lipid syringe production, sterility testing and endotoxin testing were performed, as well as an aseptic filling test to validate the production process

(1) theses : Stabilité galénique de 8 mélanges nutritifs ternaires destinés à la nutrition parentérale pédiatrique — par Claire Ligier ; Critères de stabilité des mélanges de nutrition parentérale pédiatrique — Wilhelmine Mourier

(2) Globule-size distribution in injectable 20% lipid emulsions: compliance with USP requirements, David Driscoll