Polymer Bulletin

, Volume 76, Issue 5, pp 2537–2558 | Cite as

Development of extended release loxoprofen sodium multiparticulates using different hydrophobic polymers

  • Muhammad Farooq
  • Muhammad Harris ShoaibEmail author
  • Rabia Ismail Yousuf
  • Faaiza Qazi
  • Muhammad Hanif
Original Paper


The objective of this study was to prepare sustained-release coated pellets of loxoprofen sodium by extrusion–spheronization technique and to assess the coating application of ethyl cellulose (10 cps), Eudragit RS100 and Eudragit RL100 on loxoprofen sodium core pellets by varying concentrations of polymeric coating. Coated pellets were evaluated for flow properties, friability, drug content and in vitro drug release in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8 and 7.4). Minimum drug release was found in an acidic medium which was sustained in a basic medium at a higher concentration of all three polymer coats of ethyl cellulose (15%), Eudragit RS100 (10%) and Eudragit RL100 (10%). Drug–excipient compatibility was determined by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) which showed the absence of any drug–excipient interaction. Results of image analysis and scanning electron microscopy (SEM) indicated the formation of smooth surface and spherical coated pellets. Drug release from these pellets was analyzed by using different kinetic models. Formulations F2, F4 and F5 followed first order (R2 = 0.91–0.98), while formulations F3, F6, F7 and F8 exhibited Higuchi release kinetics (R2 = 0.95–0.98). Non-Fickian diffusion (anomalous release) behavior was also observed by these formulations.


Extrusion–spheronization Eudragit RS100 Eudragit RL100 Ethyl cellulose Loxoprofen sodium Coated pellets 



Authors are thankful to Hilton Pharma Pakistan (Pvt.) Ltd. for providing active pharmaceutical ingredients.


