Physical stability of an admixture for TPN
There are several options available for choosing parental emulsion. These include Omegaven containing highly refined fish oil, Lipidem containing ώ-3 acid triglyceride and SMOFlipid containing ώ-3 and ώ-6 fatty acids. The most suitable parental emulsion for this patient will be SMOFlipid as it contains both ώ-3 and ώ-6 (BNF 59, 2010). The lipid emulsion reduces the amount of ώ-6 FA and increases the level of ώ-3 FA which further results in a decreases the ratio to 2:5:1 for ώ-6: ώ-3. The final end product is acceptable as it matches with the current level of recommendations (Waterberg, 2005).
There are many factors that affect the stability of the admixture. One of the important factors includes globule size as it affects the stability and toxicity of the emulsion. The globules from size 0.5 to 1.0 µm are more rapidly consumed by the body as compared to the globule of size 3-5 µm. There is an increased occurrence of emboli which can lead to changed blood pressure if the globules are bigger than 4-6 µm. In order to attain an optimal stability the globule size must be minimized and size distribution should be controlled. It has been found that the emulsion with globule size of 200-500 nm has better physical stability (Floyd, 1999). Moreover the surface potential of emulsions that are lecithin stabilised have an important role in stabilizing emulsions that contain drug. This is done by electrostatic repulsion. Due to the delivery of neutral and ionised phospholipids that exist within lecithin, a surface charge (zeta potential) of -40 to - 50 mV is produced. The globule size, stability and plasma clearance can be positively affected by ionised lipids by increased surface charge and thickness of bilayer for phospholipids. Due to the decline in the electrical charge the flocculation rate and coalescence are increased. (Floyd, 1999). The rise in temperature can have a major impact on the solubility of some ions like Ca2+ as the dissociation of calcium is increased and can therefore also result in precipitation (Allwood et al, 1998). It has been also found that the higher temperature can cause coalescence to the total nutrition admixtures (Lee et al, 2003).
The stability of the admixture need to be properly assessed as there is a high risk of stability change involved due to the different number of excipient used. Instabilities can give rise to precipitation and coalescence. This can further aggravate affects like fat embolism syndrome within the patients (Lee et al, 2003).
There are various methods that can be used to assess the physical stability of the admixture. One of the ways is by assessing the globule size through various methods which include microscopy, electrical zone sensing and light scattering (laser diffraction and photon related spectroscopy). Moreover a new method which involves using the technique of optical sensing for single particle is used to find out the number of particles (Koster et al, 1996). Other methods involve examination with eye or electron microscopy to detect precipitation, flocculation or coalescence (Floyd, 1999). Furthermore the flocculation can be detected within the emulsion by microscopy or turbidimetry; however these processes are time consuming. Particle size analyser also known as Coulter Counter can be used to measure the coalescence (Washington, 1996).
There are other stability issues which need to be taken into account. Microbiological stability of the TNA should be considered as infusion that is diluted do not sustain same growth- promoting characteristics as emulsion that is undiluted and therefore might comprise of preservative. Every care should be taken to avoid microbiological contamination when making emulsions. The presence of glucose results in lower pH of the admixture therefore can further cause coalescence (Schroder, 2008). Furthermore the sunlight (UV light) can cause long-lasting damage to the admixture due to photolysis (Allwood, 1998). There can be a colour change in the admixture due to the photo oxidation of amino acids and therefore the end product can be very toxic (Allwood, 1996).
There are a number of elements which need to be considered during the handling and use of SMOFlipid. The emulsion should be used only if it is homogenous. The emulsion should be examined visually to detect if there is any separation within the phase before it is administrated. The emulsion should be used once only and the unused emulsion should be discarded once the bag is opened. Furthermore the shelf life is no more than 24 hours at the temperature of 2-8 oC (SPC, 2006). In order to avoid any vigorous shaking to the admixture precautions must be taken as oxidation of the emulsion can be caused (Lee et al, 2003).
References
· Allwood M C and Kearney M C J. (1998). Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition. 14 (9), 697-706.
This article was used within the text as it contained information about factor that affect the stability of the admixture.
* Allwood M C, Gil H, Sizer T, Driscoll D F. (1996). Effects of Air and Oxygen on parenteral nutrition admixtures-An underrated risk? , Nutrition. 12 (3), 222-223.
This article was used as it contained information about the other factor which may affect the stability of the admixture.
· British National Formulary 59 (2010),
The BNF was used to find out the list of different parenteral emulsions available currently.
· Floyd A G. (1999). Top ten considerations in the development of parenteral emulsions. Pharmaceutical science & technology today. 2 (4), 134-143.
This article was used as it contained good information about stability factors and methods available for testing particle size.
· Koster V S, Kuks P F M, Lange R, Talsma H. (1996). Particle size in parental fat emulsion, what are the true limitations? ; International Journal of Pharmaceutics. 134, 235-238
This article was used because it has a good insight about the different methods available for assessing stability of admixtures.
· Lee M D, Yoon J, Kim S, Kim I. (2003). Stability of total nutrient admixtures in reference to ambient temperatures. Nutrition. 19, 886-890.
This article was used as it has information about handling and use of SMOFlipid
· Schrøder A M. (2008). Total parenteral nutrition - Problems compatibility and stability. European journal of hospital pharmacist. 14, 65-67.
This article was used as it has the information about other factors that affect the stability of the admixture.
· Summary of product characteristics for SMOFlipid (2006), available at http://www2.fresenius-kabi.com/internet/kabi/gb/fkintpub.nsf/AttachmentsByTitle/SMOFlipid+SmPC/$FILE/SMOFlipid+SmPC.pdf (last accessed 27/03/10)
This website was used to assess the SPC for SMOFlipid as it had information about handling and use of the drug.
· Waitzberg D L. (2005). Evolution of parenteral lipid emulsion. Clinical Nutrition Supplements. 1, 5-7.
This article was used as it contained the information about SMOFlipid and excipient within it.
· Washington C. (1996). Stability of lipid emulsions for drug delivery. Advanced drug delivery reviews. 20, 131-145.
This article was used as he it contained the information about the different methods used to assess to stability.
