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JOURNALS || ASIO Journal of Pharmaceutical & Herbal Medicines Research (ASIO-JPHMR) [ISSN: 2455-281X]

Author Names : Bankim Chandra Nandy
Page No. : 25-40  volume 1 issue 1
Article Overview


Bankim Chandra Nandy, Bhaskar Mazumder. Optimization and Characterizations of Delayed Release Multi-Particulates System of Indomethacin: Screening of Formulations Variables and In Vitro Investigations, ASIO Journal of Pharmaceutical & Herbal Medicines Research (ASIO-JPHMR), 2015, 1(1): 25-40.


doi/dids No.: 12.2015-77737978

dids link:


The objectives of the present investigation were: (1) to elucidate the effect of formulation variables e.g., amount of Eudragit RS 100, concentration  of Tween 80 and agitation speed  on in-vitro release profiles of indomethacin from multi-particulates system, formulated with the combination of ethyl cellulose and Eudragit RS 100 by using a novel quasi emulsion solvent diffusion method; (2) to optimize the formulation variables by response surface methodology (RSM) ; and (3) to characterize the products on the basis of FTIR, thermal , particle size,  SEM, X-ray analyses and drug release kinetics studies. Experiments were designed and data was collected according to a three levels face centered central composite design. It was found that in-vitro release (Y1-Y3) were decreased significantly (p<0.05) with increase in amount of Eudragit RS 100 but increased significantly (p<0.05) with increase in surfactant concentration and stirring speed. The analysis of dissolution kinetics data showed that it followed Higuchi and zero-order model rather than first order model. It was observed that the drug release data of the selected formulation was close to the predicted release pattern. Therefore this approach suggested that the combination of Eudragit RS 100 and ethyl cellulose microspheres may be useful for the delivery of maximum amount of indomethacin in intact form to the colon.

Keywords: Indomethacin •  Eudragit RS100 •  Central composite-face centered designQuasi Emulsion Solvent Diffusion TechniqueMulti-particulates systemDelayed release colon targeted Delivery System

  1. Singhai SK, Singh VC, Nagar M , Gautam N, Trivedi P. Chronotherapy: A Novel Concept In Drug Delivery. Der Pharmacia Lettre, 2010; 2(3): 136-153.

  2. Loren L. Approaches to Nonsteroidal Anti-inflammatory Drug Use in the High-Risk Patient. Gastroenterology, 2001;120:594–606.  

  3. Khan MZI, Stedul HP, Kurjakovic N. A pH-dependent colon targeted oral drug delivery system using methacrylic acid co-polymers. II. Manipulation of drug release using Eudragit L100 and Eudragit S100 combinations. Drug Dev Ind Pharm. 2000; 26(5):549-554.

  4. Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. J Pharm Pharmaceut Sci. 2003; 6 (1): 33-66.

  5. Gazzaniga A, Iamartino P, Maffino G, Sangalli ME. Oral delayed release system for colonic specific drug delivery. International Journal of Pharmaceutics. 1994; 108: 77-83.

  6. Dey S,  Pramanik S,  Malgope A. Formulation and Optimization of Sustained Release Stavudine Microspheres Using Response Surface Methodology. ISRN Pharmaceutics, 2011, Article ID 627623:1- 7.

  7. Chourasia MK, Jain SK. Design and development of multiparticulate system for targeted drug delivery to colon. Drug Delivery, 2004; 11: 201–207.

  8.  Rao BS, Murthy KVR.Studies on rifampicin release from ethylcellulose coated nonpareil beads. International Journal of Pharmaceutics, 2002;231(1):97–106.

  9. Eudragit RS and Eudragit RL data sheets.Röhm Pharma GmbH, Darmstadt. 1991.

  10. Gupta BK, Pal R, Chakraborty M,Debnath R.Design, evaluation and optimization of microcapsules of leflunomide with Eudragit RS100 and Eudragit RL100 by solvent evaporation technique.Asian Journal of Pharmaceutics, 2009;3: 309–313.

  11. Kim  BK,Hwang SJ, Park JB, Park HJ. Preparation and characterization of drug-loaded poly methacrylate microspheres by an emulsion solvent evaporation method. J Microencapsul, 2002; 19: 811-822.

