Skip to main content
SpringerLink
Log in

Solubility of Drugs in Aqueous Polymeric Solution: Effect of Ovalbumin on Microencapsulation Process

  • Research Article
  • Theme: Advanced Technologies for Oral Controlled Release
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Benoit JP, Marchais H, Rolland H, Velde VV. Biodegradable microspheres: advances in production technology. In: Benita S, editor. Microencapsulation methods and industrial applications. New York: Marcel Dekker; 1996. p. 36–62.

    Google Scholar 

  2. Cruaud O, Benita S, Benoit JP. The characterization and release kinetics evaluation of baclofen microspheres designed for intrathecal injection. Int J Pharm. 1999;177(2):247–57.

    Article  PubMed  CAS  Google Scholar 

  3. Freytag T, Dashevsky A, Tillman L, Hardee GE, Bodmeier R. Improvement of the encapsulation efficiency of oligonucleotide-containing biodegradable microspheres. J Control Release. 2000;69(1):197–207.

    Article  PubMed  CAS  Google Scholar 

  4. Hombreiro Pérez M, Zinutti C, Lamprecht A, Ubrich N, Astier A, Hoffman M, et al. The preparation and evaluation of poly([epsilon]-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug. J Control Release. 2000;65(3):429–38.

    Article  PubMed  Google Scholar 

  5. Passerini N, Perissutti B, Albertini B, Voinovich D, Moneghini M, Rodriguez L. Controlled release of verapamil hydrochloride from waxy microparticles prepared by spray congealing. J Control Release. 2003;88(2):263–75.

    Article  PubMed  CAS  Google Scholar 

  6. Ubrich N, Bouillot P, Pellerin C, Hoffman M, Maincent P. Preparation and characterization of propranolol hydrochloride nanoparticles: a comparative study. J Control Release. 2004;97(2):291–300.

    Article  PubMed  CAS  Google Scholar 

  7. Meng FT, Ma GH, Qiu W, Su ZG. W/O/W double emulsion technique using ethyl acetate as organic solvent: effects of its diffusion rate on the characteristics of microparticles. J Control Release. 2003;91(3):407–16.

    Article  PubMed  CAS  Google Scholar 

  8. Hasan AS, Socha M, Lamprecht A, Ghazouani FE, Sapin A, Hoffman M, et al. Effect of the microencapsulation of nanoparticles on the reduction of burst release. Int J Pharm. 2007;344(1–2):53–61.

    Article  PubMed  CAS  Google Scholar 

  9. Cohen-Sela E, Chorny M, Koroukhov N, Danenberg HD, Golomb G. A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. J Control Release. 2009;133(2):90–5.

    Article  PubMed  CAS  Google Scholar 

  10. Puri S, Kallinteri P, Higgins S, Hutcheon GA, Garnett MC. Drug incorporation and release of water soluble drugs from novel functionalised poly(glycerol adipate) nanoparticles. J Control Release. 2008;125(1):59–67.

    Article  PubMed  CAS  Google Scholar 

  11. Yeo Y, Basaran OA, Park K. A new process for making reservoir-type microcapsules using ink-jet technology and interfacial phase separation. J Control Release. 2003;93(2):161–73.

    Article  PubMed  CAS  Google Scholar 

  12. Lecomte F, Siepmann J, Walther M, MacRae RJ, Bodmeier R. Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer. J Control Release. 2004;99(1):1–13.

    Article  PubMed  CAS  Google Scholar 

  13. Nii T, Ishii F. Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int J Pharm. 2005;298(1):198–205.

    Article  PubMed  CAS  Google Scholar 

  14. Lee S, Kim MS, Kim JS, Park HJ, Woo JS, Lee BC, et al. Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique. J Microencapsul. 2006;23:741–9.

    Article  PubMed  CAS  Google Scholar 

  15. Qi M, Li X, Yang Y, Zhou S. Electrospun fibers of acid-labile biodegradable polymers containing ortho ester groups for controlled release of paracetamol. Eur J Pharm Biopharm. 2008;70(2):445–52.

    Article  PubMed  CAS  Google Scholar 

  16. Shi G, Rao L, Yu H, Xiang H, Pen G, Long S, et al. Yeast-cell-based microencapsulation of chlorogenic acid as a water-soluble antioxidant. J Food Eng. 2007;80(4):1060–7.

    Article  CAS  Google Scholar 

  17. Jin K-M, Kim Y-H. Injectable, thermo-reversible and complex coacervate combination gels for protein drug delivery. J Control Release. 2008;127(3):249–56.

    Article  PubMed  CAS  Google Scholar 

  18. Bae SE, Son JS, Park K, Han DK. Fabrication of covered porous PLGA microspheres using hydrogen peroxide for controlled drug delivery and regenerative medicine. J Control Release. 2009;133(1):37–43.

