DSpace at VNU: Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method

DSpace at VNU: Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by...

This article was downloaded by: [Ondokuz Mayis Universitesine] On: 12 November 2014, At: 16:45 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Journal of Experimental Nanoscience Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tjen20 Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method a b b Le Thi Mai Hoa , Nguyen Tai Chi , Le Huu Nguyen & Dang Mau Chien a a Laboratory for Nanotechnology (LNT), Vietnam National University , Community 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City , Vietnam b Faculty of Pharmacy, The University of Medicine and Pharmacy at Ho Chi Minh City , 41 Dinh Tien Hoang, Ben Nghe Ward, District 1, Ho Chi Minh City , Vietnam Published online: 14 Jul 2011 To cite this article: Le Thi Mai Hoa , Nguyen Tai Chi , Le Huu Nguyen & Dang Mau Chien (2012) Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method, Journal of Experimental Nanoscience, 7:2, 189-197, DOI: 10.1080/17458080.2010.515247 To link to this article: http://dx.doi.org/10.1080/17458080.2010.515247 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content This article may be used for research, teaching, and private study purposes Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 systematic supply, or distribution in any form to anyone is expressly forbidden Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions Journal of Experimental Nanoscience Vol 7, No 2, March–April 2012, 189–197 Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method Le Thi Mai Hoaa*, Nguyen Tai Chib, Le Huu Nguyenb and Dang Mau Chiena Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 a Laboratory for Nanotechnology (LNT), Vietnam National University, Community 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam; bFaculty of Pharmacy, The University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam (Received 25 January 2010; final version received August 2010) We have prepared polymeric drug nanoparticles by oil in water (O/W) emulsion solvent evaporation method We used acetone as solvent for polymer and water as non-solvent The purpose of this study is to use the emulsion solvent evaporation method in order to prepare nanoparticles and to investigate the effects of the various processing parameters to the characteristics of the nanoparticles In this research, we use two different forms of acrylic polymers, Eudragit E100 and Eudragit RS It was found that the size of the nanoparticles depends on different parameters such as the polymer concentration in the organic solvent, surfactant concentration and the volume ratio of oil and water phases The morphology structure is investigated by transmission electron microscope (TEM) TEM images confirmed that the nanoparticles produced were spherical in shape and the successfully prepared nanoparticles with size 80 nm The size distribution is measured by laser dynamic light scattering The size distribution of the nanoparticles was found in the range from 50 to 150 nm Investigation of Fourier transform infrared spectroscopy indicated the absence of the interactions between the drug and polymer X-ray diffraction patterns of nanoparticles containing ketoprofen, Eudragit E100 and Eudragit RS showed the amorphous structure Keywords: drug delivery; Eudragit; emulsion evaporation method; polymeric nanoparticle; ketoprofen Introduction Nanoparticle of drugs involves forming drug-loaded particles with diameters ranging from to 1000 nm Nanoparticles are defined as solid, submicron-sized drug carriers that may or may not be biodegradable [1,2] Drug nanoparticles can be further classified into nanocapsules and nanospheres based on their structure [3] Nanocapsules are vesicular systems in which the drug is confined to a cavity consisting of an inner liquid core surrounded by a polymeric membrance Nanospheres have a matrix type of strucutre Drugs may be absorbed at the sphere surface or encapsulated within the particle The drug *Corresponding author Email: ltmhoa@vnuhcm.edu.vn ISSN 1745–8080 print/ISSN 1745–8099 online ß 2012 Taylor & Francis http://dx.doi.org/10.1080/17458080.2010.515247 http://www.tandfonline.com Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 190 L.T.M Hoa et al is either solubilised in the polymer matrix to form an amorphous particle or embedded in the polymer matrix as crystallites [4] Several microencapsulation methods are available for the preparation of drug nanoparticles In the general microencapsulation technique using oil in water (O/W) emulsion system, the drug is dissolved, dispersed or emulsified in an organic polymer solution, which is then emulsified in an external aqueous or oil phase As the organic solvent is removed by evaporation, the drug and polymer are precipitated in the droplets, thus forming the nanosphere or nanocapsules The emulsion solvent evaporation technique was fully developed at the end