Evaluation of ethylcellulose and its pseudolatex (Surelease) in preparation of matrix pellets of theophylline using extrusion-spheronization

Document Type : Original Article

Authors

1 Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): This study evaluates the effect of substitution of microcrystalline cellulose (MCC) with ethylcellulose (EC) on mechanical and release characteristics of theophylline pellets.
Materials and Methods: The effect of addition of EC was investigated on characteristics of pellets with varying drug content prepared by extrusion-spheronization. Also the effect of type of granulating liquid (water or Surelease) was investigated on characteristics of selected pellets. The pellets were characterized for particle size (sieve analysis), mechanical strength, morphology (microscopy), thermal (DSC) and dissolution behaviors.
Results: The exrtudability of the wet mass was reduced upon inclusion of EC so that complete replacement of MCC was not possible. Increase in EC percentage led to lower production yield and formation of pellets with larger diameter and slightly rough surfaces. Inclusion of EC also affected the mechanical properties of pellets but had negligible effect on drug release profile. The surface of selected pellets became smoother and their production yield increased upon the use of Surelease as granulating liquid. In addition the rate of drug release decreased to some extent when Surelease was used.
Conclusion: Preparation of theophylline pellets with EC alone was not possible in process of extrusion-spheronization. Partial replacement of MCC with EC changed physicomechanical properties of pellets but hardly affected drug release. Although the use of Surelease as granulation liquid slightly decreased the rate of drug release, desirable matrix pellets with sustained drug release could not be produced. Despite this outcome however, these pellets could benefit from reduced coating thickness for drug release control.

Keywords

References

1.Koester M, Thommes M. New Insights into the Pelletization Mechanism by Extrusion/Spheroni-zation. AAPS PharmSciTech 2010; 11: 1549-1551.
2.Dukić-Ott A, Thommes M, Remon JP, Kleinebudde P, Vervaet C. Production of pellets via extrusion-spheronisation without the incorporation of microcrystalline cellulose: A critical review. Eur J Pharm Biopharm 2009; 71: 38-46.
3.Saripella KK, Loka NC, Mallipeddi R, Rane AM, Neau SH. A quality by experimental design approach to assess the effect of formulation and process variables on the extrusion and spheronization of drug-loaded pellets containing polyplasdone®XL-10. AAPS PharmSciTech 2015; pp 1-12. DOI: 10.1208/s12249-015-0345-6.
4.Wang J, Kan S, Chen T, Liu J. Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion–spheronization. Pharm Dev Technol 2015; 20: 246-256.
5.Sarkar S, Ang BE, Liew CV. Influence of starting material particle size on pellet surface roughness. AAPS PharmSciTech 2014a; 15: 131-139.
6.Schrank S, Hodzic A, Zimmer A, Glasser BJ, Khinast J, Roblegg E. Ibuprofen-loaded calcium stearate pellets: Drying-induced variations in dosage form. AAPS PharmSciTech 2012; 13: 686-698.
7.Santos H, Veiga F, Pina Ma E, Sousa JJ. Compaction, compression and drug release properties of diclofenac sodium and ibuprofen pellets comprising xanthan gum as a sustained release agent. Int J Pharm 2005; 295: 15-27.
8.Chopra R, Alderborn G, Podczeck F, Newton JM. The influence of pellet shape and surface properties on the drug release from uncoated and coated pellets. Int J Pharm 2002; 239: 171-178.
9.Charoenthai N, Kleinebudde P, Puttipipatkhachom S, Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose. AAPS Pharm SciTech 2007; 8: E99-E109.
10.Santos H, Veiga F, Pina M, Podczeck F, Sousa J. Physical properties of chitosan pellets produced by extrusion spheronisation: influence of formulation variables. Int J Pharm 2002; 246: 153-169.
11.Tho I, Kleinebudde P, Sande SA. Extrusion/ spheronization of pectin-based formulations. I. Screening of important factors. AAPS PharmSciTech 2001; 2: 54-62.
12.Tho I, Kleinebudde P, Sande SA. Extrusion/ spheronization of pectin-based formulations. II. Effect of additive concentration in the granulation liquid. AAPS PharmSciTech 2001; 2: 63-72.
13.Sriamornsak P, Nunthanid J, Luangtana-anan M, Weerapol Y, Puttipipatkhachorn S. Alginate-based pellets prepared by extrusion/spheronization: Effect of the amount and type of sodium alginate and calcium salts. Eur J Pharm Biopharm 2008; 69: 274-284.
14.Sriamornsak P, Nunthanid J, Luangtana-anan M, Puttipipatkhachorn S. Alginate-based pellets prepared by extrusion/spheronization: A preliminary study on the effect of additive in granulating liquid. Eur J Pharm Biopharm 2007; 67: 227-235.
15.Chatlapalli R, Rohera BD. Physical characteriza-tion of HPMC and HEC and investigation of their use as pelletization aids. Int J Pharm 1998; 161: 179-193.
16.Cornelia Krueger C,  Thommes M. Multiple batch manufacturing of theophylline pellets using the wet-extrusion spheronization process with κ-carrageenan as pelletisation aid. Pharm Dev Technol 2013; 18: 225-235.
17.Sadeghi F, Hijazi H, Afrasiabi Garekani H. Production of of Ibuprofen Pellets Containing High Amount of Rate Retarding Eudragit RL Using PEG400 and Investigation of Their Physicomecha-nical Properties. Iran J Basic Med Sci 2011; 14: 383-390.
18.Abbaspour MR, 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 Biopharm 2007; 67: 260–267.
19.Abbaspour MR, Sadeghi F, Afrasiabi Garekani H. Preparation and characterization of ibuprofen pellets based on Eudragit RS PO and RL PO or their combination. Int J Pharm 2005; 303: 88-94.
20.Villa Nova M, Gonçalves MdCP, Nogueira AC, Herculano LdS, Medina AN, Bazotte RB, Bruschi ML. Formulation and characterization of ethylcellulose microparticles containing. l-alanyl-l-glutamine peptide. Drug Dev Ind Pharm 2014; 40: 1308-1317.
21.Santos JV, Pina MET, Marques MPM, de Carvalho LAB, New sustained release of Zidovudine Matrix tablets− cytotoxicity toward Caco-2 cells. Drug Dev Ind Pharm 2013; 39: 1154-1166.
22.Nguyen C, Christensen JM, Ayres JW. Verapamil sustained release: New formulation and convolution. Pharm Dev Technol. 2012; 17: 148-157.
23.Sanchez-Lafuente C, Faucci MT, Fernández-Arévalo M, Álvarez-Fuentes J, Rabasco AM, Mura P. Development of sustained release matrix tablets of didanosine containing methacrylic and ethylcellulose polymers. Int J Pharm 2002; 234: 213-221.
24.Sadeghi F, Ford JL, Rajabi-Siahboomi A. The influence of drug type on the release profiles from Surelease-coated pellets. Int J Pharm 2003; 254: 123-135.
25.Reyes G, Deng H, Rajabi-Siahboomi A. 2008. Application of ethylcellulose in preparation of extended release theophylline inert matrix tablets by wet granulation. AAPS annual meeting and exposition. 2008
26.Zhang Y, Huang Z, Omari-Siaw E, Lu S, Zhu Y, Jiang D, Wang M, Yu J, Xu X. Preparation and in-vitro in-vivo evaluation of sustained release matrix pellets of capsaicin to enhance the oral bioavailability. AAPS PharmSciTech 2015; 20: 1-11.
27.Siddique S, Khanam J, Bigoniya P. Development of sustained release capsules containing “coated matrix granules of metoprolol tartrate” AAPS Pharm SciTech 2010; 11: 1306-1314.
28.Verhoeven E, De Beer TR, Van den Mooter G, Remon JP, Vervaet C. Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion. Eur J Pharm Biopharm 2008; 69: 312-319.
29.Kojima M, Nakagami H. Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers. J Control Release 2002; 82: 335-343.
30.Hamedelniel EI, Bajdik J, Pintye-Hódi K.  Optimization of preparation of matrix pellets containing ethylcellulose. Chem Eng Process 2010; 49: 120–124.
31.Chi N, Guo JH, Zhang Y, Zhang W, Xing Tang X. An oral controlled release system for amroxol hydrochloride containing a wax and a water insoluble polymer. Pharm Dev Technol 2010; 15: 97-104.
32.Mallipeddi R, Saripella KK, Neau SH. Use of coarse ethylcellulose and PEO in beads produced by extrusion – spheronization. Int J Pharm 2010; 385: 53-65.
33.Mallipeddi R, Saripella KK, Neau SH. Use of fine particle ethylcellulose as the diluent in the production of pellets by extrusion-spheronization. Saudi Pharm J 2014; 22: 360-372.
34.Afrasiabi Garekani H, Faghihnia Torshizi M, Sadeghi F. Surelease as granulating liquid in preparation of sustained release matrices of ethylcellulose and theophylline. Drug Dev Ind Pharm 2015; 41: 1655-1660.
35.Lustig-Gustafsson C, Kaur Johal H, Podczeck F, Newton JM. The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronisation. Eur J Pharm Sci 1999; 8: 147-152.
36.Sousa JJ, Sousa A, Podczeck F, Newton JM. Factors influencing the physical characteristics of pellets obtained by extrusion-spheronization. Int J Pharm 2002; 232: 91-106.
37.Sarkar S, Liew CV. Moistening liquid-dependent de-aggregation of microcrystalline cellulsoe and its impact on pellet formation by extrusion-spheronization. AAPS PharmSciTech. 2014; 15: 753-761.
38.Mascia S, Seiler C, Fitzpatrick S, Wilson DI. Extrusion-spheronisation of microcrystalline cellulose pastes using a non-aqueous liquid binder. Int J Pharm 2010; 389: 1-9.
39.Crowley MM, Schroeder B, Fredersdorf A, Obara S, Talarico M, Kucera S, McGinity JW. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int J Pharm 2004; 269: 509-522.
40.Zhang G, Schwartz JB, Schnaare RL, Wigent RJ, Sugita ET. Bead coating: II. Effect of spheronization technique on drug release from coated spheres. Drug Dev Ind Pharm 1991 17, 817-830.
41.Steckel H, Mindermann-Nogly F. Production of chitosan pellets by extrusion/spheronization. Eur J Pharm Biopharm 2004; 57: 107–114.
42.Türk C, Hasçiçek C, Gönül N. 2009. Evaluation of drug-polymer interaction in polymeric micro-spheres containing diltiazem hydrochloride. J Therm Anal Calorim 2009; 95: 865-869.
43.Goskonda SR, Hileman GA,  Upadrashta SM. Controlled release pellets by extrusion-spheronization. Int J Pharm. 1994; 111: 89-97.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 1
January 2017
Pages 9-16

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