Abstract
Self microemulsifying drug delivery systems (SMEDDS) are defined as isotropic mixtures of natural or synthetic oils, surfactants and co-solvents/co-surfactants. Upon mild agitation followed by dilution in aqueous media, such as GI fluids, these systems can form fine oil in water o/w microemulsion. The purpose of this study was to formulate SMEDDS containing mebendazole. Labrafil M2125 CS (an oil), Tween 20 (a surfactant), and Maisine 35-1 (a cosurfactant) were used to formulate SMEDDS. Effect of concentrations of oil and surfactant on emulsification process and in vitro drug release (percent cumulative drug release) was studied using 32 factorial design. Multiple regression analysis data and response surfaces obtained showed that viscosity increased significantly with increasing amount of co-surfactant. Whereas, decrease in emulsification time, it may decreases average droplet size of resultant microemulsion and rapid drug release. The drug release from the formulation increased with increasing amount of surfactant concentration increases solubility of drug in system. Prepared SMEDDS produced acceptable properties of immediate-release dosage forms. The L5 formulation was found to be optimized on basis of high percent cumulative drug release. And it is evaluated by globule size and zeta potential indicates globule size is in micrometer range and good stable formulation. It may expect to increase the bioavailability of mebendazole as solubility enhances.
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Abbaspour M, Jalayer N, Makhmalzadeh BS (2014) Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadine by extrusion-spheronization. Adv Pharm Bull 4(2):113–119. doi:10.5681/apb.2014.018
Ahmed J, Kohli K, Mir SR, Amin S (2011) Formulation of self nanoemulsifying drug delivery system for telmisartan with improved dissolution and oral bioavailability. J Dispers Sci Technol 32:958–968. doi:10.1080/01932691.2010.488511
Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S (2007) Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharma 57:315–332. doi:10.3478/v10007-007-0025-5
Baek MK, Lee JH, Cho YH, Kim HH, Lee GW (2013) Self-microemulsifying drug delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation. Int J Nanomed 8:167–176. doi:10.2147/IJN.S37338
Bajaj A, Rao M, Khole I, Munjapara G (2013) Self nanoemulsifying drug delivery system of cefpodoxime proxetil containing tocopherol polyethylene glycol. Drug Dev Ind Pharm 39(5):635–645. doi:10.3109/03639045.2012.683440
Balakrishnan P, Lee BJ, Oh DH, Kim JO, Hong MJ, Jee JP, Kim JA, Yoo BK, Woo JS, Yong CS, Choi HG (2009) Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system. Eur J Pharm Biopharm 72:539–545. doi:10.1016/j.ejpb.2009.03.001
Balakumar K, Raghavan CV, Selvan NT, Rahman SH (2013) Self emulsifying drug delivery system: optimization and its prototype for various compositions of oils, surfactants and co-surfactants. J Pharm Res 6:510–514. doi:10.1016/j.jopr.2013.04.031
Block JH, Beale JM (2004) Wilsons and grisvolds textbook of organic medicinal and pharmaceutical chemistry, 11th ed edn. Lippincott williams and Wilkins, Philadelphia, pp 265–266
Chambin O, Berard V, Rochat MH, Pourcelot Y (2002) Dry absorbed emulsion, dissolution behaviour of an intrinsic formulation. Int J Pharm 235:169–178. doi:10.1016/s0378-5173(01)00991-7
Costa P, Lobo MS (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci 13:123–133. doi:10.1016/s0928-0987(01)00095-1
Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharm Drug Res 67(3):217–223
Dharankar SD, Parakh DR, Patil MP, Kshirsagar SJ (2015) Spray-dried solid self-emulsifying delivery system of ketoprofen: development and its characterization. Dry Technol 33:2002–2011. doi:10.1080/07373937.2015.1039541
