PREPARATION AND IN VITRO EVALUATION OF MONTELUKAST SODIUM ORAL NANOEMULSION
Keywords:Montelukast sodium, nanoemulsion, oleic acid, ultrasonication
Objective: Oral nanoemulsion (NE) represent one of the newest technology to enhance intestinal drug permeability, bioavailability and facilitate swallowing of the oral dosage form.
Methods: In this study, montelukast sodium (MS) nanoemulsions (NEs) were formulated by ultra-sonication using different surfactants (tween 20, tween 60 and tween 80) in different surfactant: co-surfactant (ethanol) ratios (Smix). The prepared NEs were evaluated for different parameters including droplet size (DS) using zetasizer as a function of ultra-sonication time, dispersibility, phase separation, conductivity, percent transmittance, optical transparency, in vitro release in addition to morphology using transmission electron microscopic (TEM).
Results: The results revealed that F3 was the optimum formula having an average DS 32.95Â±2.8 nm after 5 min ultra-sonication assured by zetasizer and TEM, furthermore, a clear to bluish NE was formed after aqueous dilution with high conductivity (59.2Â±1.76 Î¼s/cm) which indicated the formation of O/W NE. In addition, an optically clear NE was formed with (88.6Â±2.1) % transmittance with no sedimentation, creaming or separation after centrifugation signifying the formation of a stable NE. Finally, F3 showed faster dissolution rate (92.45%Â±1.66) after 30 min compared to other formulas.
Conclusion: The net result of this study is the formulation of a stable oral NE containing MS which presents new easily swallowed dosage form that may enhance drug permeability as well as it may reduce drug metabolism leading to improving bioavailability for asthmatic patients.
Harikrishna D, Svitlana S, Feng Z, Jessica M, Galina G, Albert O, et al. Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs. Pharm Nanotechnol 2013;102:3808â€“15.
Nidhal KM, Anas TA, Zainab HM. Application of the new oroslippery technology in the preparation of enteric slippery coated tablet of naproxen. Int J Pharm Pharm Sci 2017;9:198-204.
Zainab HM, Nidhal KM. New easily swallowed tablets with a slippery coating for the antihypertensive drug valsartan. UK J Pharm Biosci 2015;3:9-19.
Vivek PC, Dhaval S. A review on novel emulsification technique: a nanoemulsion. J Pharm Toxicol Stud 2017;5:29-37.
Halah HA, Ahmed AH. Oral nanoemulsions of candesartan cilexetil: Formulation, characterization and in vitro drug release studies. AAPS J 2017;3:2-16.
Setya S, Talegonkar S, Razdan BK. Nanoemulsions: formulation methods and stability aspects. World J Pharm Pharm Sci 2014;3:2214â€“28.
Kriwet K, Muller-Goymann CC. Diclofenac release from phospho-lipid drug systems and permeation through excised human stratum corneum. Int J Pharm 1995;125:231-42.
Nirmala MJ, Allanki S, Mukherjee A, Chandrasekaran N. Azithromycin: essential oil based nanoemulsion drug delivery system. Int J Pharm Pharm Sci 2010;5:236-8.
Neeharika MS, Jodi BJ. Chronotherapeutics: an optimizing approach to synchronize drug delivery with circadian rhythm. J Cancer Res 2015;2:31-40.
Chin Yin C, Hsinchu H. Liquid pharmaceutical foreign application priority data composition of leukotrene antagonsts. United States Patent Application Publication 0147482 A1; 2006.
Delmas T, Piraux H, Couffin AC, Texier I, Vinet F, Poulin P, et al. How to prepare and stabilize very small nanoemulsions. Langmuir 2011;27:1683-92.
Sarwar BC, Sidharth SJ, Ch NP, Mohammad R, Suryakanta S, Sruti J, et al. Development of solid self-nano emulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloids Surf B 2013; 101:414â€“23.
Beg S. Ultrasonic emulsification of food-grade nanoemulsion formulation and evaluation of its bactericidal activity. Colloids Surf B 2013;101:414â€“23.
Schmolka IR. Artificial skin. Int J Biomed Mater Res 1972;6:571â€“82.
Rajeev S, Gali VS, Pankaj S. Formulation, development and in vitro evaluation of mucoadhesive bilayered buccal patches of montelukast sodium. Int J Pharm Pharm Sci 2012;4:484-97.
