Sains Malaysiana 48(5)(2019): 1043–1054

http://dx.doi.org/10.17576/jsm-2019-4805-13

 

Superolein Based Intravenous Lipid Emulsion 20% w/w Physicochemical Characterization, Stability and Its Effect on Liver Status

(Superolein berasaskan Emulsi Lipid Intravena 20% w/w Pencirian Fizikokimia, Kestabilan dan Kesannya pada Keadaan Hati)

 

MOHD. HAZ HAIRUL AMRAN^1,2, MOHD. FAIRUZ DANIK¹, MOHD. SHAKRIE PALAN ABDULLAH^3,4, MOHD. HANIF ZULFAKAR¹ & AHMAD FUAD SHAMSUDDIN^1,5*

 

¹Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

²Parenteral Nutrition Unit, Department of Pharmacy, Hospital Kuala Lumpur, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

³Department of Pharmacy, Faculty of Medicine, 50603 Kuala Lumpur, Federal Territory, Malaysia

 

⁴Pharmacy Service Division - Enforcement Pharmacy, Kelantan State Health Department, Wisma Persekutuan Kota Bharu, Jalan Bayam, 15590 Kota Bharu, Kelantan, Malaysia

 

⁵Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine, 30450 Ipoh, Perak Darul Ridzuan, Malaysia

 

Diserahkan: 16 Oktober 2018/Diterima: 25 Mac 2019

 

ABSTRACT

Long chain triglycerides (LCT) from soya oil have been reported to cause hepatic abnormalities among patients receiving parenteral nutrition. A new source for LCT is needed to support current therapy. The aims of this study were to develop a good and stable superolein oil based intravenous lipid emulsion 20% (SoLE), and to determine its effect on liver status of an animal model. The emulsion was prepared using superolein oil and medium chain triglyceride oil (1:1), 1.2 g lecithin and homogenized by high pressure homogenization method. The physical stability study was performed based on real-time, accelerated, force degradation and environmental degradation. Chemical stability was measured based on fatty acids and vitamin E contents, peroxide value and acidity value. As the animal model, three rabbits were administered with 1.5 g/kg SoLE for 5 h and repeated daily for three days. The SoLE was found to have good physicochemical characters: 229.07±1.57 nm of particle size; 0.00% of particle > 5 μm; 342.00±1.00 mOsm/kg of osmolarity; -46.67±4.40 mV of zeta potential; 1.72±0.04 cP of viscosity; 7.83±0.06 of pH; 0.80±0.06 kcal/g calorie; 1.74±0.05 mEqO2/kg of peroxide value; and 0.03±0.01% of acidity value, and excellent physicochemical stabilities for up to six months of storage at various temperatures and conditions. The level of plasma lipid and plasma liver enzymes profiles of the rabbits remained statistically unchanged. This study has successfully developed a stable SoLE 20% and it was found to be safe to the liver of the animal model.

 

Keywords: Animal model; intravenous lipid emulsion; physicochemical; stability; superolein oil

 