Dixit RP, Nagarsenker MS (2008) Self nanoemulsifying granules of ezetimibe: design, optimization and evaluation. Eur J Pharm Sci 35:182–192. doi:10.1016/j.ejps.2008.06.013
Eaid AMM (2012) The effect of surfactant blends on production of self emulsifying drug delivery system. Int J Pharm Front Res 2(2):21–31
Florey K (2005) Analytical profile of drug substances, vol 16, 1st edn. Academic press, New York
Goddeeris C, Coacci J, Mooter GV (2007) Correlation between digestion of the lipid phase of SMEDDS and release of the anti-HIV drug UC 781 and the anti-mycotic drug enilconazole from SMEDDS. Eur J Pharm Biopharm 66(2):173–181. doi:10.1016/j.ejpb.2006.10.005
Government of India, Indian Pharmacopoeia Commission (2014) Ministry of health and family welfare. Indian Pharmacopoeia, Controller of publications, Ghaziabad, vol I and II, pp 498, 2154–2155
Gursoy RN, Benita S (2004) Self emulsifying drug delivery system (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacoth 58:173–182. doi:10.1016/j.biopha.2004.02.001
Hadkar UB (2008) A handbook of practical physical pharmacy and physical pharmaceutics, 2nd edn. Nirali Prakashan, Pune, pp 68–69
Hu X, Lin C, Chen D, Zhang J, Liu Z, Wu W, Song H (2012) Sirolimus solid self-microemulsifying pellets: formulation development, characterization and bioavailability evaluation. Int J Pharm 438:123–133. doi:10.1016/j.ijpharm.2012.07.055
Jadhav KR, Shetye SL, Kadam VJ (2010) Design and evaluation of microemulsion based drug delivery system. Int J Adv Pharm Sci 1:156–166. doi:10.5138/164
Jeffery GH, Bassett J, Mendham J, Denney RC (1989) Vogel’s textbook of quantitative chemical analysis, 5th edn. Longman scientific technical, New York, pp 726–730
Khoo SM, Humberstone AJ, Porter CJH, And Edwards GA, Charman WN (1998) Formulation design and bioavailability assessment of lipidic self emulsifying formulations of halofantrine. Int J Pharm 167:155–164. doi:10.1016/s0378-5173(98)00054-4
Kohli K, Chopra S, Dhar D, Arora S, Khar RK (2010) Self emulsifying drug delivery systems: an approach to enhance oral bioavailability. Drug Discov Today 15:958–965. doi:10.1016/j.drudis.2010.08.007
Kommuru TR, Gurley B, Khan MA, Reddy IK (2001) Self emulsifying drug delivery systems of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm 212:233–246. doi:10.1016/s0378-5173(00)00614-1
Mahmoud EA, Bendas ER, Mohamed MI (2009) Preparation and evaluation of self nanoemulsifying tablets of carvedilol. AAPS PharmSciTech 10(1):183–192. doi:10.1208/s12249-009-9192-7
Milovic M, Djuris J, Djekic L, Vasiljevic D, Ibric S (2012) Characterization and evaluation of solid self-microemulsifying drug delivery systems with porous carriers as systems for improved carbamazepine release. Int J Pharm 436:58–65. doi:10.1016/j.ijpharm.2012.06.032
Onoue S, Uchida A, Kuriyama K, Nakamura T, Seto Y, Kato M, Hatanaka J, Tanaka T, Miyoshi H, Yamada S (2012) Novel solid self-emulsifying drug delivery system of coenzyme Q10 with improved photochemical and pharmacokinetic behaviours. Eur J Pharm Sci 46:492–499. doi:10.1016/j.ejps.2012.03.015
Pandya BD, Shah SH, Shah N (2015) Bioavailability enhancement of poorly soluble drugs by self micro emulsifying drug delivery system (SMEDDS): a review. J Pharm Sci Biosci Res 5(2):187–196
Parakh DR, Patil MP (2014) Comparison of in vitro dissolution profiles of marketed dicyclomine hydrochloride tablets. Int J Adv Pharm Sci 5(3):2109–2119
Parakh DR, Patil MP, Dashputre NL, Kshirsagar SJ (2015a) Development of self microemulsifying drug delivery system of mebendazole by spray drying technology: characterization in-vitro and in-vivo evaluation. Dry Technol. doi:10.1080/07373937.2015.1090447
Parakh DR, Patil MP, Shinde GP (2015b) Self micro-emulsifying drug delivery system: approach to improve solubility and permeability. Int J Inst Pharm Life Sci 5(4):21–37
