Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2002 June; 3(2): 35–45.
Published online 2002 March 20. doi:  10.1208/pt030210
PMCID: PMC2750312

Preparation of solid dispersions of nonsteroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions


This work studied the mechanisms of interaction between Eudragit RS100 (RS) and RL100 (RL) polymers with 3 nonsteroidal anti-inflammatory drugs: diflunisal (DIF), flurbiprofen (FLU), and piroxicam (PIR). Solid dispersions of polymers and drugs at different weight ratios were prepared by coevaporation of their ethanol solutions. The resulting coevaporates were characterized in the solid state (Fourier-transformed infrared spectroscopy (FT-IR) IR, differential scanning calorimetry, powder-x-ray diffractometry) as well as by studying the in vitro drug release in a gastroenteric environment. Absorption tests from drug solutions to the solid polymers were also performed to better explain the mechanism of interactions between them. The preparative conditions did not induce changes in the crystalline state of the drugs (amorphization or polymorphic change). Drugs strongly interacted with the ammonium groups present in polymers, giving an electrostatic interaction that reinforced the mere physical dispersion of drug molecules within polymer networks. Such interactions are related to the chemical structure of the drugs and to their dissociated or undissociated state. The dispersion of drugs in the polymer matrices strongly influenced their dissolution rate, which appeared slower and more gradual than those of the pure drugs, when polymer ratios were increased. RL coevaporates usually displayed higher dissolution rates. The kinetic evaluation of the dissolution profile, however, suggested that both the drug solubility in the external medium and its diffusion capacity within the polymer network are involved. In the sorption experiments, RL showed a greater adsorptive capacity than RS, in relation to the greater number of quaternary ammonium functions, which behave as activity sites for the electrostatic interactions. In the presence of Tris-HCl buffer (pH 7.4), drug adsorption was reduced, as a consequence of the competition of the chloride ions with drug anions for the polymer binding sites. In general, DIF and FLU displayed a similar interaction with RS and RL active sites; PIR's was different. The different molecular structures of these agents can justify such findings. The presence of a carboxyl group (instead of another dissociable acidic moiety, like the hydroxy-enolic one in the PIR molecule) could help explain the strong interaction with RS and RL polymers' quaternary ammonium centers. Preliminary studies like ours are important in helping develop better forecasting and increasing the understanding of the incorporation/release behavior of drugs from particulate delivery systems that can be made from these polymers.

Key Words: Eudragit RS100, Eudragit RL100, diflunisal, flurbiprofen, piroxicam, solid dispersions, coevaporates

Full Text

The Full Text of this article is available as a PDF (740K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Goto S, Kawata M, Nakamura M, Maekauwa K, Ayoama T. Eudragit RS and RL (acrylic resins) micro-capsules as pH insensitive and sustained release preparations of ketoprofens. J Microencapsul. 1986;3:293–304. doi: 10.3109/02652048609021799. [PubMed] [Cross Ref]
2. Kawata M, Nakamura M, Goto T, Ayoama T. Preparation and dissolution pattern of Eudragit RS microcapsules containing ketoprofen. Chem Pharm Bull. 1986;34:2618–2623. [PubMed]
3. Kawashima Y, Iwamoto T, Niwa T, Takeuchi H, Hino T. Size control of ibuprofen microspheres with an acrylic polymer by changing the pH in an aqueous dispersion medium and its mechanisms. Chem Pharm Bull. 1993;41:191–195.
4. Murthy T, Verma P. Controlled transdermal delivery of flurbiprofen films using mixed grades of Eudragit: design, in-vitro and in-vivo evaluation. Int J Pharm Adv. 1996;1:391–397. [PubMed]
5. Pignatello R, Spedalieri G, Bucolo C, Maltese A, Puglisi G. Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials. 2002;15:3247–55. doi: 10.1016/S0142-9612(02)00080-7. [PubMed] [Cross Ref]
6. Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G. Eudragit RS100® nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci. 2002;16:53–61. doi: 10.1016/S0928-0987(02)00057-X. [PubMed] [Cross Ref]
7. Benita S, Hoffman A, Donbrow M. Microencapsulation of paracetamol using polyacrylate resins (Eudragit Retard): kinetics of drug release and evaluation of kinetic model. J Pharm Pharmacol. 1985;37:391–395. [PubMed]
8. Beten DB, Moës AJ. Controlled-release coevaporates of dipyridamole prepared with acrylic polymers. Int J Pharm. 1994;103:243–251. doi: 10.1016/0378-5173(94)90174-0. [Cross Ref]
9. Jenquin MR, McGinity JW. Characterization of acrylic resin matrix films and mechanisms of drug-polymer interactions. Int J Pharm. 1994;10:23–34. doi: 10.1016/0378-5173(94)90072-8. [Cross Ref]
10. Lin SY, Cheng CL, Perng RI. Solid state interaction studies of drug-polymers: II. Warfarin-Eudragit E, RL or S resins. Eur J Pharm Sci. 1994;1:313–322. doi: 10.1016/0928-0987(94)90040-X. [Cross Ref]
11. Jenquin MR, Liebowitz SM, Sarabia RE, McGinity JW. Physical and chemical factors influencing the release of drugs from acrylic resin films. J Pharm Sci. 1990;79:811–816. doi: 10.1002/jps.2600790914. [PubMed] [Cross Ref]
12. Oth MP, Moës AJ. Sustained release solid dispersions of indomethacin with Eudragit RS and RL. Int J Pharm. 1989;55:157–164. doi: 10.1016/0378-5173(89)90037-9. [Cross Ref]
13. Kislalioglu MS, Khan MA, Blount C, Goettsh RW, Bolton S. Physical characterisation and dissolution properties of ibuprofen-Eudragit coprecipitates. J Pharm Sci. 1991;80:799–804. doi: 10.1002/jps.2600800820. [PubMed] [Cross Ref]
14. Pignatello R, Vandelli MA, Giunchedi P, Puglisi G. Properties of tolmetin-loaded Eudragit RL100 and RS100 microparticles prepared by different techniques. S.T.P. Pharma Sciences. 1997;7:148–157.
15. Heun G, Lambov N, Groning R. Experimental and molecular modelling studies on interactions between drugs and Eudragit RL/RS resins in aqueous environment. Pharm Acta Helv. 1998;73:57–62. doi: 10.1016/S0031-6865(97)00053-8. [Cross Ref]
16. Pignatello R, Ferro M, De Guidi G, et al. Preparation, characterisation and photosensitivity studies of solid dispersions of diflunisal and Eudragit RS100® and RL100® Int J Pharm. 2001;218:27–42. doi: 10.1016/S0378-5173(01)00597-X. [PubMed] [Cross Ref]
17. Pignatello R, Consoli P, Puglisi G. In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles. J Microencapsul. 2000;17:373–383. doi: 10.1080/026520400288337. [PubMed] [Cross Ref]
18. Vrecer F, Srcic S, Šmid-Korbar J. Investigation of piroxicam polymorphism. Int J Pharm. 1991;68:35–41. doi: 10.1016/0378-5173(91)90124-7. [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists