Abstract
In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology, total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio of TEC.
Similar content being viewed by others
REFERENCES
Abdul S, Chandewar AV, Jaiswal SB. A flexible technology for modified-release drugs: multiple-unit pellet system (MUPS). J Control Release. 2010;147:2–16.
Shamma RN, Basalious EB, Shoukri RA. Development and optimization of a multiple-unit controlled release formulation of a freely water soluble drug for once-daily administration. Int J Pharm. 2011;405:102–12.
Ye Z, Rombout P, Remon JP, Vervaet C, Mooter GV. Correlation between the permeability of metoprolol tartrate through plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films and drug release from reservoir pellets. Eur J Pharm Biopharm. 2007;67:485–90.
Andreani L, Cercena R, Ramos BGZ, Soldi V. Development and characterization of wheat gluten microspheres for use in a controlled release system. Mat Sci and Eng C. 2009;29:524–31.
Mateovic T, Kriznar B, Bogataj M, Mrhar A. The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres. J Microencapsul. 2002;19:29–36.
Nordstierna L, Abdalla AA, Nordin M, Nyden M. Comparison of release behaviour from microcapsules and microspheres. Progress in Org Coat. 2010;69:49–51.
Kangarlou S, Haririan I, Gholipour Y. Physico-mechanical analysis of freeethylcellulose films comprised with novel plasticizers of vitamin resources. Int J Pharm. 2008;356:153–66.
Lai HL, Pitt K, Craig DQM. Characterization of the thermal properties of ethylcellulose using differential scanning and quasi-isothermal calorimetric approaches. Int J Pharm. 2010;386:178–84.
Sogol K, Ismaeil H. Mechanical influence of static versus dynamic loadings on parametrical analysis of plasticized ethyl cellulose films. Int J Pharm. 2011;408:1–8.
Şengel CT, Hasçiçek C, Gönül N. Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride. J Microencapsul. 2006;23:135–52.
Grattard N, Pernin M, Marty B, Roudaut G, Champion D, Meste ML. Study of release kinetics of small and high molecular weight substances dispersed into spray-dried ethylcellulose microspheres. J Control Release. 2002;84:125–35.
Hamedelniel EI, Bajdik J, Sovány T, Pintye-Hódi K. Delayed release matrix pellet preparation containing an alkalizing pore-former agent. Chem Eng Res Des. 2011. doi:10.1016/j.cherd.2010.12.003.
Schaefer MJ, Singh J. Effect of isopropyl myristic acid ester on the physical characteristics and in vitro release of etoposide from PLGA microspheres. AAPS PharmSciTech. 2000;1:Article 32.
Schilling SU, Shah NH, Malick AW, McGinity JW. Properties of melt extruded enteric matrix pellets. Eur J Pharm Biopharm. 2010;74:352–61.
Gutiérrez-Rocca J, McGinity JW. Influence of water soluble and insoluble plasticizers on the physical and mechanical properties of acrylic resin copolymers. Int J Pharm. 1994;103:293–301.
DiNunzio JC, Brough C, Miller DA, Williams III RO, McGinity JW. Applications of KinetiSol® dispersing for the production of plasticizer free amorphous solid dispersions. Eur J Pharm Sci. 2010;40:179–87.
Fadda HM, Khanna M, Santos JC, Osman D, Gaisford S, Basit AW. The use of dynamic mechnanical analysis (DMA) to evaluate plasticizztion of acrylic polymer films under simulated gastrointestinal conditions. Eur J Pharm Biopharm. 2010;76:493–7.
Vieira MGA, Silva MA, Santos LO, Beppu MM. Natural-based plasticizers and biopolymer films: a review. Eur Polym J. 2011;47:254–63.
Kojima M, Nakagami H. Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers. J Control Release. 2002;82:335–43.
Lin WJ, Lee HK, Wang DM. The influence of plasticizers on the release of theophylline from microporous-controlled tablets. J Control Release. 2004;99:415–21.
Meier MM, Kanis LA, Soldi V. Characterization and drug-permeation profiles of microporous and dense cellulose acetate membranes: influence of plasticizer and pore forming agent. Int J Pharm. 2004;278:99–110.
Siepmann J, Lecomte F, Bodmeir R. Diffusion-controlled drug delivery systems: calculation of the required composition to achieve desired release profiles. J Control Release. 1999;60:379–89.
Tarvainen M, Sutinen R, Peltonen S, Mikkonen H, Maunus J, Vähä-Heikkilä K, et al. Enhanced film-forming properties for ethylcellulose and starch acetate using n-alkenyl succinic anhydrides as novel plasticizers. Eur J Pharm Sci. 2003;19:363–71.
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;74:362–70.
Sant S, Nadeau V, Hildgen P. Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles. J Control Release. 2005;107:203–14.
Emeje MO, Kunle OO, Ofoefule SI. Compaction characteristics of ethylcellulose in the presence of some channeling agents: technical note. AAPS PharmSciTech. 2006;7:Article 58.
Wu C, McGinity JW. Influence of ibuprofen as a solid-state plasticizer in Eudragit RS 30 D on the physicochemical properties of coated beads. AAPS PharmSciTech. 2001;2:Article 24.
Zhu Y, Shah NH, Malick AW, Infeld MH, McGinity JW. Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethylcitrate. Int J Pharm. 2002;241:301–10.
Şengel-Türk CT, Hasçiçek C, Gönül N. Microspheres-based once-daily modified release matrix tablets for oral administration in angina pectoris. J Microencapsul. 2008;25:257–66.
Türk CT, Hasçiçek C, Gönül N. Evaluation of drug-polymer interaction in polymeric microspheres containing diltiazem hydrochloride. J Therm Anal Cal. 2009;95:865–9.
USP 30/NF 25. Diltiazem hydrochloride. In: United States of Pharmacopoeia 30/National Formula 25. Rockville, USA: 2007. p. 1952–6.
Chow AHL, Ho SSS, Tong HHY, Ma HHM. Parameters affecting in-liquid drying microencapsulation and release rate of cefaclor. Int J Pharm. 1998;172:113–25.
Oh E, Luner PE. Surface free energy of ethylcellulose films and the influence of plasticizers. Int J Pharm. 1999;188:203–19.
ACKNOWLEDGMENTS
The authors would like to thank TUBITAK (The Scientific and Technical Research Council of Turkey) and the Management of Scientific Research Projects of Ankara University (project number: 2003.08.03.038) for their financial support of this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sengel-Turk, C.T., Hascicek, C. & Gonul, N. Ethylcellulose-Based Matrix-Type Microspheres: Influence of Plasticizer RATIO as Pore-Forming Agent. AAPS PharmSciTech 12, 1127–1135 (2011). https://doi.org/10.1208/s12249-011-9680-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-011-9680-4