  1. 1.
    Akhgari A, Tavakol A (2016) Prediction of optimum combination of Eudragit RS/Eudragit RL/ethyl cellulose polymeric free films based on experimental design for using as a coating system for sustained release theophylline pellets. Adv Pharm Bull 6(2):219–225CrossRefGoogle Scholar
  2. 2.
    Rajesh N (2010) Design and evaluation of controlled release of piroxicam from the pellets of microcrystalline cellulose and hydroxypropylmethyl cellulose blends. Int J Pharm Tech Res 2(2):1456–1473Google Scholar
  3. 3.
    Srisha V, Vijaaya Sri K, Devanna N, Suresh K (2013) Multiple unit extended release pellets of propranolol hydrochloride: preparation and characterization. Int J Pharm Pharm Sci 5(3):191–197Google Scholar
  4. 4.
    Muschert S, Siepmann F, Leclercq B, Carlin B, Siepmann J (2009) Prediction of drug release from ethylcellulose coated pellets. J Control Release 135(1):71–79CrossRefGoogle Scholar
  5. 5.
    Nasiri MI, Yousuf RI, Shoaib MH, Fayyaz M, Qazi F, Ahmed K (2016) Investigation on release of highly water soluble drug from matrix-coated pellets prepared by extrusion–spheronization technique. J Coat Technol Res 13(2):333–344CrossRefGoogle Scholar
  6. 6.
    Kilor VA, Sapkal NP, Awari JG, Shewale BD (2010) Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using κ-carrageenan as a pelletizing agent. AAPS Pharm Sci Tech 11(1):336–343CrossRefGoogle Scholar
  7. 7.
    Sawamura R, Kazui M, Kurihara A, Izumi T (2014) Absorption, distribution, metabolism and excretion of loxoprofen after dermal application of loxoprofen gel to rats. Xenobiotica 44(11):1026–1038CrossRefGoogle Scholar
  8. 8.
    Loya P, Kshatriya AA, Saraf MN (2011) Bioequivalence study of two brands of loxoprofen tablets in healthy volunteers. Int J Pharm Tech Res 3:2038–2046Google Scholar
  9. 9.
    Shoaib MH, Tazeen J, Merchant HA, Yousuf RI (2006) Evaluation of drug release kinetics from ibuprofen matrix tablets using HPMC. Pak J Pharm Sci 19(2):119–124Google Scholar
  10. 10.
    Qazi F, Shoaib MH, Yousuf RI, Nasiri MI, Ahmed K, Ahmad M (2017) Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent meclizine HCl. Lipids Health Dis 16(1):1–16CrossRefGoogle Scholar
  11. 11.
    Mehta RY, Missaghi S, Tiwari SB, Rajabi-Siahboomi ARJAP (2014) Application of ethylcellulose coating to hydrophilic matrices: a strategy to modulate drug release profile and reduce drug release variability. AAPS Pharm Sci Tech 15(5):1049–1059CrossRefGoogle Scholar
  12. 12.
    Godge G, Hiremath S (2015) Development and evaluation of colon targeted drug delivery system by using natural polysaccharides/polymers. Dhaka Univ J Pharm Sci 13(1):105–113CrossRefGoogle Scholar
  13. 13.
    Zaman M, Rasool S, Ali MY, Qureshi J, Adnan S, Hanif M, Sarfraz RM, Ijaz H, Mahmood A (2015) Fabrication and analysis of hydroxypropylmethyl cellulose and pectin based controlled release matrix tablets loaded with loxoprofen sodium. Adv Polym Technol 34(3):1–7CrossRefGoogle Scholar
  14. 14.
    Krogars K, Heinämäki J, Vesalahti J, Marvola M, Antikainen O, Yliruusi J (2000) Extrusion–spheronization of pH-sensitive polymeric matrix pellets for possible colonic drug delivery. Int J Pharm 199(2):187–194CrossRefGoogle Scholar
  15. 15.
    Venkatesan P, Manavalan R, Valliappan K (2011) Preparation and evaluation of sustained release loxoprofen loaded microspheres. J Basic Clin Pharm 2(3):159Google Scholar
  16. 16.
    Farooq M, Ahmad M, Madni A, Hanif M, Khan MR (2015) Development and evaluations of aceclofenac microcapsules for colon-targeted delivery: an in vitro study. Adv Polym Technol 34(2):1–8CrossRefGoogle Scholar
  17. 17.
    Srikanth B, Vemula C, Srinivas B, Sudheer K (2013) Nifedipine sustained release pellets formulation development and evaluation. Pharmascient 2(1):12–17Google Scholar
  18. 18.
    Abbaspour MR, Sadegi F, Garekani HA (2005) Preparation and characterization of ibuprofen pellets based on Eudragit RS PO and RL PO or their combination. Int J Pharm 303(1–2):88–94CrossRefGoogle Scholar
  19. 19.
    Khalid I, Ahmad M, Minhas MU, Barkat K (2018) Preparation and characterization of alginate-PVA-based semi-IPN: controlled release pH-responsive composites. Polym Bull 75:1–25CrossRefGoogle Scholar
  20. 20.
    Wu C, McGinity JW (2003) Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit RS PO hot-melt extrudates. Eur J Pharm Biopharm 56(1):95–100CrossRefGoogle Scholar
  21. 21.
    Pineda A, Hechenleitner A (2004) Characterization of ethylcellulose films containing natural polysaccharides by thermal analysis and FTIR spectroscopy. Acta Farm Bonaer 23(1):53–57Google Scholar
  22. 22.
    Khalid I, Ahmad M, Minhas MU, Barkat K (2018) Synthesis and evaluation of chondroitin sulfate based hydrogels of loxoprofen with adjustable properties as controlled release carriers. Carbohydr Polym 181:1169–1179CrossRefGoogle Scholar
  23. 23.
    Eissa MS, El-Sattar OIA (2016) Identification and structure elucidation of forced degradation products of the novel propionic acid derivative loxoprofen: development of stability-indicating chromatographic methods validated as per ICH guidelines. J Chromatogr Sci 55(4):417–428Google Scholar
  24. 24.
    Choi S-H, Kim S-Y, Ryoo JJ, Lee K-P (2001) Complexation of the non-steroidal anti-inflammatory drug loxoprofen with modified and unmodified β-Cyclodextrins. J Incl Phenom Macrocycl Chem 40(1):139–146CrossRefGoogle Scholar
  25. 25.
    Khalid I, Ahmad M, Usman Minhas M, Barkat K, Sohail M (2018) Cross-linked sodium alginate-g-poly (acrylic acid) structure: a potential hydrogel network for controlled delivery of loxoprofen sodium. Adv Polym Technol 37(4):985–995CrossRefGoogle Scholar
  26. 26.
    Ali F, Kumar R, Sahu PL, Singh GN (2017) Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients. J Therm Anal Calorim 130:1627–1641CrossRefGoogle Scholar
  27. 27.
    Liu Y, Sun Y, Sun J, Zhao N, Sun M, He Z (2012) Preparation and in vitro/in vivo evaluation of sustained-release venlafaxine hydrochloride pellets. Int J Pharm 426(1):21–28CrossRefGoogle Scholar
  28. 28.
    Siepmann F, Siepmann J, Walther M, MacRae R, Bodmeier R (2008) Polymer blends for controlled release coatings. J Control Release 125(1):1–15CrossRefGoogle Scholar
  29. 29.
    Abbas A, Abbaspour M, Moradkhanizadeh M (2013) Combination of pectin and Eudragit RS and Eudragit RL in the matrix of pellets prepared by extrusion–spheronization for possible colonic delivery of 5-amino salicylic acid. Jundishapur J Nat Pharm Prod 8(2):86–92Google Scholar
  30. 30.
    Strübing S, Metz H, Syrowatka F, Mäder K (2007) Monitoring of dissolution induced changes in film coat composition by 1H NMR spectroscopy and SEM. J Control Release 119(2):190–196CrossRefGoogle Scholar
  31. 31.
    Jain S, Shah S, Rajadhyaksha N, Singh P, Amin DP (2010) Once a day pellets of theophylline by extrusion spheronization technique using Gelucire matrix. Iran J Pharm Sci 6(4):235–243Google Scholar
  32. 32.
    Sriamornsak P, Nunthanid J, Luangtana-anan M, Puttipipatkhachorn S (2007) Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid. Eur J Pharm Biopharm 67(1):227–235CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Muhammad Farooq
    • 1
  • Muhammad Harris Shoaib
    • 1
    Email author
  • Rabia Ismail Yousuf
    • 1
  • Faaiza Qazi
    • 1
  • Muhammad Hanif
    • 2
  1. 1.Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical SciencesUniversity of KarachiKarachiPakistan
  2. 2.Department of Pharmacy, Faculty of PharmacyBahaudin Zakaria UniversityMultanPakistan

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