Water-in-oil-in-water multiple emulsions of ibuprofen for paediatrics using african walnut seed oil

Main Article Content

Omotola Deborah Ogundipe Francis Abiodun Oladimeji


Multiple emulsions (MEs) have been used to prolong drug release from formulations. Hence, this study formulated water-in-oil-in-water (w/o/w) MEs of ibuprofen using African walnut seed oil (AWSO) for paediatrics use. The MEs were prepared by a two-step emulsification method, using Span 80® and Tween 80® as primary and secondary emulsifiers, respectively. The physical properties, drug entrapment efficiency, stability and drug release profile of the MEs were determined. From the study, stable MEs of ibuprofen (100 mg / 5 ml) can be prepared with 25 % w/v Span 80® as the primary emulsifier, and 8, 10 or 12 % w/v Tween 80® as the secondary emulsifier. The optimum ratios of oil to water in the primary emulsion were 1:1 and 3:2, while that of primary emulsion to external aqueous phase were 1:1 and 1:2. The release of ibuprofen from the MEs was ≤ 35.6 % at 5 hours. The study offers ibuprofen emulsions which may require once daily dosing compared to other available paediatric dosage forms of the drug which require three to four times dosing daily. It also provides information on AWSO as a possible drug carrier in the formulation of w/o/w MEs of ibuprofen for paediatrics.

Article Details

How to Cite
OGUNDIPE, Omotola Deborah; OLADIMEJI, Francis Abiodun. Water-in-oil-in-water multiple emulsions of ibuprofen for paediatrics using african walnut seed oil. Journal of Applied Pharmaceutical Research, [S.l.], v. 7, n. 1, p. 08-22, mar. 2019. ISSN 2348-0335. Available at: <https://japtronline.com/index.php/JOAPR/article/view/159>. Date accessed: 06 apr. 2020. doi: https://doi.org/10.18231/2348-0335.2018.0014.


