Skip to main content
SpringerLink
Log in

Flurbiprofen release from eudragit RS and RL aqueous nanosuspensions: a kinetic study by DSC and dialysis experiments

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The present work investigated the release of Flurbiprofen (FLU) from Eudragit RS100® (RS) and Eudragit RL100® (RL) nanosuspensions to a biological model membrane consisting of Dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV). This release was compared with those observed from solid drug particles as well as with dialysis experiments. Nanosuspensions were prepared by a modification of Quasi-Emulsion Solvent Diffusion technique. Drug release was monitored by the Differential Scanning Calorimetry (DSC). FLU dispersed in MLV affects the transition temperature (Tm) of DMPC liposomes, causing a shift towards lower values. The temperature shift is modulated by the drug fraction present in the aqueous lipid bilayer suspension. DSC was also performed, after increasing incubation periods at 37°C, on suspensions of blank liposomes added to fixed amounts of unloaded and FLU-loaded nanosuspensions, as well as to powdered free drug. Tm shifts, caused by the drug released from the polymeric system or by free-drug dissolution during incubation cycles, were compared with those caused by free drug increasing molar fractions dispersed directly in the membrane during their preparation. These results were compared with the drug release and were followed by a classical dialysis technique. Comparing the suitability of the 2 different techniques in order to follow the drug release as well as the differences between the 2 RL and RS polymer systems, it is possible to confirm the efficacy of DSC in studying the release from polymeric nanoparticulate systems compared with the “classical” release test by dialysis. The different rate of kinetic release could be due to void liposomes, which represent a better uptaking system than aqueous solution in dialysis experiments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. David S, Illum L, McVie JG, Tomlison E. Microspheres and Drug Therapy. Amsterdam, Netherlands: Elsevier; 1984.

    Google Scholar 

  2. Bakan JA, Powell TC, Szotak PS. Recent advances in microencapsulation of drugs to obtain reduced gastric irritation. In: Donbrow M, ed. Microcapsules and Nanoparticles in Medicine Pharmacy. Boca Raton, FL: CRC Press; 1991:183–192.

    Google Scholar 

  3. Kawata M, Nakamura M, Goto T, Ayoama T. Preparation and dissolution pattern of Eudragit RS microcapsules containing Ketoprofen. Chem Pharm Bull. 1968;34: 2618–2623.

    Google Scholar 

  4. Goto S, Kawata M, Makamura M, Maekauwa K, Ayoama T. Eudragit RS and RL (acrylic resins) micro-capsules as pH insensitive and sustained release preparations of ketoprofen. J Microencapsulation. 1986;3:293–304.

    Article  CAS  Google Scholar 

  5. Kawashima Y, Niwa T, Handa T, Takeuchi H, Iwamoto T, Ito Y. Preparation of prolonged-release spherical micromatrix of ibuprofen with acrylic polymer by the emulsion solvent diffusion method for improving bioavailability. Chem Pharm Bull. 1989;37:425–429.

    CAS  Google Scholar 

  6. Kawashima Y, Niwa T, Handa T, Takeuchi H, Ito Y. Preparation and characterization of a new controlled release ibuprofen suspension for improving suspendability. Int J Pharm. 1991;75:25–36.

    Article  CAS  Google Scholar 

  7. Kawashima Y, Toshiyuki H, Takeuchi H, Hino T, Ito Y. Control of prolonged drug release and compression properties of ibuprofen microsponges with acrylic polymer; Eudragit RS, changing their intrapartical porosity. Chem Pharm Bull. 1992;40:196–201.

    CAS  Google Scholar 

  8. Pignatello R, Vandelli MA, Giunchedi P, Puglisi G. Properties of Tolmetin-loaded Eudragit RL100 and RS100 microparticles prepared by different techniques. STP Pharma Sci. 1997;7:148–157.

    CAS  Google Scholar 

  9. Khalil E, Sallam A. Interaction of two Diclofenac acid salts with copolymers of ammoniomethacrylate: effect of additives and release profiles. Drug Dev Ind Pharmacy. 1999;25:419–427.

    Article  CAS  Google Scholar 

  10. Thaller VT, Kulshrestha MK, Bell K. The effect of pre-operative topical Flurbiprofen or Diclofenac on pupil dilatation. Eye. 2000;14:642–645.

    Google Scholar 

  11. Seydel JK. Nuclear magnetic resonance and differential scanning calorimetry as tools for studying drug-membrane interactions. Trends Pharmacol Sci. 1991;12:368–371.

    Article  CAS  Google Scholar 

  12. Duzgunes N, Wilschut J, Papahadjopoulos D. Control of membrane fusion by divalent cations, phospholipid headgroups and proteins. In: Conti F, Blumberg WE, De Gier J, Pocciari F, eds. Physical Methods on Biological Membranes and their Model Systems. New York, NY: Plenum Press; 1985:193–218.

    Google Scholar 

  13. Houslay MD, Stanley KK. Mobility of the lipid and protein components of biological membranes. In: Dynamics of Biological Membranes. New York, NY: Wiley and Sons; 1983:40–91.

    Google Scholar 

  14. Tenchov B. On the reversibility of the phase transitions in lipid-water systems. Chem Phys Lipids. 1991;57:165–177.

    Article  CAS  Google Scholar 

  15. Marsh D. Physical characterization of liposomes for understanding structure-function relationships in biological membranes. In: Barenholzand Y, Lasic DD, eds. Nonmedical Applications of Liposomes. Boca Raton, FL. CRC Press; 1996:1–16.

    Google Scholar 

  16. Mabrey-Gaud S. Differential scanning calorimetry of liposomes. In: Knight CG, ed. Liposomes: From Physical Structure to Therapeutic Applications. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press; 1981:105–138.

