Skip to main content
SpringerLink
Log in

Osmotic flow through asymmetric membrane: A means for controlled delivery of drugs with varying solubility

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

A nondisintegrating, controlled release, asymmetric membrane capsular system of flurbiprofen was developed and evaluated for controlled release of the drug to overcome some of its side effects. Asymmetric membrane capsules were prepared using fabricated glass mold pins by phase inversion process. The effect of different formulation variables was studied based on 23 factorial design; namely, level of osmogen, membrane thickness, and level of pore former. Effects of polymer diffusibility and varying osmotic pressure on drug release were also studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. Differential scanning calorimetry studies showed no incompatibility between the drug and the excipients used in the study. In vitro release studies for all the prepared formulations were done (n=6). Statistical test (Dunnett multiple comparison test) was applied for in vitro drug release atP>.05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 92.94. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed the Higuchi model and the mechanism of release was Fickian diffusion.

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. Santus G, Baker RW. Osmotic drug delivery: a review of the patent literature.J Control Release. 1995;35:1–21.

    Article  CAS  Google Scholar 

  2. Theeuwes F. Elementary osmotic pump.J Pharm Sci. 1975;64: 1987–1991.

    Article  CAS  PubMed  Google Scholar 

  3. Theeuwes F, Saunders RJ, Mefford WS, inventors. Process for forming outlet passageways in pills using a laser. US parent 4 088 864. May 9, 1978.

  4. Herbig SM, Cardinal JR, Korsmeyer RW, Smith KL. Asymmetric membrane tablet coatings for osmotic drug delivery.J Control Release. 1995;35:127–136.

    Article  CAS  Google Scholar 

  5. Thombre AG, Cardinal JR, DeNoto AR, Gibbes DC. Asymmetric membrane capsules for osmotic drug delivery. II. In vitro and in vivo drug release performance.J Control Release. 1999;57:65–73.

    Article  CAS  PubMed  Google Scholar 

  6. Thombre AG, Cardinal JR, DeNoto AR, Herbig SM, Smith KL. Asymmetric membrane capsules for osmotic drug delivery. I. Development of a manufacturing process.J Control Release. 1999;57:55–64.

    Article  CAS  PubMed  Google Scholar 

  7. Lin YK, Ho HO. Investigations on the drug releasing mechanism from an asymmetric membrane-coated capsule with an in situ formed delivery orifice.J Control Release. 2003;89:57–69.

    Article  CAS  PubMed  Google Scholar 

  8. Marsh CC, Schuna AA, Sundstorm WR. A review of selected investigational nonsteroidal antiinflammatory drugs of the 1980s.Pharmacotherapy. 1986;6:10–25.

    Article  CAS  PubMed  Google Scholar 

  9. Gilman AG, Rall TW, Taylor P.Goodman and Gillman’s The Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press; 1990.

    Google Scholar 

  10. British Medical Association and Royal Pharmaceutical Society of Great Britain.British National Formulary 45. London, UK: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2003.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  12. Chandran C, Roy A, Saha RN. Flurbiprofen: a review.Indian J Pharm Educ. 2005;39:22–26.

    Google Scholar 

  13. McClelland GA, Sutton SC, Engle K, Zentner GM. Solubility modulated osmotic pump: in vitro/in vivo release of diltiazem hydrochloride.Pharm Res. 1991;8:88–92.

    Article  CAS  PubMed  Google Scholar 

  14. Zentner GM, McClelland GA, Sutton SC. Controlled porosity solubility and resin modulated osmotic drug delivery systems for release of diltiazem hydrochloride.J Control Release. 1991;16:237–244.

    Article  CAS  Google Scholar 

  15. Martin A.Physical Pharmacy. New Delhi, India, B. I. Waverly Pvt Ltd; 1999.

    Google Scholar 

  16. Rawlins EA.Bentley’s Textbook of Pharmaceutics. London, UK: Bailliere Tindall 2004.

    Google Scholar 

  17. Bennett PN, Brown MJ.Clinical Pharmacology. London, UK: Churchill Livingstone; 2004.

    Google Scholar 

  18. Chien YW.Novel Drug Delivery Systems. New York NY: Marcel Dekker Inc; 1992.

    Google Scholar 

  19. Najib N, Suleiman M. The kinetics of drug release from ethyl cellulose solid dispersions.Drug Dev Ind Pharm. 1985;11: 2169–2181.

    Article  CAS  Google Scholar 

  20. Desai SJ, Singh P, Simonelli AP, Higuchi WI. Investigation of factors influencing release of solid drug dispersed in wax matrices. III. Quantitative studies involving polyethylene plastic matrix.J Pharm Sci. 1966;55:1230–1234.

    Article  CAS  PubMed  Google Scholar 

  21. Higuchi T. Mechanism of sustained action medication, theoretical analysis of rate of release of solid drugs dispersed in solid matrices.J Pharm Sci. 1963;52:1145–1149.

    Article  CAS  PubMed  Google Scholar 

  22. Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation: I—theoretical consideration.Ind Eng Chem. 1931;23:923–931.

    Article  CAS  Google Scholar 

  23. Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers.Int J Pharm. 1983;15:25–35.

    Article  CAS  Google Scholar 

  24. Avdeef A. pH-metric solubility 1: solubility pH profiles from bjerrum plots. Gibbs buffer and pKa in solid state.Pharmacy and Pharmacology Communications. 1998;4:165–178.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Rajiv Academy for Pharmacy, Delhi-Mathura Bye Pass, NH# 2, 286001, Mathura, Uttar Pradesh, India

    Anil K. Philip & Kamla Pathak

Authors
  1. Anil K. Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamla Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anil K. Philip.

Additional information

Published: July 7, 2006

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Philip, A.K., Pathak, K. Osmotic flow through asymmetric membrane: A means for controlled delivery of drugs with varying solubility. AAPS PharmSciTech 7, 56 (2006). https://doi.org/10.1208/pt070356

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/pt070356

Keywords

Search

Navigation