[1] BNFC, British National Formulary for Children “Ibuprofen.”: https://bnfc.nice.org.uk>drug>ibuprofen, cited 2 October, 2018.
[2] BP, British Pharmacopoeia Volumes I, II and V. Pharmaceutical Press, London, pp. 802, appendices V (A-H), X (B-G) (2013)
[3] Madaan V, Chanana A, Kataria MK, Bilandi A. Emulsion Technology and Recent Trends in Emulsion Applications. International Research Journal of Pharmacy, 5, 7 (2014)
[4] Nimberkar TP, Wanjari BE, Sanghi DK, Gaikwad NJ. Formulation and evaluation of sustained release multiple emulsion of hydroxprogesterone. Int J Pharm Pharm Sci, 4(1), 76-80 (2012)
[5] Omotosho JA, Florence AT, Whateley TL. Absorption and lymphatic uptake of 5-fluorouracil in the rat following oral administration of w/o/w multiple emulsions. Int. J. Pharm., 61, 51–56 (1990)
[6] Asuman B, Ongun MS. Delivery systems for antigens. Multiple emulsions: Technology and applications (Abraham A ed.) John Wiley and Sons, Inc., USA, pp. 293–306 (2008)
[7] Bhowmick M, Sonakpuriya P, Pandey G, Joshi A., Dubey B. Formulation and evaluation of multiple emulsion of valsartan. International Journal of PharmTech Research, 5(1), 132-146 (2013)
[8] Neeraj B, Siddharth P, Shikha A, Dishant G. A Review on Multiple Emulsions. International Journal of Pharmaceutical Erudition, 3(2), 22-30 (2013)
[9] Vaziri A, Warburton B. Slow release of chloroquine phosphate from taste masked w/o/w multiple emulsion. Journal of Microencapsulation, 11(6), 641 (1994)
[10] Laugel C, Baillet A, Piemi MPY, Marty JP, Ferrier D. Oil-in-water-in-oil multiple emulsions for prolonged delivery of hydrocortisone after topical application: comparison with simple emulsions. Int. J. Pharm., 160, 109-117 (1998)
[11] Florence AT, Whitehill D. The formulation and stability of multiple emulsion. Int. J. Pharm., 11, 277 (1982)
[12] Aryapak S, Ziarati P. Nutritive value of Persian walnut (Juglans regia L.) Orchards. American-Eurasian Journal of Agricultural and Environmental Science, 14(11), 1228-1235 (2014)
[13] Ayoola PB, Onawumi OOE, Faboya OOP. Chemical evaluation and nutritive values of Tetracarpidium conophorum (Nigerian walnut) seeds. Journal of Pharmaceutical and Biomedical Sciences, 11(15), 1-5 (2011)
[14] Grace MH, Warlick CW, Neff SA, Lila MA. Efficient preparative isolation and identification of walnut bioactive components using high-speed counter-current chromatography and LC-ESI-ITTOF-MS. Plants for Human Health Institute, Food Bioprocessing and Nutritional Sciences, 158, 229-238 (2014)
[15] Onawumi OOE, Faboya OOP, Ayoola PB. Chemical evaluation and nutritive values of African walnut leaf (Plukenetia conophora Müll.Arg.). International Journal of Herbal Medicine, 1(3), 122-126 (2013)
[16] Neeraja P, Amaleshwari M, Ravali G. Formulation and evaluation of nifedipine multiple emulsions. International Journal of Pharmaceutical, Chemical and Biological Sciences, 4(3), 673–680 (2014)
[17] Becher P. Emulsions: Theory and Practice. American Chemical Society Monograph, No.135. Rheinhold Publishing Corporation, New York (1957)
[18] Oladimeji FA. Formulation studies on essential oil of Lippia multiflora Moldenke for management of scabies. Ph.D thesis, Obafemi Awolowo University, Ile-Ife, Nigeria (2003)
[19] Sinha VR, Kumar A. Multiple Emulsions: An overview of formulation, characterization, stability and applications. Int. J. Pharm., 64(3), 191–199 (2002)
[20] Sherman P. Rheology of emulsion. Emulsion science. (Sherman P ed.) Academic Press, London, pp. 217-351 (1968)
[21] Omotosho JA, Law TK, Whateley TL, Florence AT. Methotrexate transport from the internal phase of multiple w/o/w emulsions. Journal of Microencapsulation, 6(2), 183-192 (1989)
[22] Nakhare S, Vyas SP. Prolonged release of rifampicin from internal phase multiple w/o/w emulsion systems. Indian Journal of Pharmaceutical Sciences, 57(2), 71-77 (1995)
[23] Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. Association of American Pharmaceutical Scientists Journal, 12(3), 263-271 (2010)
[24] Zuo J, Gao Y, Bou-chacra N, Löbenberg R. Evaluation of DDSolver software applications. Biomedical Research International, http://dx.doi.org/10.1155/2014/204925, cited 21 December, 2015
[25] Gurny R, Doelker E, Peppas NA. Modelling of sustained release of water-soluble drugs from porous, hydrophobic polymers. Biomaterials, 3, 27–32 (1982)
[26] Brazel CS,Peppas NA. Modeling of drug release from swellable polymers. Eur. J. Pharm. Biopharm, 49, 47–58 (2000)
[27] Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Biopharm, 13, 123-133 (2001)
[28] Bankole VO, Oladimeji FA. Evaluation of the kinetics and mechanism of piroxicam release from lipophilic and hydrophilic suppository bases. International Journal of Chem Tech Research, 10(1), 189-198 (2017)
[29] Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm. Sci., 50, 874 -875 (1961)
[30] 30. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas, NA. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 15(1), 25–35 (1983)
[31] Isong N, Alozie YE, Ekwere Y. Physicochemical properties of African walnut (Tetracarpidium conophorum) oil and its suitability for domestic and industrial uses. Nigerian Journal of Agriculture, Food and Environment, 9(3), 12–15 (2013)
[32] Agarwal SP, Rajesh K. Basics of pharmaceutical emulsions: A review. Physical Pharmacy. CBS Publisher, Delhi, India, pp. 177-186 (2007)
[33] Karleskind A. Manuel des corps gras. Association francaise pour l’etude des corps gras, Paris. 2, 787–792 (1992)
[34] Nkafamiya, MHM, Osemeahon, SA, Modibbo. Percentage oil yield and physicochemical properties of different groundnut (Arachis hypogea) species. African Journal of Food Science, 4(7), 418-421 (2010)
[35] Martin A, Swarbick J, Cammarata A. Physical Pharmacy, 3rd edition, Lea and Febiger, Philadelphia, USA, pp. 75-87; 445-68; 492-573 (1983)
[36] Patrick JS. Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition. Lippincott Williams and Wilkins, Philadelphia, USA, pp. 509-516; 561–576 (2006)
[37] Paul B. The Science and Practice of Pharmacy, Remington. Lippincott Williams and Wilkins, Philadelphia, USA, pp. 325-335, 759-760 (2005)
[38] McClements DJ. Food Emulsions: Principles, Practice and Techniques. CRC Press, New York, pp. 53-339 (1999)
[39] Vasiljevic D, Parojcic J, Primorac M, Vuleta G. An investigation into the characteristics and drug release properties of multiple w/o/w emulsion systems containing low concentration of lipophilic polymeric emulsifier. Int. J. Pharm., 309, 171–177 (2006)
[40] Tirnaksiz F, Kalsin O. A topical w/o/w multiple emulsions prepared with Tetronic 908 as a hydrophilic surfactant: Formulation, characterization and release study. Int J Pharm Pharm Sci, 8, 299–315 (2005)
[41] Omotosho JA. The effect of acacia, gelatin and polyvinylpyrrolidone on chloroquine transport from multiple w/o/w emulsions. Int. J. Pharm., 62, 81-84 (1990)
[42] Pal R. Shear viscosity behaviour of emulsions of two immiscible liquids. Journal of Colloid and Interface Science, 225(2), 359-366 (2000)
[43] Hou W, Papadopoulos KD. W/O/W and O/W/O globules stabilized with Span 80 and Tween 80. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 125, 181-187 (1987)
[44] Okubanjo OO, Odeku OA. Effect of interacting variables on the mechanical and release properties of chloroquine phosphate suppositories, ActaPharma. Sci., 51, 281-288 (2009)