Thonge SV, Mrudula HB, Harpreet KK, Mandeep D. Taste masked formulation of montelukast sodium for the pediatric population and its evaluation. Asian J Pharm Health Sci 2016;6:1536-49.
Mohammad A, Sahabjada, Juber A, Arshad H, Badaruddeen, Arshad M, et al. Development of a new rutin nanoemulsion and its application on the prostate carcinoma pc3 cell line. Excli J 2017;16:810-23.
Nidhal KM, Yasser QA. Application of nanoemulsion technology for preparation and evaluation of intranasal mucoadhesive nano-in-situ gel for ondansetron HCl. JGPT 2018;10:431-42.
Setya S, Negi P, Razdan BK, Talegaonkar S. Design, development and in vitro investigation of water in oil nanoemulsion for transdermal delivery. World J Pharm Pharm Sci 2014;3:1495-512.
Antonio M, Alvarez R, RodrÃguez ML. Lipids in pharmaceutical and cosmetic preparations. Grasasy Aceites 2000;51:74-96.
Kalra R. Development and characterization of nanoemulsion formulations for transdermal delivery of aceclofenac: research. IJDFR 2010;1:359-86.
Gallik S, Rob L, Dean RL. Understanding beerâ€™s law: An interactive laboratory presentation and related exercises. JLCE 2014;2:44-9.
Hussein AA. Preparation and evaluation of liquid and solid self-micro emulsifying drug delivery system of mebendazole. Iraqi J Pharm Sci 2014;23:89-100.
Sonal S, Poornima N, Razdan BK, Sushama T. Design, development and in vitro investigation of water in oil nanoemulsion for transdermal delivery. World J Pharm Pharm Sci 2014;3:1495-512.
Samira K, Fariborz K, Amir A. Design and evaluation of the oral nanoemulsion drug delivery system of mebudipine. Drug Delivery 2016;23:2035â€“43.
Ming Jun T, Yaw Syan F, Yu Hsuan L, Yaw Bin H, Pao Chu W. The effect of nanoemulsion as a carrier of the hydrophilic compound for transdermal delivery. Plos One 2014;9:1-7.
Tamilvanana S, Senthilkumarb SR, baskarb R, Thenrajan Raja, Sekharanb TR. Manufacturing techniques and excipients used during the formulation of oil-in-water type nanosized emulsions for medical applications. J Excipients Food Chem 2010;1:11-29.
Manuel GM, Philip ES. Flavor and compositional comparison of orange essences and essence oils produced in the United States and in brazil. JAFC 1990;38:799-801.
Allen LV, Popovich NG, Ansel HC. editors. Disperse system. Philadilphia: Lippincott Williams and Wilkins Publishing; 2011.
Ma TY, Hollander D, Krugliak P, Katz PK. PEG 400, a hydrophilic molecular probe for measuring intestinal permeability. Gastroenterology 1990;98:39â€“46.
Ankur GH, Burak ET, Alan H, Patrick SD. Nanoemulsions: formation, properties and applications. Royal Society of Chemistry 2016:12;2826-41.
Beg S. Development of solid self nano emulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloids Surf B 2013;101:414â€“23.
Tadros TF. editor. Emulsion formation, stability, and rheology. Germany: Wiley-VCH Verlag GmbHand Co. KGaA, Weinheim; 2013.
Chhabra G, Chuttani K, Mishra AK, Pathak K. Design and development of nanoemulsion drug delivery system of amlodipine besilate for improvement of oral bioavailability. Drug Dev Ind Pharm 2011;37:907â€“16.
McClements DJ. Colloidal basis of emulsion colour. Curr Opin Colloid Interface Sci 2015;7:451â€“5.
Leong TSH, Wooster TJ, Kentish SE, Ashokkumar M. Minimising oil droplet size using ultrasonic emulsification. Ultrason Sonochem 2009;16:721â€“7.
Avachat AM, Patel VG. Self-nanoemulsifying drug delivery system of stabilized ellagic acidâ€“phospholipid complex with improved dissolution and permeability. SPS 2015;23:276â€“89.
Martin AN, Sinko PJ. Martin's physical pharmacy and pharmaceutical sciences. In: Lippincott Williams, Wilkins: Sinko PJ. editors. Interfacial phenomena. 6th edi. London: Lea and Febiger; 2011. p. 365-7.
Mathew DS, Juang RS. Role of alcohols in the formation of inverse microemulsions and back extraction of proteins/ enzymes in a reverse micellar system. Sep Purif Technol 2007;53:199â€“215.