    Google Scholar 

  17. Bach D. Calorimetric studies of model and natural biomembranes. In: Chapman D, ed. Biomembrane Structure and Function. London, England: MacMillan Press; 1984:1–41.

    Google Scholar 

  18. Silvius JR. Thermotropic properties of phospholipid analogues. Chem Phys Lipids. 1991;57:241–252.

    Article  CAS  Google Scholar 

  19. Jain MK, Wu NM. Effect of small molecules on the Dipalmitoyllecithin liposomial bilayer: III Phase transition in lipid bilayer J Membrane Biol. 1977;34:151–201.

    Article  Google Scholar 

  20. Jain MK. Order and dynamics in bilayers. In: Jain MK, ed. Introduction to biological membranes. New York, NY: Wiley and Sons; 1988:122–165.

    Google Scholar 

  21. Castelli F, Puglisi G, Pignatello R, Gurrieri S. Calorimetric studies of the interaction of 4-Biphenylacetic acid and its β inclusion compound with lipid model membrane. Int J Pharm. 1989;52:115–121.

    Article  CAS  Google Scholar 

  22. Lohner K. Effects of small organic molecules on phospholipid phase transitions. Chem Phys Lipids. 1991;57:341–362.

    Article  CAS  Google Scholar 

  23. Raudino A, Castelli F. Modeling specific heat transient anomalies during permeation of liposomes by water-soluble substances. J Coll Interf Sci 1998;200:52–58.

    Article  CAS  Google Scholar 

  24. Castelli F, Conti B, Puglisi G, Conte U. Effect of molecular weight and storage times on Tolmetin release from poly-D,L-lactide microspheres to lipid model membrane: a calorimetric study. J Controlled Rel. 1996;40:277–284.

    Article  CAS  Google Scholar 

  25. Castelli F, Pitarresi G, Tomarchio V, Giammona G. Effect of pH on the transfer kinetics of an anti-inflammatory drug from polyaspartamide hydrogels to lipid model membrane. J Controlled Rel. 1997;45:103–111.

    Article  CAS  Google Scholar 

  26. Castelli F, Uccella N, Saija A, Trombetta D. Differences between Coumaric and Cinnamic acids in membrane permeation as evidenced by time-dependent calorimetry. J Agr Food Chem. 1999;47:991–995.

    Article  CAS  Google Scholar 

  27. Castelli F, Pitarresi G, Giammona G. Influence of different parameters on drug release from hydrogel systems to biomembrane model: evaluation by differential scanning calorimetry technique. Biomaterials. 2000;21:821–833.

    Article  CAS  Google Scholar 

  28. Pignatello R, Spedalieri G, Bucolo C, Maltese A, Puglisi G. Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials. 2002;15:3247–3255.

    Article  Google Scholar 

  29. Rouser G, Fleischer S, Yamamoto A. Two-dimensional thin-layer chromatographic separation of polar lipids and determination of phospholipids by phosphorous analysis of spots. Lipids. 1970;5:494–496.

    Article  CAS  Google Scholar 

  30. Jorgensen K, Ipsen JH, Mouritsen OG, Bennet D, Zuckermann MJ. The effects of density fluctuations on the partitioning of foreign molecules into bilayers: application to anaesthetics and insecticides. Biochim Biophys Acta. 1991;1062:227–238.

    Article  CAS  Google Scholar 

  31. Cevc G, Marsh D. Cell biology: a series of monographs, vol 5: phospholipid bilayers: physical principles and models, In: Bittar EE, ed. Phospholipid Bilayers Physical Principles and Models. New York, NY: Wiley; New York, 1987:1–441.

    Google Scholar 

  32. Pignatello R, Amico D, Chiechio S, Spadaro C, Giunchedi P, Puglisi G. Preparation and analgesic activity of Eudragit RS100® microparticles containing Diflunisal, Drug Delivery. 2001;8:35–45.

    Article  CAS  Google Scholar 

  33. Jenquin MR, McGinity JW. Characterization of acrylic resin matrix films and mechanisms of drugpolymer interactions. Int J Pharm. 1994;10:23–34.

    Article  Google Scholar 

  34. Pignatello R, Ferro M, Puglisi G. Preparation of solid dispersions of non-steroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions. PharmSciTech. In press.

  35. Jenquin MR, Liebowitz SM, Sarabia RE, McGinity JW. Physical and chemical factors influencing the release of drugs from acrylic resins films. J Pharm Sci. 1990;79:811–816.

    Article  CAS  Google Scholar 

  36. Castelli F, Messina C, Pignatello R, Puglisi G. Effect of pH on diclofenac release from Eudragit RS100® microparticles: a kinetic study by DSC. Drug Delivery. 2001;8:173–177.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria, 6, Città Universitaria, I-95125, Catania, Italy

    Francesco Castelli, Chiara Messina & Maria Grazia Sarpietro

  2. Dipartimento di Scienze Farmaceutiche, Università di Catania, Viale Andrea Doria, 6, Città Universitaria, I-95125, Catania, Italy

    Rosario Pignatello & Giovanni Puglisi

Authors
  1. Francesco Castelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Messina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Grazia Sarpietro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosario Pignatello
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giovanni Puglisi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesco Castelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Castelli, F., Messina, C., Sarpietro, M.G. et al. Flurbiprofen release from eudragit RS and RL aqueous nanosuspensions: a kinetic study by DSC and dialysis experiments. AAPS PharmSciTech 3, 9 (2002). https://doi.org/10.1208/pt030209

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/pt030209

Key words

Search

Navigation