ABSTRAK

Trigliserida rantaian panjang (LCT) daripada minyak kacang soya telah dilapor menyebabkan keabnormalan hepatik dalam kalangan pesakit yang menerima nutrisi parenteral. Sumber baharu untuk LCT diperlukan bagi menyokong terapi semasa. Tujuan kajian ini adalah untuk membangunkan emulsi lipid intravena 20% (SoLE) berasaskan minyak superolein yang baik dan stabil dan menentukan kesannya terhadap status hati model haiwan. Emulsi telah disediakan dengan menggunakan minyak superolein dan minyak trigliserida rantaian sederhana (1: 1), 1.2 g lesitin dan dihomogenkan dengan kaedah penghomogenan tekanan tinggi. Kajian kestabilan fizikal dijalankan berdasarkan masa sebenar, dipercepat, degradasi paksa dan degradasi persekitaran. Kestabilan kimia dihitung berdasarkan kandungan asid lemak, kandungan vitamin E, nilai peroksida dan nilai keasidan. Sebagai model haiwan, tiga ekor arnab diberikan 1.5 g/kg SoLE selama 5 jam dan diulang setiap hari selama tiga hari. SoLE didapati mempunyai sifat fizikokimia yang baik iaitu 229.07±1.57 nm saiz zarah, 0.00% zarah bersaiz melebihi 5 μm, 342.00±1.00 mOsm/kg osmolariti, -46.67±4.40 mV potensi zeta, 1.7 ±0.04 cP kelikatan, 7.83±0.06 pH, 0.80±0.06 kcal/g kalori, 1.74±0.05 mEqO2/kg nilai peroksida dan 0.03±0.01% nilai keasidan serta kestabilan fizikokimia pula adalah cemerlang sehingga enam bulan penyimpanan pada pelbagai suhu dan keadaan. Tahap profil lipid plasma dan enzim hati plasma haiwan yang dikaji kekal tidak berubah secara statistik. Kajian ini telah berjaya membangunkan SoLE 20% yang stabil dan selamat kepada hati model haiwan.

 

Kata kunci: Emulsi lipid intravena; kestabilan fizikokimia; minyak superolein; model haiwan

RUJUKAN

Abu-Fayyad, A. & Nazzal, S. 2017. Extraction of Vitamin E isomers from palm oil: Methodology, characterization and in vitro anti-tumor activity. Journal of America Oil Chemists’ Society 94(9): 1209-1217.

Alayoubi, A., Abu-Fayyad, A., Rawas-Qalaji, M.M., Slyvester, P.W. & Nazzal, S. 2015. Effect of lipid viscosity and lipid viscosity of ‘Vitamin E’ enriched emulsion. Pharmaceutical Development and Technology 20(5): 555-561.

Anez-Bustillos, L., Dao, D.T., Baker, M.A., Fell, G.L., Puder, M. & Gura, K.M. 2016. Intravenous fat emulsion formulations for the adults and pediatric patient: Understanding the differences. Nutritional in Clinical Practice 31(5): 596-609.

Arain, Q.S., Talpur, F.N., Channa, N.A., Ali, M.S. & Afridi, H.I. 2017. Serum lipid profile as a marker of liver impairment in hepatitis B cirrhosis patients. Lipids in Health and Disease 16(51). https://doi.org/10.1186/s12944-017-0437-2. Accessed on 8 January 2019.

Arrigo, T., Leonardi, S., Cuppari, C., Manti, S., Lanzafame, A., D’Angelo, G., Gitto, E., Marseglia, L. & Salpietro, C. 2015. Role of the diet as a link between oxidative stress and liver diseases. World Journal of Gastroenterology 21(2): 384-395.

Bajaj, S., Singla, D. & Sakhuja, N. 2012. Stability testing of pharmaceutical products. Journal of Applied Pharmaceutical Products 2(3): 129-138.

Berteau, C., Filipe-Santos, O., Wang, T., Rojas, H.E., Granger, C. & Schwarzenbach, F. 2015. Evolution of the impact of viscosity, injection volume and injection flow rate on subcutaneous injection tolerance. Medical Devices: Evidence and Research 8: 473-484.

Blessy, M., Patel, R.D., Prajapati, P.N. & Agrawal, Y.K. 2014. Development of forced degradation and stability indicating studies of drugs - A review. Journal of Pharmaceutical Analysis 4(3): 159-165.

Cheong, A.M. & Nyam, K.L. 2016. Improvement of physical stability of kenaf seed oil-in-water nanoemulsions by addition of β-cyclodextrin to primary emulsion containing sodium caseinate and Tween 20. Journal of Food Engineering 183: 24-31.