  12. Horoz BB, Kiliic M, Arslan N, Baykara YT. Effect of different dispersing agents on the characteristics of Eudragit microspheres prepared by a solvent evaporation method. J. Microencap. 2004; 21 (2): 191–202.

  13. Watts PJ, Davies MC, Melia CD. Encapsulation of 5 Aminisalicylic acid into Eudargit RS microspheres and modulation of their release characteristics by use of surfactants. Journal of   Controlled Release, 199;16:311-318.

  14. Lovrecich M, Nobile F, Rubessa F, Zingone G. Effect of ageing on the release of indomethacin from solid dispersions with Eudragits. International Journal of Pharmaceutics ,1996;131:247- 255.

  15.  Nokhodchi A, Javadzadeh Y, Siahi MR,Barzegar MJ. The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts. J. Pharm. Pharm. Sci. 2005;8 :18–25.

  16.  Lewis GA, Mathieu D, Phan RTL. Pharmaceutical Experimental Design. Marcel Dekker, New York, USA, 1961.

  17. Singh B, Agarwal R. Design development and optimization of controlled release microcapsules of dilitiazem hydrochloride.Indian Journal of Pharmaceutical Sciences, 2002; 64: 378–385.

  18.  Singh D, Saraf S, Dixit VK,Saraf S. Formulation optimization of gentamicin loaded eudragit RS100 microspheres using factorial design study. Biological & Pharmaceutical Bulletin, 2008;31: 662–667.

  19. Yang MS, Cui FD, You BG, Fan YL, Wang L, Yue P, Yang H. Preparation of sustained-release nitrendipine microspheres with Eudragit RS and Aerosil using quasi-emulsion solvent diffusion method. International Journal of Pharmaceutics, 2003; 259:103–113.

  20. Castelli F, Puglia C, Sarpietro MG,Rizza L, Bonina F. Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry. International Journal of Pharmaceutics, 2005;304:231–238.

  21.  Deore BV, Mahajan HS, Deore UV. Development and Characterization of sustained release microspheres by Quasi emulsion solvent diffusion method. Int, Jrnl. of ChemTech Res. 2009;1(3):634-642.

  22. Haznedar S, Dortunç B. Preparation and in vitro evaluation of Eudragit microspheres containing acetazolamide. International Journal of Pharmaceutics, 2004; 269:131–140.

  23.  The United States Pharmacopoeia. The National Formulary 24, The United States Pharmacopoeial Convention, Rockville, 1999.

  24. Oth MP, Moas AJ. Sustained release solid dispersions of indomethacin with Eudragit RS and RL. Int. J. Pharm. 1989;55:157- 164.

  25. Jain SK, Jain  A, Gupta Y, Ahirwar M. Design and Development of Hydrogel Beads for Targeted Drug Delivery to the Colon.AAPS PharmSciTech. 2007; 8 (3) 56:1-8.

  26. Khan MA, Anees AK, Agarwal V, Vaithiyalingam SR, Nazzal S, Reddy IK. Stability characterization of controlled release coprecipitates and solid dispersions. Journal of Controlled Release, 2000; 63: 1–6.

  27. Myers RH, Montgomery DC. Response Surface Methodology: Process and Product Optimization Using Designed Experiments. John Wiley & Sons, Inc, 2nd ed.  2002.

  28. Park SH, Kim HJ. A measure of slope-rotatability for second order response surface experimental designs. Journal of Applied Statistics, 1992;19: 391-404.

  29. Vaithiyalingam S, Khan MA. Optimization and characterization of controlled release multi-particulate beads formulated with a customized cellulose acetate butyrate dispersion. International Journal of Pharmaceutics, 2002; 234:179–193

  30. Higuchi T. Mechanism of sustained-action medication.Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 1963; 52 (12): 1145–1149.

  31.  Korsmeyer, RW,Gurny R, Doelker EM,Buri P,Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 1983; 15 (1): 25–35.

  32. Awe OO. How bad is Multicollinearity? Evidence from Multiple Linear Regression Analysis. Int J Cur Sci Res. 2012; 2(2): 344-349.