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Lipospheres as Carriers for Topical Delivery of Aceclofenac: Preparation, Characterization and In Vivo Evaluation

AAPS PharmSciTech volume 9, pages 154–162 (2008)Cite this article

Abstract

The purpose of this study was to prepare lipospheres containing aceclofenac intended for topical skin delivery with the aim of exploiting the favorable properties of this carrier system and developing a sustained release formula to overcome the side effects resulting from aceclofenac oral administration. Lipospheres were prepared using different lipid cores and phospholipid coats adopting melt and solvent techniques. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis, DSC, In vitro drug release and storage study. The anti-inflammatory effect of liposphere systems was assessed by the rat paw edema technique and compared to the marketed product. Results revealed that liposphere systems were able to entrap aceclofenac at very high levels (93.1%). The particle size of liposphere systems was well suited for topical drug delivery. DSC revealed the molecular dispersion of aceclofenac when incorporated in lipospheres. Both entrapment efficiency and release were affected by the technique of preparation, core and coat types, core to coat ratio and drug loading. Lipospheres were very stable after 3 months storage at 2–8°C manifested by low leakage rate (less than 7%) and no major changes in particle size. Finally, liposphere systems were found to possess superior anti-inflammatory activity compared to the marketed product in both lotion and paste consistencies. Liposphere systems proved to be a promising topical system for the delivery of aceclofenac as they possessed the ability to entrap the drug at very high levels and high stability, and to sustain the anti-inflammatory effect of the drug.

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References

  1. H. Bunjes, and M. H. J. Koch. Saturated phospholipids promote crystallization but slow down polymorphic transitions in triglyceride nanoparticles. J. Control. Release. 107:229–243 (2005).

    Article  CAS  Google Scholar 

  2. R. Valjakka-Koskela, M. Kirjavainen, J. Monkkonen, A. Urtti, and J. Kiesvaara. Enhancement of percutaneous absorption of naproxen by phospholipids. Int. J. Pharm. 175:225–230 (1998).

    Article  CAS  Google Scholar 

  3. E. B. Souto, S. A. Wissing, C. M. Barbosa, and R. H. Muller. Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery. Int. J. Pharm. 278:71–77 (2004).

    Article  CAS  Google Scholar 

  4. A. J. Domb, L. Bergelson, and S. Amselem. Lipospheres for controlled delivery of substances. Microencapsulation, methods and industrial applications, Marcel Dekker, New York, NY, 1996, pp. 377–410.

    Google Scholar 

  5. P. A. Insel. Analgesic-antipyretics and anti-inflammatory agents: drugs employed in the treatment of rheumatoid arthritis and gout. In L. S. Goodman, A. Gilman, T. W. Rall, A. S. Nies, and P. Taylor (eds.), The pharmacological basis of therapeutics, McGraw-Hill International editions, New York, NY, 1992, pp. 638–681.

    Google Scholar 

  6. A. Domb and M. Maniar, Inventors. Liposphere delivery systems for local anesthetics. US patent 5 227 165. July 13, 1993.

  7. D. B. Masters and A. J. Domb. Liposphere local anesthetic timed-release for perineural site application. Pharm. Res. 15:1038–1045 (1998).

    Article  CAS  Google Scholar 

  8. V. Iannuccelli, N. Sala, R. Tursilli, G. Coppi, and S. Scalia. Influence of liposphere preparation on butyl-methoxydibenzoyl methane photostability. Eur. J. Pharm. Biopharm. 63:140–145 (2006).

    Article  CAS  Google Scholar 

  9. R. Tursilli, A. Casolari, V. Iannuccelli, and S. Scalia. Enhancement of melatonin photostability by encapsulation in lipospheres. J. Pharm. Biomed. Anal. 40:910–914 (2006).

    Article  CAS  Google Scholar 

  10. I. El Gibaly, and S. K. Abdel-Ghaffar. Effect of hexacosanol on the characteristics of novel sustained release allopurinol solid lipospheres (SLS): factorial design application and product evaluation. Int. J. Pharm. 294:33–51 (2005).

    Article  Google Scholar 

  11. S. Toongsuwan, L. Li, B. K. Erickson, and H. Chang. Formulation and characterization of bupivacaine lipospheres. Int. J. Pharm. 280:57–65 (2004).

    Article  CAS  Google Scholar 

  12. R. R. Habashy, A. B. Abdel-Naim, A. E. Khalifa, and M. M. Al-Azizi. Anti-inflammatory effects of jojoba liquid wax in experimental models. Pharmacol. Res. 51:95–105 (2005).

    Article  Google Scholar 

  13. Z. Mei, H. Chen, T. Weng, Y. Yang, and X. Yang. Solid lipid nanoparticles and microemulsion for topical delivery of triptolide. Eur. J. Pharm. Biopharm. 56:189–196 (2003).

    Article  CAS  Google Scholar 

  14. H. Reithmeier, J. Herrmann, and A. Gopferich. Development and characterization of lipid microparticles as a drug carrier for somatostatin. Int. J. Pharm. 218:133–143 (2001).

    Article  CAS  Google Scholar 

  15. M. Maniar, D. Hannibal, S. Amselem, X. Xie, R. Burch, and A. Domb. Characterization of Lipospheres ™-1: Effect of carrier and phospholipid on the loading of drug into the lipospheres. Pharm. Res. 8 suppl.:S–185 (1991).

    Google Scholar 

  16. N. S. Barakat, and A. E. B. Yassin. In vitro characterization of carbamazepine-loaded precifac lipospheres. Drug Delivery 13:95–104 (2006).

