Home >Current Issue

Volume: 9, Issue: 7, July, 2019
DOI: 10.7324/JAPS.2019.90708

Research Article

Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release

Syaiful Choiri1, Teuku Nanda Saifullah Sulaiman2, Abdul Rohman3

  Author Affiliations


A novel of polymer combination promotes an increase of the ability for controlling the drug release. The objective of this research was to characterize the inter-polymer complexes (IPCs) of Eudragit (Eud) types (Eud RS, Eud L, or Eud E) and Kollidon SR (KSR), and elucidate their effects on the drug release kinetics and mechanism. Different preparation techniques were proposed using spray drying and ultrasonic-assisted anti-solvent techniques. The thermal activity, e.g., glass transition temperature (Tg) and Fourier transform infrared spectroscopy were used to characterize the molecular interaction of these IPCs. Theophylline (THP) was selected as a drug model. The effect on the drug release kinetics and mechanism was the main concern of this study. Depending on the results, the hydrogen bonding formation between polymers was observed by a shifting of OH and carbonyl group vibrations. In addition, the van der Waals interaction was identified by an alteration in the vibrational band around the 1,000–1,500 cm−1. Meanwhile, the change of physicochemical characteristic was identified by the Tg of IPCs. Eud E-KSR and Eud E-Eud L IPC were unable to control the THP release. Meanwhile, Eud L-KSR IPC and Eud RS-KSR IPC were success to control the THP release, but it was pH dependent and independent, respectively. This study concluded that the IPCs allowed the THP release in a controlled manner based on the IPC characteristics and their interactions. Either positive or negative interactions on the drug release were observed due to native characteristics of polymers.


Eudragit, Kollidon SR, inter-polymer complex, drug release.

Citation: Choiri S, Sulaiman TNS, Rohman A. Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release. J Appl Pharm Sci, 2019; 9(07):058–068.

Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Ainurofiq A, Choiri S. Development and optimization of a meloxicam/β-cyclodextrin complex for orally disintegrating tablet using statistical analysis. Pharm Dev Technol, 2018; 23:464–75; http://dx.doi.org/10.10 80/10837450.2016.1264418

Ainurofiq A, Choiri S. Drug release model and kinetics of natural polymers-based sustained release tablet. Lat Am J Pharm, 2015; 34:1328–37.

Ali R, Dashevsky A, Bodmeier R. Poly vinyl acetate and ammonio methacrylate copolymer as unconventional polymer blends increase the mechanical robustness of HPMC matrix tablets. Int J Pharm, 2017; 516:3–8; http://dx.doi.org/10.1016/j.ijpharm.2016.10.069

Al-Zoubi N, Al-obaidi G, Tashtoush B, Malamataris S. Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP. Drug Dev Ind Pharm, 2016; 42:270–9; http://dx.doi.org/10. 3109/03639045.2015.1047848

Borgquist P, Körner A, Piculell L, Larsson A, Axelsson A. A model for the drug release from a polymer matrix tablet—effects of swelling and dissolution. J Control Release, 2006; 113:216–25; http://dx.doi.org/10.1016/j. jconrel.2006.05.004

Brostow W, Chiu R, Kalogeras IM, Vassilikou-Dova A. Prediction of glass transition temperatures: binary blends and copolymers. Mater Lett, 2008; 62:3152–5; http://dx.doi.org/10.1016/j.matlet.2008.02.008

Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci, 2001; 13:123–33; http://dx.doi.org/10.1016/S0928-0987(01)00095-1

Elzayat EM, Abdel-Rahman AA, Ahmed SM, Alanazi FK, Habib WA, Sakr A. Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac. Pharm Dev Technol, 2017; 22:928–38; http://dx.doi.org/10.1080/1 0837450.2016.1212880

Gendre C, Genty M, Silva JC da, Tfayli A, Boiret M, Lecoq O, et al. Comprehensive study of dynamic curing effect on tablet coating structure. Eur J Pharm Biopharm, 2012; 81:657–65; http://dx.doi.org/10.1016/j. ejpb.2012.04.006

Gordon M, Taylor JS. Ideal copolymers and the second-order transitions of synthetic rubbers. i. non-crystalline copolymers. J Appl Chem, 1952; 2:493–500; http://dx.doi.org/10.1002/jctb.5010020901

Hauschild K, Picker-Freyer KM. Evaluation of tableting and tablet properties of Kollidon SR: the influence of moisture and mixtures with theophylline monohydrate. Pharm Dev Technol, 2006; 11:125–40; http://dx.doi.org/10.1080/10837450500464289

Hayashi T, Kanbe H, Okada M, Suzuki M, Ikeda Y, Onuki Y, Kaneko T, Sonobe T. Formulation study and drug release mechanism of a new theophylline sustained-release preparation. Int J Pharm, 2005; 304:91– 101; http://dx.doi.org/10.1016/j.ijpharm.2005.07.022

Hong Y, Liu G, Gu Z. Recent advances of starch-based excipients used in extended-release tablets: a review. Drug Deliv, 2016; 23:12–20; http://dx.doi.org/10.3109/10717544.2014.913324

Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release Off J Control Release Soc, 2001; 73:121–36.

