Abstract
The preparation of solid lipid nanoparticles (SLNs) suffers from the drawback of poor incorporation of water-soluble drugs. The aim of this study was therefore to assess various formulation and process parameters to enhance the incorporation of a water-soluble drug (diclofenac sodium, DS) into SLNs prepared by the emulsion/solvent evaporation method. Results showed that the entrapment efficiency (EE) of DS was increased to approximately 100% by lowering the pH of dispersed phase. The EE of DS-loaded SLNs (DS-SLNs) had been improved by the existence of cosurfactants and increment of PVA concentration. Stabilizers and their combination with PEG 400 in the dispersed phase also resulted in higher EE and drug loading (DL). EE increased and DL decreased as the phospholipid/DS ratio became greater, while the amount of DS had an opposite effect. Ethanol turned out to be the ideal solvent making DS-SLNs. EE and DL of DS-SLNs were not affected by either the stirring speed or the viscosity of aqueous and dispersed phase. According to the investigations, drug solubility in dispersion medium played the most important role in improving EE.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alexy P, Lacik I, Simkova B et al (2004) Effect of melt processing on thermo-mechanical degradation of poly(vinyl alcohol)s. Polym Degrad Stab 85:823–830
Almeida AJ, Souto E (2007) Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv Drug Deliv Rev 59:478–490
Araujo J, Gonzalez E, Egea MA et al (2009) Nanomedicines for ocular NSAIDs: safety on drug delivery. Nanomedicine 5:394–401
Attama AA, Reichl S, Muller-Goymann CC (2008) Diclofenac sodium delivery to the eye: In vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int J Pharm 355:307–313
Baydoun L, Muller-Goymann CC (2003) Influence of n-octenylsuccinate starch on in vitro permeation of sodium diclofenac across excised porcine cornea in comparison to Voltaren ophtha. Eur J Pharm Biopharm 56:73–79
Bertocchi P, Antoniella E, Valvo L et al (2005) Diclofenac sodium multisource prolonged release tablets-a comparative study on the dissolution profiles. J Pharm Biomed Anal 37:679–685
Budhian A, Siegel SJ, Winey KI (2007) Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content. Int J Pharm 336:367–375
Castro GA, Coelho AL, Oliveira CA et al (2009) Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles. Int J Pharm 381:77–83
Cui FD, Shi K, Zhang LQ et al (2006) Biodegradable nanoparticles loaded with insulin–phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release 114:242–250
Galindo-Rodriguez S, Allemann E, Fessi H et al (2004) Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion and nanoprecipitation methods. Pharm Res 21:1428–1439
Govender T, Stolnik S, Garnett MC et al (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release 57:171–185
Haznedar S, Dortunc B (2004) Preparation and in vitro evaluation of Eudragit microspheres containing acetazolamide. Int J Pharm 269:131–140
Heiati H, Phillips NC, Tawashi R (1996) Evidence for phospholipid bilayer formation in solid lipid nanoparticles formulated with phospholipid and triglyceride. Pharm Res 13:1406–1410
Italia JL, Bhatt DK, Bhardwaj V et al (2007) PLGA nanoparticles for oral delivery of cyclosporine: nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral. J Control Release 119:197–206
Kaur IP, Bhandari R, Bhandari S et al (2008) Potential of solid lipid nanoparticles in brain targeting. J Control Release 127:97–109
Kocbek P, Baumgartner S, Kristl J (2006) Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int J Pharm 312:179–186
Liu J, Gong T, Wang CG et al (2007) Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization. Int J Pharm 340:153–162
Lucks JS, Muller RH (1991) Medication vehicles made of solid lipid particles (solid lipid nanospheres, SLN). EP 0605497
Mehnert W, Mader K (2001) Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev 47:165–196
Muchow M, Maincent P, Muller RH (2008) Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery. Drug Dev Ind Pharm 34:1394–1405
Muller RH, Runge SA (1998) Solid lipid nanoparticles (SLN) for controlled drug delivery. In: Benita S (ed) Submicron emulsions in drug targeting and delivery. Harwood Academic Publishers, Amsterdam, pp 219–234
Muller RH, Mader K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery-a review of the state of the art. Eur J Pharm Biopharm 50:161–177
Muller-Goymann CC (2004) Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration. Eur J Pharm Biopharm 58:343–356
Myers D (1999) Surfaces, interfaces and colloids: principles and applications, 2nd edn. Wiley, New York, pp 253–294
Pardeike J, Hommoss A, Muller RH (2009) Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 366:170–184
Patist A, Chhabra V, Pagidipati R et al (1997) Effect of chain length compatibility on micellar stability in sodium dodecyl sulfate/alkyltrimethylammonium bromide solutions. Langmuir 13:432–434
Peltonen L, Aitta J, Hyvonen S et al (2004) Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly(l)lactide nanoparticles. AAPS Pharm Sci Tech 5:E16
Schubert MA, Harms M, Muller-Goymann CC (2006) Structural investigations on lipid nanoparticles containing high amounts of lecithin. Eur J Pharm Sci 27:226–236
Shah KA, Date AA, Joshi MD et al (2007) Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery. Int J Pharm 345:163–171
Shahgaldian P, Da Silva E, Colemana AW et al (2003) Para-acyl-calix-arene based solid lipid nanoparticles (SLNs): a detailed study of preparation and stability parameters. Int J Pharm 253:23–38
Song CX, Labhasetwar V, Murphy H et al (1997) Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. J Control Release 43:197–212
Song XR, Zhao Y, Wu WB et al (2008) PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: Systematic study of particle size and drug entrapment efficiency. Int J Pharm 350:320–329
Talukder MMR, Hayashi Y, Takeyama T et al (2003) Activity and stability of Chromobacterium viscosum lipase in modified AOT reverse micelles. J Mol Catal B: Enzym 22:203–209
Tesch S, Schubert H (2002) Influence of increasing viscosity of the aqueous phase on the short-term stability of protein stabilized emulsions. J Food Eng 52:305–312
Valot P, Baba M, Nedelec JM et al (2009) Effects of process parameters on the properties of biocompatible ibuprofen-loaded microcapsules. Int J Pharm 369:53–63
Wan F, You J, Sun Y et al (2008) Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro. Int J Pharm 359:104–110
Acknowledgment
This work was financially supported by the Jiangsu Natural Science Funds (Project No. BK2009420).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Liu, D., Jiang, S., Shen, H. et al. Diclofenac sodium-loaded solid lipid nanoparticles prepared by emulsion/solvent evaporation method. J Nanopart Res 13, 2375–2386 (2011). https://doi.org/10.1007/s11051-010-9998-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-010-9998-y