    Article  CAS  Google Scholar 

  17. R. Cortesi, E. Esposito, G. Luca, and C. Nastruzzi. Production of lipospheres as carriers for bioactive compounds. Biomaterials 23:2283–2294 (2002).

    Article  CAS  Google Scholar 

  18. R. M. Abra, P. J. Mihalko, and H. Schreier. The effect of lipid composition upon the encapsulation and in vitro leakage of metaproterenol sulfate from 0.2 µm diameter, extruded, multilamellar liposomes. J. Control. Release. 14:71–78 (1990).

    Article  CAS  Google Scholar 

  19. T. Nii, and F. Ishii. Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int. J. Pharm. 298:198–205 (2005).

    Article  CAS  Google Scholar 

  20. B. D. Kim, K. Na, and H. K. Choi. Preparation and characterization of solid lipid nanoparticles (SLN) made of cacao butter and curdlan. Eur. J. Pharm. Sci. 24:199–205 (2005).

    Article  CAS  Google Scholar 

  21. E. Escribano, A. C. Calpena, J. Queralt, R. Obach, and J. Domenech. Assessment of diclofenac permeation with different formulations: anti-inflammatory study of a selected formula. Eur. J. Pharm Sci. 19:203–210 (2003).

    Article  CAS  Google Scholar 

  22. Y. Iscan, S. Hekimoglu, M. F. Sargon, and A. A. Hincal. Deet-loaded solid lipid particles for skin delivery: In vitro release and skin permeation characteristics in different vehicles. J. Microencapsul. 23:315–327 (2006).

    Article  CAS  Google Scholar 

  23. T. Bekerman, J. Golenser, and A. Domb. Cyclosporin nanoparticulate lipospheres for oral administration. J. Pharm. Sci. 93:1264–1270 (2004).

    Article  CAS  Google Scholar 

  24. Hou, C. Xie, K. Huang, and C. Zhu. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials 24:1781–1785 (2003).

    Article  CAS  Google Scholar 

  25. S. Budavari, M. J. O’Neil, A. Smith, P. E. Heckelman, J. F. Kinneary (eds.) The Merck Index, an Encyclopedia of Chemicals, Drugs and Biologicals. Whitehouse station, NJ, Merck and Co., 1996.

  26. S. Scalia, R. Tursilli, N. Sala, and V. Iannuccelli. Encapsulation in lipospheres of the complex between butyl methoxydibenzoylmethane and hydroxypropyl-ß-cyclodextrin. Int. J. Pharm. 320:79–85 (2006).

    Article  CAS  Google Scholar 

  27. B. Vora, A. J. Khopade, and N. K. Jain. Proniosome based transdermal delivery of levonorgesterol for effective contraception. J. Control. Release. 54:149–165 (1998).

    Article  CAS  Google Scholar 

  28. H. Schreier, M. Levy, and P. Mihalko. Sustained release of liposome-encapsulated gentamycin and fate of phospholipid following intramuscular injection in mice. J. Control. Release. 5:187–192 (1987).

    Article  CAS  Google Scholar 

  29. A. Lippacher, R. H. Muller, and K. Mader. Preparation of semisolid drug carriers for topical application based on solid lipid nanoparticles. Int. J. Pharm. 214:9–12 (2001).

    Article  CAS  Google Scholar 

  30. H. Robson, D. Q. M. Craig, and D. Deutsch. An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres II. The effects of buffer composition on drug release. Int. J. Pharm. 195:137–145 (2000).

    Article  CAS  Google Scholar 

  31. R. H. Muller, M. Radtke, and S. A. Wissing. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev. 54:S131–S155 (2002).

    Article  CAS  Google Scholar 

  32. S. A. Wissing, O. Kayser, and R. H. Muller. Solid lipid nanoparticles for parentral drug delivery. Adv. Drug Deliv. Rev. 56:1257–1272 (2004).

    Article  CAS  Google Scholar 

  33. A. Lippacher, R. H. Muller, and K. Mader. Semisolid SLN™ dispersions for topical application influence of formulation and production parameters on viscoelastic properties. Eur. J. Pharm. Biopharm. 53:155–160 (2002).

    Article  CAS  Google Scholar 

  34. E. B. Souto, R. H. Muller, and S. Gohla. A novel approach based on lipid nanoparticles (SLN®) for topical delivery of a-lipoic acid. J. Microencapsul. 22:581–592 (2005).

    Article  CAS  Google Scholar 

  35. A. Bhatia, R. Kumar, and O. P. Katare. Tamoxifen in topical liposomes: development, characterization and in-vitro evaluation. J. Pharm. Pharmaceut. Sci. 7:252–259 (2004).

    CAS  Google Scholar 

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Affiliations

  1. Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Maha Nasr, Samar Mansour, Nahed D. Mortada & A. A. El Shamy

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  1. Maha Nasr
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  2. Samar Mansour
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  3. Nahed D. Mortada
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  4. A. A. El Shamy
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Correspondence to Maha Nasr.

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Nasr, M., Mansour, S., Mortada, N.D. et al. Lipospheres as Carriers for Topical Delivery of Aceclofenac: Preparation, Characterization and In Vivo Evaluation. AAPS PharmSciTech 9, 154–162 (2008). https://doi.org/10.1208/s12249-007-9028-2

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  • DOI: https://doi.org/10.1208/s12249-007-9028-2

Key words

  • aceclofenac
  • animal experiment
  • entrapment
  • formulation
  • lipospheres
  • stability
  • sustained release