Jeganathan B, Prakya V. Interpolyelectrolyte complexes of Eudragit® EPO with hypromellose acetate succinate and Eudragit® EPO with hypromellose phthalate as potential carriers for oral controlled drug delivery. AAPS PharmSciTech, 2015; 16:878–88; http://dx.doi.org/10.1208/s12249-014-0252-2

Khodaverdi E, Tekie FSM, Amoli SS, Sadeghi F. Comparison of plasticizer effect on thermo-responsive properties of Eudragit RS films. AAPS PharmSciTech, 2012; 13:1024–30; http://dx.doi.org/10.1208/s12249-012-9827-y

Khutoryanskaya OV, Morrison PWJ, Seilkhanov SK, Mussin MN, Ozhmukhametova EK, Rakhypbekov TK, Khutoryanskiy VV. Hydrogen-bonded complexes and blends of poly(acrylic acid) and methylcellulose: nanoparticles and mucoadhesive films for ocular delivery of riboflavin. Macromol Biosci, 2014; 14:225–34; http://dx.doi.org/10.1002/mabi.201300313

Khutoryanskiy VV. Hydrogen-bonded interpolymer complexes as materials for pharmaceutical applications. Int J Pharm, 2007; 334:15–26; http://dx.doi.org/10.1016/j.ijpharm.2007.01.037

Kubova K, Peček D, Hasserová K, Doležel P, Pavelková M, Vyslouzil J, Muselík J, Vetchy D. The influence of thermal treatment and type of insoluble poly(meth)acrylates on dissolution behavior of very soluble drug from hypromellose matrix tablets evaluated by multivariate data analysis. Pharm Dev Technol, 2017; 22:206–17; http://dx.doi.org/10.1080/1 0837450.2016.1193191

Lang B, Liu S, McGinity JW, III ROW. Effect of hydrophilic additives on the dissolution and pharmacokinetic properties of itraconazole-enteric polymer hot-melt extruded amorphous solid dispersions. Drug Dev Ind Pharm, 2016; 42:429–45; http://dx.doi.org/10.3109/03639045.2015.1075031

Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for Drug Delivery Systems. Annu Rev Chem Biomol Eng, 2010; 1:149–73; http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847

Makino S, Adachi M, Ohta K, Kihara N, Nakajima S, Nishima S, Fukuda T, Miyamoto T; Safety of Sustained-Release Theophylline and Injectable Methylxanthines Committee; Asthma Prevention and Management Guidelines Committee. A prospective survey on safety of sustained-release theophylline in treatment of asthma and COPD. Allergol Int, 2006; 55:395–402; http://dx.doi.org/10.2332/allergolint.55.395

Masina N, Choonara YE, Kumar P, du Toit LC, Govender M, Indermun S, Pillay V. A review of the chemical modification techniques of starch. Carbohydr Polym, 2017; 157:1226–36; http://dx.doi.org/10.1016/j. carbpol.2016.09.094

Merkle HP. Drug delivery’s quest for polymers: where are the frontiers? Eur J Pharm Biopharm, 2015; 97:293–303; http://dx.doi.org/10.1016/j. ejpb.2015.04.038

Moustafine RI, Bobyleva OV. Design of new polymer carriers based of Eudragit® E PO/Eudragit® L100-55 interpolyelectrolyte complexes using swellability measurements. J Control Release, 2006; 116:e35–6; http://dx.doi.org/10.1016/j.jconrel.2006.09.036

Moustafine RI, Bodrov AV, Kemenova VA, Rombaut P, Van den Mooter G. Drug release modification by interpolymer interaction between countercharged types of Eudragit® RL 30D and FS 30D in double-layer films. Int J Pharm, 2012; 439:17–21; http://dx.doi.org/10.1016/j. ijpharm.2012.09.044

Moustafine RI, Zaharov IM, Kemenova VA. Physicochemical characterization and drug release properties of Eudragit® E PO/Eudragit® L 100-55 interpolyelectrolyte complexes. Eur J Pharm Biopharm, 2006; 63:26–36; http://dx.doi.org/10.1016/j.ejpb.2005.10.005

Mustafin RI. Interpolymer combinations of chemically complementary grades of Eudragit copolymers: a new direction in the design of peroral solid dosage forms of drug delivery systems with controlled release (review). Pharm Chem J, 2011; 45:285; http://dx.doi.org/10.1007/s11094- 011-0618-7

Ohyagi N, Ueda K, Higashi K, Yamamoto K, Kawakami K, Moribe K. Synergetic role of hypromellose and methacrylic acid copolymer in the dissolution improvement of amorphous solid dispersions. J Pharm Sci, 2017; 106:1042–50; http://dx.doi.org/10.1016/j.xphs.2016.12.005

