AAPS PharmSciTech

, Volume 13, Issue 4, pp 1331–1340 | Cite as

Nanocrystallization by Evaporative Antisolvent Technique for Solubility and Bioavailability Enhancement of Telmisartan

  • Amrita Bajaj
  • Monica R. P. Rao
  • Amol Pardeshi
  • Dhanesh Sali
Research Article


Telmisartan is an orally active nonpeptide angiotensin II receptor antagonist used in the management of hypertension. It is a Biopharmaceutics Classification System class II drug having aqueous solubility of 9.9 μg/ml. Telmisartan (TEL) nanocrystals were prepared by evaporative antisolvent precipitation technique using different stabilizers as PVPK30, TPGS, Poloxamer 188, and PEG 6000 in combination or singly. The nanosuspensions were characterized in terms of particle size distribution, zeta potential, and polydispersity index. The suspension containing PVPK30 and TPGS (1:1) showed least average particle size of 82.63 nm and polydispersity index of 0.472. The zeta potential of nanosuspensions ranged between 6.54 and 10.8 mV. An increase of 116.45% was evident in the specific surface area of the freeze-dried product. Contact angle of nanoparticles was also lowered to 27° as compared to 50.8° for TEL. Saturation solubility studies in various media revealed a significant increase in comparison to plain drug. An increase of 3.74× in saturation solubility in FaSSIF and 5.02× in FeSSIF was seen. In vitro dissolution profile of nanosuspension coated on pellets revealed release of 85% in water, 95% in 0.1 N HCl, and 75% in phosphate buffer in 30 min. Nanosuspensions were found to be stable in the presence of univalent and bivalent electrolytes. A tenfold increase in bioavailability was evident. Nanoparticles of telmisartan prepared by bottom-up technique proved to be effective in improving the oral bioavailability as a result of enhanced solubility and dissolution rate.

Key words

biorelevant media contact angle specific surface area telmisartan TPGS 



The authors would like to acknowledge Dr. Jay Kannan (IISER, Pune), Mr. Tamhane (SP Consultants, Mumbai), Dr. RA Joshi (NCL, Pune) and Dr. Shouche (NCCS, Pune) for their help in the study.


  1. 1.
    Vandecruys R, Peeters J, Verreck G, Brewster M. Use of screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design. Int J Pharm. 2007;342:168–75.PubMedCrossRefGoogle Scholar
  2. 2.
    Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Del Rev. 2007;59:617–30.CrossRefGoogle Scholar
  3. 3.
    Kim C, Park J. Solubility enhancement for oral delivery: can chemical structure modification be avoided? Am J Drug Deliv. 2004;2:113–30.CrossRefGoogle Scholar
  4. 4.
    Merisko-Liversidge E, Liversidge G, Cooper E. Nanosizing: a formulation approach for poorly water soluble compounds. Eur J Pharm Sci. 2003;18:113–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Humberstone A, Charman W. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Del Rev. 1997;25:103–28.CrossRefGoogle Scholar
  6. 6.
    Forster A, Rades T, Hempenstall J. Selection of suitable drug and excipient candidates to prepare glass solutions by melt extrusion for immediate release oral formulations. Pharm Tech Eur. 2002;14:27–37.Google Scholar
  7. 7.
    Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present, future. Rev Drug Discov. 2004;3:1023–35.CrossRefGoogle Scholar
  8. 8.
    Keck C, Muller R. Drug nanoparticles of poorly soluble drugs produced by high pressure homogenization. Eur J Pharm Biopharm. 2006;62:3–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Timpe C. Oral drug solubilization strategies: applying nanoparticulate formulation and solid dispersion approaches in drug development. Featured Article in APV Drug Delivery Focus Group Newsletter. 2010:1.Google Scholar
  10. 10.
    Huang P, Wang X, Chen Z. Micronization of gemfibrozil by reactive precipitation process. Int J Pharm. 2008;360:58–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Kocbeck P, Baumgartner S, Kristl J. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int J Pharm. 2006;312:179–86.CrossRefGoogle Scholar
  12. 12.
    Dressman J, Amidon GL, Reppas C, Shah V. Dissolution testing as a prognostic tool for oral drug. Absorption: immediate release dosage forms. Pharm Res. 1988;15:11–22.CrossRefGoogle Scholar
  13. 13.
  14. 14.
    Matteucci M, Hotze M, Johnston K, Williams R. Drug nanoparticles by antisolvent precipitation:mixing energy vs surfactant stabilization. Langmuir. 2006;22:8951–9.PubMedCrossRefGoogle Scholar
  15. 15.
    van Eerdenbrugh B, Froyen L, van Humbeeck J, Martens J, Augustijns P, van den Mooter G. Top-down production of drug nanoparticles: nanosuspension stabilization, miniaturization and transformation into solid products. Int J Pharm. 2008;364:64–75.PubMedCrossRefGoogle Scholar
  16. 16.
  17. 17.
    Born P, Klaessig FC, Landry TD, Moudgil M, Pauluhn J, Thomas K, Trottier R, Wood S. Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles. Toxicol Sci. 2006;90(1):23–32.CrossRefGoogle Scholar
  18. 18.
    Bisrat M, Anderberg EK, Barnett MI, Nyström C. Physicochemical aspects of drug release XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs. Int J Pharm. 1992;80:191–201.CrossRefGoogle Scholar
  19. 19.
    Weinen W, Entzeroth M, Jacobus C. A review on Telmisartan: a novel, long-acting angiotensin II-receptor antagonist. Cardiovascular Drug Reviews. 2000;18(2):127–54.CrossRefGoogle Scholar
  20. 20.
    Sinko Patrick J. Martin’s physical pharmacy and pharmaceutical sciences. 5th ed. Philadelphia: Lippincott Williams & Williams; 2006. p. 486.Google Scholar
  21. 21.
    Panchagnula R, Dhanikula A, Singh R. In vivo pharmacokinetic and tissue distribution studies in mice of alternative formulations for local and systemic delivery of paclitaxel: gel, film, prodrug, liposomes and micelles. Curr Drug Del. 2005;2:35–44.CrossRefGoogle Scholar
  22. 22.
    Liversidge GG, Conzentino P. Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats. Int J Pharm. 1995;125:309–13.CrossRefGoogle Scholar
  23. 23.
    Higuchi W, Swarbick J, Ho N, Simonelli AP, Martin A. In: Gennaro AR, editor. Remington’s pharmaceutical sciences. Easton: Mack; 1985. p. 301–29.Google Scholar
  24. 24.
    Wei L, Yonggang Y, Yongshou T. Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride. Int J Pharm. 2011;408:157–62.CrossRefGoogle Scholar
  25. 25.
    Jani P, Halbert G, Langridge J, Florence AT. Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency. J Pharm Pharmacol. 1990;42:821–6.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Amrita Bajaj
    • 1
  • Monica R. P. Rao
    • 2
  • Amol Pardeshi
    • 2
  • Dhanesh Sali
    • 2
  1. 1.Department of PharmaceuticsSVKM’S B.N. College of PharmacyMumbaiIndia
  2. 2.Department of PharmaceuticsAISSMS College of PharmacyPuneIndia

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