Patel PV, Patel HK, Panchal SS, Mehta TA (2013a) Self micro-emulsifying drug delivery system of tacrolimus: formulation, in vitro evaluation and stability studies. Int J Pharm Invest 3(2):95–104. doi:10.4103/2230-973X.114899
Patel RB, Patel MR, Bhatt KK, Patel BG (2013b) Formulation consideration and characterization of microemulsion drug delivery system for transnasal administration of carbamazepine. Bull Fac Pharm Cairo Univ 51(2):243–253. doi:10.1016/j.bfopcu.2013.07.002
Patil P, Joshi P, Paradkar A (2004) Effect of formulation variables on preparation and evaluation of gelled self-emulsifying drug delivery system (SEDDS) of ketoprofen. AAPS PharmSciTech 5(3):1–8. doi:10.1208/pt050342
Qi X, Wang L, Zhu J, Hu Z, Zhang J (2011) Self double emulsifying drug delivery system (SDDDS): a new way for oral delivery of drugs with high solubility and low permeability. Int J Pharm 409:245–251. doi:10.1016/j.ijpharm.2011.02.047
Qureshi MJ, Mallikarjun C, Kian WG (2015) Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: a study in diet induced hyperlipidemic rabbits. Asian J Pharm Sci 10(1):40–56. doi:10.1016/j.ajps.2014.08.003
Rowe CR, Sheskey PJ, Quinn ME (2009) Handbook of pharmaceutical excipients, 6th edn edn. Pharmaceutical press, New York
Sapraa K, Saprab A, Singha SK, Kakkarb S (2012) Self emulsifying drug delivery system: a tool in solubility enhancement of poorly soluble drugs. Indo Global J Pharm Sci 2(3):313–332
Shaji J, Jadhav D (2010) Newer approches to self emulsifying drug delivery system. Int J Pharm Pharm Sci 2(1):37–42
Shen H, Zhong M (2006) Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. J Pharm Pharmacol 58:1183–1191. doi:10.1211/jpp.58.9.0004
Singh B, Dahiya M, Kharb V, Ahuja N (2005) Optimizing drug delivery systems using systematic design of experiments. Part II: retrospect and prospects. Crit Rev Ther Drug Carr Syst 22(3):215–294. doi:10.1615/CritRevTherDrugCarrierSyst.v22.i3.10
Singh AK, Chaurasiya A, Awasthi A, Mishra G, Asati D, Khar RK, Mukherjee R (2009a) Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system. AAPS PharmSciTech 10(3):906–916. doi:10.1208/s12249-009-9281-7
Singh B, Bandopadhyay S, Kapil R, Singh R, Katare OP (2009b) Self emulsifying drug delivery system: formulation, development, characterization and applications. Crit Rev Ther Drug Carr Syst 26:427–521
Tripathi KD (2008) Essentials of medical pharmacology, 6th edn. Jaypee brothers medical publishers Pvt Ltd, New Delhi, pp 808–810
United States Pharmacopoeial Convention (2006) The United States pharmacopoeia 29, National formulary 24. Twinbrook parkway, Rockville, p 1316
Villar AMS, Naveros BC, Campmany AC, Trenchs MA, Rocabert CB, Bellowa LH (2012) Design and optimization of self nanoemulsifying drug delivery systems for enhanced dissolution of gemfibrozil. Int J Pharm 431:161–175. doi:10.1016/j.ijpharm.2012.04.001
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The author expresses the gratitude to Trustees, MET’s Institute of Pharmacy, Bhujbal Knowledge City, Adgaon, Nashik for providing necessary facilities and constant support. The author is also thankful to Gattefosse, France, Abitec Pvt. Ltd., Mumbai and Holden Pharmaceuticals, Sinnar, Nashik for providing gift sample for research.This article does not contain any studies with human and animal subjects performed by any of the authors. All the Authors declare that they have no conflict of interest.
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Parakh, D.R., Patil, M.P., Sonawane, S.S. et al. Application of factorial design approach in development and evaluation of self microemulsifying drug delivery system (SMEDDS) of mebendazole. Journal of Pharmaceutical Investigation 47, 507–519 (2017). https://doi.org/10.1007/s40005-016-0279-3
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DOI: https://doi.org/10.1007/s40005-016-0279-3