AAPS PharmSciTech

, Volume 10, Issue 2, pp 335–345 | Cite as

Agglomerates Containing Pantoprazole Microparticles: Modulating the Drug Release

  • Renata P. Raffin
  • Paolo Colombo
  • Fabio Sonvico
  • Alessandra Rossi
  • Denise S. Jornada
  • Adriana R. Pohlmann
  • Silvia S. Guterres
Research Article

Abstract

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5–79.0%), drug loading (58–101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm−2), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.

Key words

agglomerates delayed release gastro-resistance microparticles 

Notes

ACKNOWLEDGEMENT

The authors are grateful for the financial support of CNPq/MCT, Universal 2007 CNPq and for the CAPES fellowship. The financial support of the Italian Ministry for University and Research is also gratefully acknowledged. We thank Prof. Edilson Benvenutti for the BET analysis.

REFERENCES

  1. 1.
    N. S. Barakat, and A. A. E. Ahmad. Diclofenac sodium loaded-cellulose acetate butyrate: Effect of processing variables on microparticles properties, drug release kinetics and ulcerogenic activity. J. Microencapsul. 25(1):31–45 (2008).PubMedCrossRefGoogle Scholar
  2. 2.
    Y. C. Huang, A. Vieira, M. K. Yeh, and C. H. Chiang. Containing betamethasone pulmonary anti-inflammatory effects of chitosan microparticles. J. Bioact. Compat. Polym. 22:30–41 (2007).CrossRefGoogle Scholar
  3. 3.
    S. Tamilvanan and B. Sa. In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of ibuprofen. AAPS PharmSciTech. 7(3):Article 72 (2006).Google Scholar
  4. 4.
    K. P. R. Chowdary and Y. Srinivasa Rao. Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: A technical note. AAPS PharmSciTech. 4(3):Article 39 (2003).Google Scholar
  5. 5.
    K. Masters. The spray drying handbook, Longman, New York, 1991.Google Scholar
  6. 6.
    R. C. R. Beck, A. R. Pohlmann, and S. S. Guterres. Nanoparticle-coated microparticles: preparation and characterization. J. Microencapsul. 21:499–512 (2004).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Goula, K. Adamopoulos, and N. Kazakis. Influence of spray drying conditions on tomato powder properties. Dry. Technol. 22(5):1129–1151 (2004).CrossRefGoogle Scholar
  8. 8.
    M. I. Ré. Microencapsulation by spray drying. Dry. Technol. 16:1195–1236 (1998).CrossRefGoogle Scholar
  9. 9.
    R. P. Raffin, S. S. Guterres, A. R. Pohlmann, and M. I. Ré. Powder characteristics of pantoprazole delivery systems produced in different spray-dryer scales. Dry. Technol. 24:339–348 (2006).CrossRefGoogle Scholar
  10. 10.
    R. P. Raffin, D. S. Jornada, M. I. Ré, A. R. Pohlmann, and S. S. Guterres. Sodium Pantoprazole-loaded enteric microparticles prepared by spray drying: effect of the scale of production and process validation. Int. J. Pharm. 324:10–18 (2006).PubMedCrossRefGoogle Scholar
  11. 11.
    C.G. Oster, and T. Kissel. Comparative study of DNA encapsulation into PLGA microparticles using modified double emulsion methods and spray drying techniques. J. Microencapsul. 22:235–244 (2005).PubMedCrossRefGoogle Scholar
  12. 12.
    R. P. Raffin, L. M. Colomé, S. E. Haas, D. S. Jornada, A. R. Pohlmann, and S. S. Guterres. Development of HPMC and Eudragit S100® blended microparticles containing sodium pantoprazole. Pharmazie. 62:361–364 (2007).PubMedGoogle Scholar
  13. 13.
    S. Harikarnpakdee, V. Lipipun, N. Sutanthavibul, and G. C. Ritthidej. Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer. AAPS PharmSciTech. 7(1):Article 12 (2006).Google Scholar
  14. 14.
    P. Russo, F. Buttini, F. Sonvico, R. Bettini, G. Massimo, C. Sacchetti, P. Colombo, and P. Santi. Chimeral agglomerates of microparticles for administration of caffeine nasal powders. J. Drug Deliv. Sci. Technol. 14:449–454 (2004).Google Scholar
  15. 15.
    T. D. Reynolds, S. A. Mitchell, and K. M. Balwinsky. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets. Drug Dev. Ind. Pharm. 28:457–466 (2002).PubMedCrossRefGoogle Scholar
  16. 16.
    E. Esposito, F. Cervellati, E. Menegatti, C. Nastruzzi, and R. Cortesi. Spray dried Eudragit microparticles as encapsulation devices for vitamin C. Int. J. Pharm. 242:329–334 (2002).PubMedCrossRefGoogle Scholar
  17. 17.
    G. F. Palmieri, G. Bonacucina, P. Di Martino, and S. Martelli. Gastro-resistant microspheres containing ketoprofen. J. Microencapsul. 19:111–119 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    D. B. Beten, M. Gelbcke, B. Diallo, and A. J. Moes. Interaction between dipyridamole and Eudragit S. Int. J. Pharm. 88:31–37 (1992).CrossRefGoogle Scholar
  19. 19.
    H. P. de Oliveiraa, J. J. F. Albuquerque Jr., C. Nogueirasa, and J. Rieumonta. Physical chemistry behavior of enteric polymer in drug release systems. Int. J. Pharm. 366:185–189 (2009).CrossRefGoogle Scholar
