Quality assessment of total parenteral nutrition admixtures by the use of fractional factorial design

Abstract

Background/Aim. Parenteral nutrition as a specific aspect of providing nutritients still remains a permanent topic of both theoretical and experimental research. Total parenteral nutrition (TPN) admixtures have complex contents making difficult to maintain their stability. The most critical parameter is the diameter of a lipid droplet, i.e. droplet size distribution. It is recommended that droplet size should not be more than 5 ??m and that the presence of greater droplets should not exceede the value of 0.05%. Lipid droplets size is affected particularly by electrolyte addition, especially polyvalent cations. There is a danger of the added electrolytes interaction with lipid droplets which leads to their aggregation and negative effects upon the admixtures stability. The aim of this study was to assess the effect of added electrolyte and lipid phase quantity on the admixture stability. Methods. Electrolytes were added to the studied admixture of a defined basic formulation contents in accordance with recommendations from the literature. Droplets size measurements were performed using the method of laser diffraction with a laser particles analyzer. Effects of independent variables were calculated and evaluated using commercial software. Na+, K+, Ca2+ and Mg2+ concentrations, as well as the quantity of fat phase were chosen as studied factors, i.e. independed variables. The system response, or dependent variable was the median of droplets size. Each of the factors was varied at two levels, higher (+1) and lower (-1), according to the 25-2 fractional factorial design. Results. The study suggested the presence of relative uniformity of the results of all the measurements regardless of the quantity of added electrolytes and lipid phase. It was shown that undoubtedly there is the influence of 2- valent cations (calcium and magnesium) upon lipid droplets size, which is in a direct correlation with theoretical assumption. Conclusion. Within a 72-hour testing period there was no significant increase in droplet size, i.e. the studied admixtures remained stable considering droplet size median as the criterion of stability.Uvod/Cilj. Parenteralna ishrana, kao specifican vid nadoknade hranljivih materija, i dalje predstavlja stalnu temu teorijskog i eksperimentalnog izucavanja. Slozeni sastav smese za totalnu parenteralnu ishranu (TPI) otezava odrzanje njihove stabilnosti. Najkriticniji parameter je dijametar lipidnih kapi, odnosno raspodela velicina kapi. Postoji preporuka da velicina kapi ne bi trebalo da prelazi 5 ?m i da zastupljenost vecih kapi ne prelazi vrednost od 0,05%. Na velicinu lipidnih kapi poseban uticaj ima dodavanje elektrolita, narocito visevalentnih katjona. Postoji opasnost da dodati elektroliti interreaguju sa lipidnim kapima, sto dovodi do njihovog spajanja i ima negativan uticaj na stabilnost smesa. Cilj ovog rada bio je da se istrazi kako dodati elektroliti i kolicina lipidne faze uticu na stabilnost ovih smesa. Metode. Ispitivanoj smesi sa definisanim sastavom osnovne formulacije izradjenoj u bolnickoj apoteci, dodavani su elektroliti na osnovu preporuka iz literature. Merenje velicine kapi vrseno je metodom laserske difrakcije pomocu laserskog analizatora cestica. Uticaj nezavisno promenljivih je procenjen i izracunat primenom komercijalnog softvera. Kao nezavisno promenljive, u svojstvu ispitivanih faktora izabrani su koncentracije Na+, K+, Ca2+ i Mg2+, kao i kolicina masne faze. Odgovor sistema, ili zavisno promenljiva velicina, bila je medijana veli- cine kapi. Svaki od faktora variran je na dva nivoa, gornji (+1) i donji (-1), odnosno primenjen je 25-2 frakcioni faktorijalni dizajn. Rezultati. Istrazivanje je pokazalo da nezavisno od kolicine dodatih elektrolita i kolicine lipidne faze postoji relativna ujednacenost rezultata za sva merenja. Analiza pojedinacnih faktora ukazuje na nesumnjiv uticaj dvovalentnih katjona (kalcijuma i magnezijuma) na velicinu lipidnih kapi, sto je u direktnoj korelaciji sa teoretskim postavkama. Zakljucak: Tokom ispitivanog 72-casovnog perioda nije bilo znacajnog povecanja velicine kapi, odnosno ispitivana smesa ostala je stabilna sa stanovista medijane velicine kapi kao kriterijuma stabilnosti. PR Projekat Ministarstva nauke Republike Srbije, br. 41018