of the 1970s and has been used successfully in the preparation of microspheres made from several biocompatible polymers such as poly(D,L-lactide-co-glycolide) [5,6] and Eudragit [7] More recently, an emulsion solvent diffusion method was proposed by Kawashima et al [8,9] The technique of emulsion solvent evaporation offers several advantages; it is preferred to other preparation methods such as spray drying, sonication and homogenisation, etc., because it requires only mild conditions such as ambient temperature and constant stirring Thus, a stable emulsion can be formed without compromising the activity of the drug The general emulsification solvent evaporation method used to produce nanoparticles involves a number of processing and materials parameters: power and duration of energy applied, aqueous phase volume, polymer and drug concentration in the organic phase, polymer molecular weight, polymer end groups, solvent volume and surfactant concentration Each of these processing and materials parameters influences the size and/or the drug content of the nanoparticles In drug delivery, nanoparticles should readily be biocompatible and biodegradable These properties, as well as targeting and controlled release, can be affected by nanoparticle material selection and by surface modification Materials such as synthetic polymers, proteins or other natural macromolecules are used in the preparation of nanoparticles Drug nanoparticles have potential applications in the administration of therapeutic molecules such as tissue targeting in cancer therapy, controlled release, carrier action for the delivery of peptides and increase in the solubility of drug [10] The purpose of this study is to use the emulsion solvent evaporation method in order to prepare nanoparticles using two different forms of acrylic polymers, Eudragit E100 and Eudragit RS, and to investigate the effect of various processing parameters on particle size and the characteristics of nanoparticles The processing parameters include polymer concentration in the organic phase, polyvinyl alcohol (PVA) concentration in the aqueous phase, the volume ratio of oil and water phases The drug material used is ketoprofen, widely used in the treatment of rheumatoid arthritis and osteoarthritis Experimental 2.1 Materials The pharmaceutical drug is a well-known anti-inflammatory agent, the generic name of which is ketoprofen It is made up of three groups: a phenyl group (–C6H5), a benzoyl group (–C6H4–CO) and an acetic chain (–CH–COOH) Ketoprofen is practically not soluble in water Journal of Experimental Nanoscience 191 The polymers used in this study are Eudragit E100 and Eudragit RS They are insoluble in acid and water, whereas they are soluble in organic solvents such as acetone, ethanol, etc Bidistilled water was used as non-solvents PVA was used as an emulsifying agent All materials were obtained from commercial sources and used as received: ketoprofen (USP-30; Roăhm Pharma, Darmstadt, Germany), Eudragit E100, Eudragit RS (Merck, Germany), PVA, acetone (Merck, German) Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 2.2 Preparation of the drug nanoparticles In this study, nanoparticles are prepared by emulsification solvent evaporation method using sonication An organic phase consisting of polymer (Eudragit E100 or RS) and drug (ketoprofen) dissolved in acetone (10 mL) This organic phase is added to an aqueous phase containing a surfactant (PVA, concentration 0.5%, 90 mL) to form an O/W type emulsion The volume ratio of oil and water phases was : This emulsion is broken down into nanodroplets by applying external energy through a sonicator These nanodroplets form nanoparticles upon evaporation of the highly volatile organic solvent The organic solvent evaporates during magnetic stirring at 300 rpm under atmospheric condition for h We studied the effect of various processing parameters on particle size The processing parameters include polymer concentration in the organic phase, PVA concentration in the aqueous phase and volume ratio of oil and water phases 2.3 Characterisation of nanoparticles We investigate the characterisation of nanoparticles, such as particle size and size distribution, morphology, crystallinity The particle size distribution was determined by dynamic light scattering (HORIBA LB-550-Japan) Infrared (IR) absorption spectra of raw materials and nanoparticles in the wavelength region 4000–400 cmÀ1 were recorded using a Fourier transform infrared (FT-IR) spectrometer (TEMSORTM37 – Bruner, USA) Particle morphology were observed using a transmission electron microscope (TEM; JEM-1400, Japan) using an acceleration voltage of 100 kV The crystallinity of the particles was studied using X-ray diffraction (XRD; D8 Advance – Bruker, German) Results and discussion 3.1 Effect of various processing parameter on the size of particles 3.1.1 Effect of polymer concentration in the organic phase The ketoprofen nanoparticles were prepared using polymer Eudragit