    Article  PubMed  CAS  Google Scholar 

  19. Aziz HA, Peh KK, Tan YTF. Solubility of core materials in aqueous polymeric solution effect on microencapsulation of curcumin. Drug Dev Ind Pharm. 2007;33(11):1263–72.

    Article  PubMed  CAS  Google Scholar 

  20. Aziz HHHA. Microencapsulation of curcumin and turmeric oil extracted from turmeric rhizome and application in cream preparation. Pulau Pinang: Universiti Sains Malaysia; 2006.

    Google Scholar 

  21. Chang R-K, Robinson JR. Sustained drug release from tablets and particles throuph coating. In: Lieberman HA, Lachman L, Schwartz JB, editors. Pharmaceutical dosage forms-tablets. 2nd ed. Iowa: Informa Health Care; 1990. p. 199–287.

    Google Scholar 

  22. Deasy PB. Coacervation-phase separation procedures using aqueous vehicles. In: Swarbrick J, editor. Drugs and pharmaceutical sciences: microencapsulation and related drug processes. New York: Marcel Dekker; 1984. p. 61–95.

    Google Scholar 

  23. Awadé AC, Efstathiou T. Comparison of three liquid chromatographic methods for egg-white protein analysis. J Chromatogr B: Biomed Sci Appl. 1999;723(1–2):69–74.

    Article  Google Scholar 

  24. Chang Y-K, Chang I-P. Method development for direct recovery of lysozyme from highly crude chicken egg white by stirred fluidized bed technique. Biochem Eng J. 2006;30(1):63–75.

    Article  CAS  Google Scholar 

  25. Datta D, Bhattacharjee S, Nath A, Das R, Bhattacharjee C, Datta S. Separation of ovalbumin from chicken egg white using two-stage ultrafiltration technique. Sep Purif Technol. 2009;66(2):353–61.

    Article  CAS  Google Scholar 

  26. Jerez A, Partal P, Martínez I, Gallegos C, Guerrero A. Egg white-based bioplastics developed by thermomechanical processing. J Food Eng. 2007;82(4):608–17.

    Article  CAS  Google Scholar 

  27. Van der Plancken I, Van Loey A, Hendrickx ME. Combined effect of high pressure and temperature on selected properties of egg white proteins. Innovat Food Sci Emerg Tech. 2005;6(1):11–20.

    Article  Google Scholar 

  28. Brophy MR, Deasy PB. Egg albumin microspheres containing sulphamethizole. J Microencapsul. 1984;1(2):157–68.

    Article  PubMed  CAS  Google Scholar 

  29. Ishizaka T, Endo K, Koishi M. Preparation of egg albumin microcapsules and microspheres. J Pharm Sci. 1981;70(4):358–63.

    Article  PubMed  CAS  Google Scholar 

  30. Ishizaka T, Koishi M. In vitro drug release from egg albumin microcapsules. J Pharm Sci. 1983;72(9):1057–61.

    Article  PubMed  CAS  Google Scholar 

  31. Jun HW, Lai JW. Preparation and in vitro dissolution tests of egg albumin microcapsules of nitrofurantoin. Int J Pharm. 1983;16(1):65–77.

    Article  CAS  Google Scholar 

  32. Torrado JJ, Illum L, Cadorniga R, Davis SS. Egg albumin microspheres containing paracetamol for oral administration. I. In vitro characterization. J Microencapsul. 1990;7(4):463–70.

    Article  PubMed  CAS  Google Scholar 

  33. Blanco-Príeto MJ, Fattal E, Gulik A, Dedieu JC, Roques BP, Couvreur P. Characterization and morphological analysis of a cholecystokinin derivative peptide-loaded poly(lactide-co-glycolide) microspheres prepared by a water-in-oil-in-water emulsion solvent evaporation method. J Control Release. 1997;43(1):81–7.

    Article  Google Scholar 

  34. Hu Y, Jiang X, Ding Y, Zhang L, Yang C, Zhang J, et al. Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)-poly(ethylene oxide)-polylactide amphiphilic copolymer nanoparticles. Biomaterials. 2003;24(13):2395–404.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Fellowship from Institute of Postgraduate Studies (IPS) and funding RU-grant (1001/815001) from Universiti Sains Malaysia (USM) are gratefully acknowledged.

Author information

Authors and Affiliations

  1. Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Hesham Abdul Aziz, Yvonne Tze Fung Tan & Kok Khiang Peh

  2. College of Pharmacy, Qassim University, P.O. Box 6800, Buraidah, 51452, Qassim, Saudi Arabia

    Hesham Abdul Aziz

Authors
  1. Hesham Abdul Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvonne Tze Fung Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kok Khiang Peh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kok Khiang Peh.

Additional information

Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aziz, H.A., Tan, Y.T.F. & Peh, K.K. Solubility of Drugs in Aqueous Polymeric Solution: Effect of Ovalbumin on Microencapsulation Process. AAPS PharmSciTech 13, 35–45 (2012). https://doi.org/10.1208/s12249-011-9707-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-011-9707-x

Key words

Search

Navigation