Park S-H, Chun M-K, Choi H-K. Preparation of an extended-release matrix tablet using chitosan/Carbopol interpolymer complex. Int J Pharm, 2008; 347:39–44; http://dx.doi.org/10.1016/j.ijpharm.2007.06.024

Patra ChN, Priya R, Swain S, Kumar Jena G, Panigrahi KC, Ghose D. Pharmaceutical significance of Eudragit: a review. Future J Pharm Sci, 2017; 3:33–45; http://dx.doi.org/10.1016/j.fjps.2017.02.001

Qiu Y, Lee PI. Rational design of oral modified-release drug delivery systems. Dev. Solid Oral Dos. Forms 2nd edition, Academic Press, Boston, MA, pp 519–54, 2017; http://dx.doi.org/10.1016/B978-0-12-802447- 8.00019-4

Riaz U, Ashraf SM. Characterization of polymer blends with FTIR spectroscopy. In: Thomas S, Grohens Y, Jyotishkumar P (eds.). Charact. Polym. Blends, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, pp 625–78, 2014; http://dx.doi.org/10.1002/9783527645602.ch20

Robertis SD, Bonferoni MC, Elviri L, Sandri G, Caramella C, Bettini R. Advances in oral controlled drug delivery: the role of drug– polymer and interpolymer non-covalent interactions. Expert Opin Drug Deliv, 2015; 12:441–53; http://dx.doi.org/10.1517/17425247.2015.966685

Saerens L, Dierickx L, Quinten T, Adriaensens P, Carleer vR, Vervaet C, Remon JP, De Beer T. In-line NIR spectroscopy for the understanding of polymer–drug interaction during pharmaceutical hot-melt extrusion. Eur J Pharm Biopharm, 2012; 81:230–7; http://dx.doi.org/10.1016/j. ejpb.2012.01.001

Siepmann J, Siepmann F. Modeling of diffusion controlled drug delivery. J Control Release, 2012; 161:351–62; http://dx.doi.org/10.1016/j. jconrel.2011.10.006

Terashima T, Sugita T, Sawamoto M. Single-chain crosslinked star polymers via intramolecular crosslinking of self-folding amphiphilic copolymers in water. Polym J, 2015; 47:667–77; http://dx.doi.org/10.1038/pj.2015.54

Thakral S, Thakral NK, Majumdar DK. Eudragit®: a technology evaluation. Expert Opin Drug Deliv, 2013; 10:131–49; http://dx.doi.org/10.1517 /17425247.2013.736962

Wood LA. Glass transition temperatures of copolymers. J Polym Sci, 1958; 28:319–30; http://dx.doi.org/10.1002/pol.1958.1202811707

Zayed M, Tourne-Peteilh C, Ramonda M, Rethore G, Weiss P, Martinez J, Subra G, Mehdi A, Devoisselle JM, Legrand P. Microgels of silylated HPMC as a multimodal system for drug co-encapsulation. Int J Pharm, 2017; 532:790–801; http://dx.doi.org/10.1016/j.ijpharm.2017.07.074

Zhang F, Lubach J, Na W, Momin S. Interpolymer complexation between Polyox and Carbopol, and its effect on drug release from matrix tablets. J Pharm Sci, 2016a; 105:2386–96; http://dx.doi.org/10.1016/j. xphs.2016.05.020

Zhang F, Meng F, Lubach J, Koleng J, Watson NA. Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants. Eur J Pharm Biopharm, 2016b; 105:97–105; http://dx.doi.org/10.1016/j.ejpb.2016.05.024

Zhang F, Meng F, Wang ZY, NA W. Interpolymer complexation between copovidone and carbopol and its effect on drug release from matrix tablets. Drug Dev Ind Pharm, 2017; 43:190–203; http://dx.doi.org/10.1080/0363 9045.2016.1230625

Zhu Y, Shah NH, Malick AW, Infeld MH, McGinity JW. Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate. Int J Pharm, 2002; 241:301–10; http://dx.doi.org/10.1016/S0378-5173(02)00244-2

Article Metrics

Similar Articles

Formulation design, in vitro evaluation and stability studies on mucoadhesive buccal films of anti-anginal calcium channel blocker
Bharath Kumar.V, Ashok kumar.A, Sudheer.B, Suresh Kumar.K, Srinivasa Rao.V, Kirtinidhi.K, Hitesh R Patel, Putta Rajesh Kumar

Formulation and comparison of in vitro release profile of hydrophilic and hydrophobic polymer based Naproxen matrix tablets
Kumar Bishwajit Sutradhar, Tajnin Ahmed, Afia Ferdous, Riaz Uddin

Synthesis and Characterization of biodegradable Poly (Vinyl caprolactam) grafted on to sodium alginate and its microgels for controlled release studies of an anticancer drug
K. Madhusudana Rao, K.S.V. Krishna Rao, P. Sudhakar, K. Chowdoji Rao and M.C.S. Subha