  20. 20.
    S. Cheer, A. Prakash, D. Faulds, and H. Lamb. Pantoprazole—an update of its pharmacological properties and therapeutic use in the management of acid-related disorders. Drugs. 63:101–132 (2003).PubMedCrossRefGoogle Scholar
  21. 21.
    B. K. Kim, S. J. Hwang, J. B. Park, and H. J. Park. Characteristics of felodipine-located poly(ɛ-caprolactone) microspheres. J. Microencapsul. 22:193–203 (2005).PubMedCrossRefGoogle Scholar
  22. 22.
    Y. J. Fu, F. L. Mi, T. B. Wong, and S. S. Shyu. Characteristic and controlled release of anticancer drug loaded poly (D,L-lactide) microparticles prepared by spray drying technique. J. Microencapsul. 18:733–747 (2001).PubMedCrossRefGoogle Scholar
  23. 23.
    S. Tsantilis, and S. E. Pratsinis. Soft- and hard-agglomerate aerosols made at high temperatures. Langmuir. 20:5933–5939 (2004).PubMedCrossRefGoogle Scholar
  24. 24.
    R. Boerefijn, Z. Ning, and M. Ghadiri. Disintegration of weak lactose agglomerates for inhalation applications. Int. J. Pharm. 172:199–209 (1998).CrossRefGoogle Scholar
  25. 25.
    P. Russo, C. Sacchetti, I. Pasquali, R. Bettini, G. Massimo, P. Colombo, and A. Rossi. Primary microparticles and agglomerates of morphine for nasal insufflation. J. Pharm. Sci. 95:2553–2561 (2006).PubMedCrossRefGoogle Scholar
  26. 26.
    R. Moreno-Atanasio, and M. Ghadiri. Mechanistic analysis and computer simulation of impact breakage of agglomerates: Effect of surface energy. Chem. Eng. Sci. 61:2476–2481 (2006).CrossRefGoogle Scholar
  27. 27.
    Stability testing guideline RE 1, Brazilian National Health Surveillance Agency, July 29, 2005.Google Scholar
  28. 28.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Stability Testing of New Drug Substances and Products (Q 1A (R2)), 2003.Google Scholar
  29. 29.
    R. P. Raffin, L. M. Colomé, S. S. Guterres, and A. R. Pohlmann. Validation of analytical methodology by HPLC for quantification and stability evaluation of sodium pantoprazole. Quim. Nova. 30:1001–1005 (2007).Google Scholar
  30. 30.
    S. Brunauer, P. H. Emmet, and E. Teller. Adsorption of gases in multimolecular layers. J. Am. Chem. Soc. 60:309–319 (1938).CrossRefGoogle Scholar
  31. 31.
    Y. S. L. Lee, R. Poynter, F. Podczeck, and J. M. Newton. Development of a Dual Approach to Assess Powder Flow from Avalanching Behavior. AAPS PharmSciTech 1(3):Article 21 (2000).Google Scholar
  32. 32.
    European Pharmacopoeia. 5th edn., Council of Europe, Strasbourg, 2005.Google Scholar
  33. 33.
    US Pharmacopeia XXX, US Pharmacopeial Convention, Rockville, MD, 2007.Google Scholar
  34. 34.
    Farmacopéia Brasileira 4a ed., Atheneu, São Paulo, 2005.Google Scholar
  35. 35.
    H. X. Guo, J. Heinamaki, and J. Yliruusi. Amylopectin as a subcoating material improves the acidic resistance of enteric-coated pellets containing a freely soluble drug. Int. J. Pharm. 235:79–86 (2002).PubMedCrossRefGoogle Scholar
  36. 36.
    R. P. Raffin, L. M. Colomé, A. R. Pohlmann, and S. S. Guterres. Preparation, characterization, and in vivo anti-ulcer evaluation of pantoprazole-loaded microparticles. Eur. J. Pharm. Biopharm. 63:198–204 (2006).PubMedCrossRefGoogle Scholar
  37. 37.
    R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, and N. A. Peppas. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 15:25–35 (1983).CrossRefGoogle Scholar
  38. 38.
    Z. Wong, and E. Schaffer. Experimental study of contact line dynamics by capillary rise and fall. In K. L. Mittal (ed.), Contact Angle, Wettability and Adhesion, Brill, Boston, 2003, pp. 25–37.Google Scholar
  39. 39.
    K. N. Atuah, E. Walter, H. P. Merkle, and H. O. Alpar. Encapsulation of plasmid DNA in PLGA-stearylamine microspheres: a comparison of solvent evaporation and spray-drying methods. J. Microencapsul. 20:387–399 (2003).PubMedCrossRefGoogle Scholar
  40. 40.
    R. P. Raffin, P. Colombo, F. Sonvico, F. S. Polleto, G. Colombo, A. Rossi, A. R. Pohlmann, and S. S. Guterres. Soft Agglomerates of pantoprazole gastro-resistant microparticles for oral administration and intestinal release. J. Drug Deliv. Sci. Technol. 17:407–413 (2007).Google Scholar
  41. 41.
    P. Costa, and J. M. S. Lobo. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci. 13:123–133 (2001).PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Renata P. Raffin
    • 1
  • Paolo Colombo
    • 2
  • Fabio Sonvico
    • 2
  • Alessandra Rossi
    • 2
  • Denise S. Jornada
    • 1
  • Adriana R. Pohlmann
    • 1
    • 3
  • Silvia S. Guterres
    • 1
  1. 1.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Dipartimento FarmaceuticoUniversità degli Studi di ParmaParmaItaly
  3. 3.Departamento de Química Orgânica, Instituto de QuímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

Personalised recommendations