Effect of Particle Size, Compaction Force and Presence of Aerosil 200 on the Properties of Matrices Prepared from Physical Mixture of Propranolol Hydrochloride and Eudragit RS or RL

Document Type: Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Research Center, Mashhad University of Medical sciences, Mashhad, Iran

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

Abstract

Objective
Eudragits are widely used polymers in the production of oral sustained release dosage forms. The application of these polymers in the production of inert insoluble matrices has been investigated. However the effect of particle size, compaction force and presence of Aerosil 200 as a glidant on the properties of Eudragit RS and RL matrices prepared by direct compression of their physical mixtures with drug have not been fully investigated. This study was performed in order to investigate the effect of above mentioned factors on physicomechanical and release properties of propranolol hydrochloride and Eudragit RS or RL matrices.
Materials and Methods
Polymers were separated to different size fractions using series of sieves. Matrices were prepared in 1:3 ratio by direct compression of physical mixture of drug and polymer. To study the effect of Aerosil 200, matrices were prepared from different size fractions containing 1%w/w Aerosil 200. To investigate the effect of compaction force, the 125-177µm size fraction of polymer was chosen and compression carried out at 5, 10, 15, 20 and 30 kN compaction force. Matrices were characterized for their hardness and dissolution.
Results
The results showed that due to decrease in tablet hardness the release rate increased with increase in polymer particle size. Drug release rates were almost the same for both polymers at similar particle size range. The same trend was also observed for matrices containing Aerosil 200. Addition of Aerosil 200 decreased the rate of drug release from all matrices except those prepared from 250-350 µm size fraction. This was attributed to increase in the tablet hardness. Increase in compaction force from 5kN to 20kN increased the tablet hardness and consequently decreased the release rate, however, further increase in compaction force from 20 to 30 kN did not significantly affect the release rates of drug.
Conclusion
Polymer particle size, presence of Aerosil and compaction force are important factors affecting drug release from Eudragit RS or RL matrices. Eudragit RS and RL polymers alone are not suitable for preparation of sustained release matrices containing water soluble drugs.

Keywords


1.Zheng W, Sauer D, McGinity J.Influence of hydroxyethylcellulose on the drug release properties of theophylline pellets coated with Eudragit® RS 30 D. Eur J Pharm Biopharm  2005; 59:147-154.

2. Pignatello R, Ferro M, De Guidi G, Salemi G, Vandelli M A, Guccione S, et al. Preparation, Characterization and photosensitivity studies of solid dispersions of diflunisal and Eudragit RS100 and RL100. Inter J Pharma 2001; 218: 27-42.

3. Sadeghi F, Afrasiabi Garekani H, Goli F. Tableting of Eudragit RS and propranolol hydrochloride solid dispersion: effect of particle size, compaction force, and plasitcizer addition on drug release. Drug Develop and Indust Pharm  2004; 30: 759-766.

4.Aceres JM, Cruz, R, Hernandez E. preparation and characterization of furosemide – Eudragit controlled release systems. I  J pharm  2000; 195: 45 – 53.

5.Azarmi S, Farid J, Nokhodchi A, Bahari-Saravi S M, Valizadeh H. Thermal treating as a tool for sustained release of indomethacin from Eudragit RS and RL matrices. Inter J Pharm 2002; 246 171-177.

6. Kaul D, Venkatarum S. Sustained release tablet formulation for a new iron chelator. Drug Develop and Industl Pharm 1992; 18: 1023-1035.

7.Ceballos A, Cirri M, Maestrelli F, Corti G, Mura P. Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets .I J Farm 2005, 60: 913-918.

 8.Jenquin MR, McGinity JW. Characterization of acrylic resin matrix films and mechanisms of drug polymer interactions. Inter J Pharm 1994; 101: 23-34.

9.Effentakis M, Buckton G. Modeling drug release from hydrophobic matrices by use of thermodynamic activation parameters. Inter J Pharm 1990; 60: 229-234.

10. Fassihi A, Parker M, Pourkavoos N. Solid dispersion controlled release: effect of particle size, compression force and temperature. Drug Develop and Indust Pharm 1985; 11: 523-535.

11. Katikaneni PR, Upadrashta SM, Neau SH, Mitra AK. Ethylcellulose matrix controlled release tablets of a water soluble drug. Interl J Pharm 1995; 123: 119-125.

12. Dabbagh  MA, Ford  JL, Rubinstein M H, Hogan  JE. Effect of polymer particle size, compaction pressure and hydrophilic polymers on drug release from matrices containing ethylcellulose. Inter J Pharm 1996; 140: 85-95.

13. Cameron  CG, McGinity  JW. Controlled release theophylline tablet formulations containing acrylic resins: II. Combination resin formulations. Drug Develop and Indust Pharm1987; 13: 1409-1427.

14. Collet J, Moreton C. Modified-release peroral dosage forms. In: Aulton M E. (2nd Ed).  Pharmaceutics. The Science of Dosage Form Design: Churchill Livingstone; 2002. p. 298.

15. Chang RK, Leonzio M, Hussain MA. Effect of colloidal silicon dioxide on flowing and tableting experimental crosslinked polyalkylammonium polymer. Pharm Deve Tech 1999; 4: 285-289.

16. Stamm A, Tritsch  JC. Some consideration on the liberation of drug from inert matrices. Drug Develop and Indust Pharm 1986, 12: 2337-2353.

17. Sarisuta N, Mahahpunt P. Effect of compression force and type of fillers on release of diclofenac sodium from matrix tablets. Drug Develop and Indust Pharm 1994; 20: 1049-1061.