E100, the volume ratio of oil and water phases was : 9, the PVA concentration in the aqueous phase was 0.5% The polymer concentration is varied from 3% (w/v) to 15% (w/v) Figure shows the effect of polymer concentration in the organic phase on the particle size An increase in 192 L.T.M Hoa et al 300 Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 Particle size (nm) 250 200 150 100 50 0 10 Polymer concentration (mg 15 20 ml–1) Figure Effect of polymer concentration in the organic phase on the particle size the concentration of polymer in a fixed volume of organic solvent leads to a gradual increase in nanoparticle diameter Increasing polymer concentration causes increase in the viscosity, thus leading to an increase of the emulsion droplet size The viscous forces oppose the shear stresses in the organic phase and the final size and size distribution of particles depends on the net shear stress available for droplet breakdown The importance of polymer concentration in controlling the size of particles produced by the general emulsification process has previously been reported for other poly(lactic-co-glycolic acid)/ poly lactic acid (PLGA/PLA) system [11] 3.1.2 Effect of PVA concentration in the aqueous phase The ketoprofen nanoparticles were prepared using polymer Eudragit E100; the volume ratio of oil and water phases was : 9; the polymer concentration is 5% The PVA concentration in the aqueous phase is varied from 0.5% (w/v) to 2% (w/v) Figure shows the effects of PVA concentration in the aqueous phase on the particles size As the PVA concentration increases, the size of particles gradually increases due to high aqueous phase viscosity, the viscosity increase reduces the net shear stress available for droplet breakdown Zweers et al have reported an increase in the size of PLGA nanoparticles at high PVA concentrations [11] 3.1.3 Effect of the volume ratio of oil and water phases The ketoprofen nanoparticles were prepared using polymer Eudragit E100; the polymer concentration was 5% (w/v); the PVA concentration in the aqueous phase was 0.5% (w/v) The volume ratio of oil and water phases was varied Figure shows the effects of the Journal of Experimental Nanoscience 400 350 250 200 150 100 50 0.5 1.5 2.5 PVA concentration (%) Figure Effect of PVA concentration in the aqueous phase on the particle size 1000 800 Particle size (nm) Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 Particle size (nm) 300 600 400 200 0.2 0.4 0.6 Oil/ Water ratio 0.8 Figure Effect of the volume ratio of oil and water phases on the particle size 193 Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 194 L.T.M Hoa et al Figure TEM images of the nanoparticles containing: 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 (a) and 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS (b) volume ratio of oil and water phases on the particle size As the volume ratio of oil and water phases is higher than 0.6, the size of particles increases rapidly 3.2 The charateristics of nanoparticle The morphology of nanoparticles prepared was studied using TEM Figure 4(a) shows TEM images of the nanoparticles containing 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 Figure 4(b) shows TEM images of nanoparticles containing 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS In both Figure 4(a) and (b), crystallinity or grain boundaries were not found TEM images show that the nanoparticles were spherical, amorphous and smooth The size of the particles was 80 nm The formation of an amorphous polymer-drug structure has been observed IR spectroscopy was used to study the interactions between the drug and the polymers Figure shows IR spectra of the nanoparticles at a wavenumber range 4000–400 cmÀ1 Ketoprofen has a carboxylic acid group, which can interact with the function groups of the polymer The carbonyl peaks in the IR spectra of ketoprofen were recorded at 1694 and 1654 cmÀ1 From Figure 5, it can be seen that the Eudragit E100 and Eudragit RS materials exhibit quite similar spectra The strong stretching vibration of the carbonyl moiety of ester groups could be identified for both the materials at 1732 cmÀ1 For the nanoparticles containing ketoprofen, Eudragit E100 and Eudragit RS, the position of the ester peak at 1732 cmÀ1 was not changed The carboxylic acid group of the ketoprofen molecule interacted with the polymer, leading to the disruption of the carbonxylic acid dimer of the crystalline ketoprofen Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 Journal of Experimental Nanoscience 195 Figure Infrared spectra at wavenumber of 4000 to 400 cmÀ1 of the nanoparticles containing: (a) 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 and (b) 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS Eudragit E100 is a polymer containing secondary amino groups capable of accepting a proton from an acid molecule The peaks correspoding to the amino groups have been identified at 2820 and 2770 cmÀ1 However, any change in the position of these