Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design


1 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

2 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Chemistry, Faculty of Basic Sciences, Golestan University, Gorgan, Iran


Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design.
Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates.
Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively.
Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained.


1. Jain A, Basarkar G, Upasani C. Developmental pharmaceutics for extended release pellets of aceclofenac. Int J Pharm Biotechnol 2011; 1:40-46.
2. Sadeghi F, Garekani HA, Goli F. Tableting of Eudragit RS and propranolol hydrochloride solid dispersion: effect of particle size, compaction force, and plasticizer addition on drug release. Drug Dev Ind Pharm 2004; 30:759-766.
3. Abbaspour M, Sadeghi F, Afrasiabi Garekani H. Thermal treating as a tool to produce plastic pellets based on Eudragit RS PO and RL PO aimed for tableting. Eur J Pharm Hiopharm 2007; 67:260-267.
4. Garekani HA, Nokhodchi A, Rayeni MA, Sadeghi F. Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration. Drug Dev Ind Pharm 2013; 39:1238-1246.
5. Kibria G, Roni MA, Absar MS, Jalil R-u. Effect of plasticizer on release kinetics of diclofenac sodium pellets coated with Eudragit RS 30 D. AAPS Pharm Sci Tech 2008; 9:1240-1246.
6. Mundada A, Satturwar P, Fulzele S, Joshi S, Dorle A. Characterization and evaluation of novel film forming polymer for drug delivery. Iran J Pharm Res 2011; 10:35.
7. Bando H, McGinity JW. Relationship between drug dissolution and leaching of plasticizer for pellets coated with an aqueous Eudragit S100:L100
dispersion. Int J Pharm 2006; 323:11-17.
8. Yang QW, Flament MP, Siepmann F, Busignies V, Leclerc B, Herry C, et al. Curing of aqueous polymeric film coatings: Importance of the coating level and type of plasticizer. Eur J Pharm Biopharm 2010; 74:362-370.
9. Kramar A, Turk S, Vrečer F. Statistical optimisation of diclofenac sustained release pellets coated with polymethacrylic films. Int J Pharm 2003; 256:43-52.
10. Bravo SA, Lamas MC, Salomón CJ. In-vitro studies of diclofenac sodium controlled-release from biopolymeric hydrophilic matrices. J Pharm Pharm Sci 2002; 5:213-219.
11. Thakhiew W, Devahastin S, Soponronnarit S. Effects of drying methods and plasticizer concentration on some physical and mechanical properties of edible chitosan films. J Food Eng 2010; 99:216-224.
12. Gendre C, Genty M, Silva JCd, Tfayli A, Boiret M, Lecoq O, et al. Comprehensive study of dynamic curing effect on tablet coating structure. Eur J Pharm Biopharm 2012; 81:657-665.
13. Bhattacharjya S, Wurster DE. Investigation of the drug release and surface morphological properties of film-coated pellets, and physical, thermal and mechanical properties of free films as a function of various curing conditions. AAPS Pharm Sci Tech 2008; 9:449-457.
14. Loveymi BD, Jelvehgari M, Zakeri-Milani P, Valizadeh H. Statistical optimization of oral vancomycin-eudragit RS nanoparticles using response surface methodology. Iran J Pharm Res 2012; 11:1001.
15. Wurster DE, Bhattacharjya S, Flanagan DR. Effect of curing on water diffusivities in acrylate free films as measured via a sorption technique. AAPS Pharm Sci Tech 2007; 8:E152-E157.