Derawi, D., Abdullah, B.M., Zaman Huri, H., Yusop, R.M., Salimon, J., Hairunisa, N. & Salih, N. 2014. Palm olein as renewable raw materials for industrial and pharmaceutical products applications: Chemical characterization and physicochemical properties studies. Advances in Materials Science and Engineering 2014: 134063

Driscoll, D.F. 2017. Pharmaceutical and clinical aspects of lipid injectable emulsions. Journal of Parenteral and Enteral Nutrition 41(1): 1-10.

Driscoll, D.F. 2015. Commercial lipid emulsions and all-in-one mixtures for intravenous infusion-composition and physicochemical properties. World Review of Nutrition and Dietetics 112: 48-56.

Driscoll, D.F. 2007. Globule-size distribution in injectable 20% lipid emulsions: Compliance with USP requirement. American Journal of Health-System Pharmacists 64: 2032- 2036.

Driscoll, D.F. 2006. Lipid injectable emulsions: Pharmacopeial and safety issues. Pharmaceutical Research 23(9): 1959- 1969.

Eriksson, L. 2016. Method development and optimization for determination of lipid oxidation in emulsions. Tesis M.Sc., Teknisk-naturvetenskaplig fakultet, Uppsala Universitet (Unpublished).

Fell, G.L., Nandivada, P., Gura, K.M. & Puder, M. 2015. Intravenous lipid emulsions in parenteral nutrition. Advances in Nutrition 6: 600-610.

Gharby, S., Harhar, H., Boulbaroud, S., Bouzoubaa, Z., el Madani, N., Chafchaouni, I. & Charrouf, Z. 2014. The stability of vegetable oils (sunflower, rapeseed and palm) sold on the Moroccan market at high temperature. International Journal of Chemical and Biochemical Sciences 5: 47-54.

Gornas, P. & Siger, A. 2015. Simplified sample preparation and rapid detection by RP-HPLC/FLD of tocopherols and tocotrienols in margerines: Preliminary screening of plant fats-potential quality markers. European Journal of Lipid Science and Technology 117: 1589-1597.

Ismail, A., Bannenberg, G., Rice, H.B., Schutt, E. & MacKay, D. 2016. Oxidation in EPA- and DHA-rich oils: An overview. Lipid Technology 28(3-4): 55-59.

Jufri, M., Azmi, N. & Shamsuddin, A.F. 2012. Effects of intravenous palm oil-based lipid nanoemulsion on fat metabolism in rabbits. Asian Pacific Journal of Tropical Disease 2(Supp. 2): S944-S948.

Kang, S.W., Kim, H.M., Rahman, M.S., Kim, A.N., Yang, H.S. & Choi, S.G. 2017. Nutritional quality and physicochemical characteristics of defatted bovine liver treated by supercritical carbon dioxide and organic solvent. Korean Journal for Food Science of Animal Resources 37(1): 29-37.

Kaur, K., Kumar, R., Arpita, G.S., Uppal, S., Bhatia, A. & Mehta, S.K. 2017. Physicochemical and cytotoxicity study of TPGS stabilized nanoemulsion designed by ultrasonication method. Ultrasonics Sonochemistry 34: 173-182.

Khanum, R. & Thevanayagam, H. 2017. Lipid peroxidation: Its effects on the formulation and use of pharmaceutical emulsions. Asian Journal of Pharmaceutical Sciences 12(5): 401-411.

Kuchler, S., Schneider, C., Lerche, D. & Sobisch, T. 2006. Process optimisation for making stable emulsions using accelerated dispersion analysis by multisample analytical centrifugation. https://www.researchgate.net/publication/266686735. Accessed on 11 March 2018).

Lampi, A.M. 2011. Analysis of tocopherols and tocotrienols by HPLC. AOCS Lipid Library. http://www.lipidlibrary.aocs. org/Analysis/content.cfm?ItemNumber=40389. Accessed on 8 March 2018.

Magosso, E., Ansari, M.A., Gopalan, Y., Shuaib, I.L., Wong, J.W., Khan, N.A., Abu Bakar, M.R., Ng, B.H. & Yuen, H.H. 2013. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: A randomised placebo-controlled clinical trial. Nutrition Journal 12: 166-173.