peaks was not observed when ketoprofen was incorporated in the nanoparticles Therefore, it was concluded that ketoprofen drug mainly interacted with ester groups of the Eudragit E100 polymer, similar to Eudragit RS Figure shows the particle size distribution of nanoparticles containing: ketoprofen and Eudragit E100 (Figure 6(a)), ketoprofen and Eudragit RS (Figure 6(b)) Size distribution were determined by dynamic light scattering in aqueous solution, the size of the particles was in the range from 50 to 150 nm and the mean diameter was 80 nm Based on these results, we can see the sonication method is suited to produce small size nanoparticles (5300 nm diameter) with narrow size distribution Figure shows XRD patterns of the nanoparticles: 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 (Figure 7(a)), 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS (Figure 7b) In Figure 7(a) and (b), XRD showed diffraction pattern of the amorphous structure and no crystallinity We can conclude that the nanoparticles prepared was amorphous, as peaks corresponding to diffraction from drug crystal lattice were not detected Conclusion Polymeric drug nanoparticles were prepared by emulsion solvent evaporation method We investigated the effect of various processing parameters on particle size and characteristics 196 L.T.M Hoa et al (a) 15.00 q (%) Undersize 100.0 0.001 Diameter (nm) (b) 16.00 1.000 6.000 Undersize 100.0 q (%) Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 1.000 1.000 0.001 Diameter (nm) 1.000 6.000 Figure The particle size distribution of nanoparticles containing: (a) 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 and (b) 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS Figure XRD patterns of the nanoparticles containing: 10% (w/w) ketoprofen and 90% (w/w) Eudragit E100 (a) and 10% (w/w) ketoprofen and 90% (w/w) Eudragit RS (b) of nanoparticle Increase in different parameters such as the polymer concentration in the organic solvent, surfactant concentration, the volume ratio of oil and water phases led to increase in the size of particles The TEM observation shows the surface morphological features; morphology of particles was spherical and homogenerous The size distribution Journal of Experimental Nanoscience 197 of the nanoparticles was found in the range from 50 to 150 nm and the mean diameter was 80 nm The interaction between the drug and the polymer was determined by FT-IR The carboxylic group of the ketoprofen molecule interacts with the Eudragit, which was observed in our studies XRD patterns of nanoparticles showed the amorphous structure Downloaded by [Ondokuz Mayis Universitesine] at 16:45 12 November 2014 References [1] P Couvreur, C Dubernet, and F Puisieux, Controlled drug delivery with nanoparticles: Current possibilities and future trends, Eur J Pharm Biopharm 41 (1995), pp 2–13 [2] P Couvreur, Polyalkylcyanoacrylates as colloidal drug carriers, Crit Rev Ther Drug Carrier Syst (1988), pp 1–20 [3] J Kreuter, Nanoparticle – based drug delivery systems, J Controlled Release 16 (1991), pp 169–176 [4] K.S Soppimath, T.M Aminabhavi, A.R Kulkarni, and W.E Rudzinski, Biodegradable polymeric nanoparticles as drug delivery devices, J Controlled Release 70 (2001), pp 1–20 [5] E Allemann and R Gurny, Drug loaded nanoparticle-preparation methods and drug targeting issues, Eur J Pharm Biopharm 39 (1993), pp 173–191 [6] T Jung, W Kamm, A Breitenbach, E Kaiserling, J.X Xiao, and T Kissel, Biodegradable nanoparticle for oral delivery of peptides: Is there a role for polymers to affect mucosal uptake, Eur J Pharm Biopharm 50 (2000), pp 147–160 [7] K Bouchemal, S Briancon, E Perrier, H Fessi, I Bonnet, and N Zydowicz, Synthesis and characterization of polyurethane and poly(etherurethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification, Int J Pharm 269 (2004), pp 89–100 [8] M Kumar, Nano and microparticles as controlled drug delivery devices, J Pharm Sci (2000), pp 234–258 [9] N Kumar, M Ravikumar, and A.J Domb, Biodegradable block copolymers, Adv Drug Delivery Rev 53 (2001), pp 23–44 [10] J Brigger, C Dubernet, and P Couvreur, Nanoparticles in the cancer therapy and diagnosis, Adv Drug Delivery Rev 54 (2002), pp 631–651 [11] H.S Yoo, J.E Oh, K.H Lee, and T.G Park, Biodegadable nanoparticles containing PLGA conjugate for sustained release, Pharm Res 16 (1999), pp 1114–1118  ... nanoparticles by oil in water (O/W) emulsion solvent evaporation method We used acetone as solvent for polymer and water as non -solvent The purpose of this study is to use the emulsion solvent evaporation. .. concentration in the organic phase, PVA concentration in the aqueous phase and volume ratio of oil and water phases 2.3 Characterisation of nanoparticles We investigate the characterisation of nanoparticles, ... Universitesine] at 16:45 12 November 2014 2.2 Preparation of the drug nanoparticles In this study, nanoparticles are prepared by emulsification solvent evaporation method using sonication An organic