Malakouti, M., Kataria, A., Ali, S.K. & Schenker, S. 2017. Elevated liver enzymes in asymptomatic patients-what should I do? Journal of Clinical and Translational Hepatology 5(4): 394-403.

Manzanares, W., Dhaliwal, R., Jurewitsch, B., Stapleton, R.D., Jeejeebhoy, K.N. & Heyland, D.K. 2013. Alternative lipid emulsions in the critically ill: A systematic review of the evidence. Intensive Care Medicine 39(10): 1683-1694.

Mayada, R.F., Taghred, M.S. & Haytham, A.A. 2015. Boldenone-induced apoptotic, structural and functional alterations in the liver of rabbits. World Rabbit Science 23: 39-46.

Mba, O.I., Dumont, M.J. & Ngadi, M. 2015. Palm oil: Processing, characterization and utilization in the food industry - A review. Food Bioscience 10: 26-41.

Meredith, A. & Rayment, L. 2000. Liver disease in rabbits. Seminars in Avian and Exotic Pet Medicine 9(3): 146-152.

Mourtas, S., Michanetzis, G.P., Missirlis, Y.F. & Antimisiaris, S.G. 2009. Haemolytic activity of liposomes: Effect of vesicle size, lipid concentration and polyethylene glycol-lipid or arsonolipid incorporation. Journal of Biomedical Nanotechnology 5: 1-7.

Mulet-Cabero, A.I., Rigby, N.M., Brodkorb, A. & Mackie, A.R. 2017. Dairy food structures influence the rates of nutrients digestion through different in vitro gastric behaviour. Food Hydrocolloids 67: 63-73.

Muller, R.H., Harden, D. & Keck, C.M. 2012. Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery. Drug Development and Industrial Pharmacy 38(4): 420-430.

Narang, D., Sood, S., Thomas, M.K., Dinda, A.K. & Maulik, S.K. 2004. Effect of dietary palm olein oil on oxidative stress associated with ischemic-reperfusion injury in isolated rat heart. BMC Pharmacology 4: 29. doi: 10.1186/1471-2210- 4-29.

Ng, H.N., Woi, P.M., Basri, M. & Ismail, Z. 2013. Characterization of structural stability of palm oil esters-based nanocosmeceuticals loaded with tocotrienol. Journal of Nanobiotechnology 11: 27.

Ng, M.H. & Choo, Y.M. 2012. Chromatographic analyses of tocopherols and tocotrienols in palm oil. Journal of Chromatographic Science 50: 283-286.

Ng, M.H., Abdul Gapor, M.T., Choo, Y.M. & Ma, A.N. 2006. Palm tocols (tocopherols and tocotrienols) as standard reference materials (MRM 3). MPOB Information Series ISSN 1511-7871 (MPOB TT No. 339).

Onyesom, I. & Anosike, E.O. 2007. Changes in rabbit liver function markers after chronic exposure to ethanol. Journal of Biochemistry, Molecular Biology, and Biophysics 2(5): 337-342.

Ozkan, C., Kaya, A. & Akgul, Y. 2012. Normal values of haematological and some biochemical parameters in serum and urine of New Zealand white rabbits. World Rabbit Science 20: 253-259.

Pasifico, S., Scognamiglio, M., D’Abrosca, B., Monaco, P. & Fiorentino, A. 2012. Tocopherols, tocotrienols and their biological analogs. In Handbook of Analysis of Active Compounds in Functional Foods, edited by Nollet, L.M.L. & Toldra, F. Boca Raton: CRC Press.

Raman, M., Almutairdi, A., Mulesa, L., Alberda, C., Beattie, C. & GramLich, L. 2017. Parenteral nutrition and lipids. Nutrients 9(388): 1-11.

RamLi, M.R., Siew, W.L. & Cheah, K.Y. 2009. Production of high oleic palm oils on a pilot scale. Journal of the American Oil Chemists’ Society 86: 587-594.

Ren, T., Cong, L., Wang, Y., Tang, Y., Tian, B., Lin, X., Zhang, Y. & Tang, X. 2013. Lipid emulsions in parenteral nutrition: Current applications and future developments. Expert Opinion on Drug Delivery 10(11): 1533-1549.

Roche, L.D., Medina, E.A., Perez, A.F., Viart, M.A.B., Lopez, Y.S., Cama, V.F., Lopez, A.M.V., Martinez-Sanchez, G. & Fernandez-Sanchez, E. 2012a. Lipofundin induced hyperlipidemia promotes oxidative stress and atherosclerotic lesions in New Zealand white rabbits. International Journal of Vascular Medicine 2012: 898769.

Roche, L.D., Perez, A.F., Viart, M.A.B. & Lopez, A.M.V. 2012b. Lipofundin 20% induces hepatic lipid peroxidation in New Zealand white rabbits. Revista MVZ Cordoba 17(3): 3113- 3117.

Sarwar, A., Vunguturi, S. & Ferdose, A. 2016. A study on smoke point and peroxide values of different widely used edible oils. International Journal of Engineering Technology Science and Research 3(5): 271-273.

Shahid, U., Ahmed Khan, D., Noor, U. & Ahmed Butt, S. 2012. Effect of tocotrienols on lipid profile in rabbits. Journal of Rawalpindi Medical College 16(1): 68-69.

Shousha, S.M., Mahmoud, M.A. & Hameed, K. 2017. Some haemato-biochemical value in white New Zealand rabbits. IOSR Journal of Agriculture and Veterinary Science 10(7): 40-44.

Staven, V., Wang, S., Gronlie, I. & Tho, I. 2016. Development and evalution of a test program for Y-site compatibility testing of total perenteral nutrition and intravenous drugs. Nutrition Journal 15: 29.

Sun, H., Yang, R., Wang, J., Yang, X., Tu, J., Xie, L., Li, C., Lao, Q. & Sun, C. 2017. Component-based biocompatibility and safety evaluation of polysorbate 80. RSC Advances 7: 15127-15138.

Tadros, T.F. 2013. Emulsion formation, stability and rheology. In Emulsion Formation and Stability, edited by Tadros, T.F. 1st Ed. Weinheim: Wiley.

Tan, S.K., Masoumi, H.R.F., Karjiban, R.A., Stanslas, J., Kirby, B.P., Basri, M. & Basri, H. 2016. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability. Ultrasonics Sonochemistry 29: 299-308.

Vanek, V.W., Seidner, D.L., Bistrian, B., Gura, K., Valentine, C.J., Novel Nutrient Task Force, Intravenous Fat Emulsions Workgroup & American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors. 2012. ASPEN Position Paper: Clinical role for alternative intravenous fat emulsions. Nutrition in Clinical Practice 27(2): 150-192.

Yadav, R.K., Singh, M., Roy, S., Ansari, M.N., Saeedan, A.S. & Kaithwasa, G. 2018. Modulation of oxidative stress response by flaxseed oil: Role of lipid peroxidation and underlying mechanisms. Prostaglandins and Other Lipid Mediators 135: 21-26.

Zainol, S., Basri, M., Basri, H., Shamsuddin, A.F., Abdul- Ghani, S.S., Abedi-Karjiban, R. & Abdul-Malek, E. 2012. Formulation optimization of a palm-based nanoemulsion system containing levodopa. International Journal of Molecular Sciences 13: 13049-13064.

Zhu, X., Xiao, Z., Xu, Y., Zhao, X., Cheng, P., Cui, N., Cui, M., Li, J. & Zhu, X. 2016. Differential impacts of soybean and fish oils on hepatocyte lipid droplet accumulation and endoplasmic reticulum stress in primary rabbit hepatocytes. Gastroenterology Research and Practice 2016: 9717014.

 

*Pengarang untuk surat-menyurat; email: fuad.shamsuddin@unikl.edu.my