AAPS PharmSciTech

, Volume 13, Issue 4, pp 1416–1427 | Cite as

Development, Optimization, and Characterization of Solid Self-Nanoemulsifying Drug Delivery Systems of Valsartan Using Porous Carriers

  • Sarwar Beg
  • Suryakanta Swain
  • Harendra Pratap Singh
  • Ch Niranjan Patra
  • ME Bhanoji Rao
Research Article


The present studies entail formulation development of novel solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of valsartan with improved oral bioavailability, and evaluation of their in vitro and in vivo performance. Preliminary solubility studies were carried out and pseudoternary phase diagrams were constructed using blends of oil (Capmul MCM), surfactant (Labrasol), and cosurfactant (Tween 20). The SNEDDS were systematically optimized by response surface methodology employing 33-Box–Behnken design. The prepared SNEDDS were characterized for viscocity, refractive index, globule size, zeta potential, and TEM. Optimized liquid SNEDDS were formulated into free flowing granules by adsorption on the porous carriers like Aerosil 200, Sylysia (350, 550, and 730) and Neusilin US2, and compressed into tablets. In vitro dissolution studies of S-SNEDDS revealed 3–3.5-fold increased in dissolution rate of the drug due to enhanced solubility. In vivo pharmacodynamic studies in Wistar rats showed significant reduction in mean systolic BP by S-SNEDDS vis-à-vis oral suspension (p < 0.05) owing to the drug absorption through lymphatic pathways. Solid-state characterization of S-SNEDDS using FT-IR and powder XRD studies confirmed lack of any significant interaction of drug with lipidic excipients and porous carriers. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS are found to be stable without any change in physiochemical properties. Thus, the present studies demonstrated the bioavailability enhancement potential of porous carriers based S-SNEDDS for a BCS class II drug, valsartan.


BCS bioavailability in vitro dissolution porous carriers XRD 



The authors are highly thankful to SAIF Panjab University, Chandigarh for carrying out the powder X-ray diffraction study and also thankful to Institute of Life Sciences, Bhubaneswar for providing the facility to determine the globule size and AIIMS, New Delhi for TEM study.

Conflict of Interest

Authors declare no conflict(s) of interest.


  1. 1.
    Chioléro A, Burnier M. Pharmacology of valsartan, an angiotensin II receptor antagonist. Expert Opin Investig Drugs. 1998;7:1915–25.CrossRefPubMedGoogle Scholar
  2. 2.
    Valsartan. Drug bank. Accessed on 12 August 2011.
  3. 3.
    Park YJ, Lee HK, Im YB, Lee W, Han HK. Improved pH-independent dissolution and oral absorption of valsartan via the preparation of solid dispersion. Arch Pharm Res. 2010;33:1235–40.CrossRefPubMedGoogle Scholar
  4. 4.
    Dixit AR, Rajput SJ, Patel SG. Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS Pharm Sci Tech. 2010;11:314–21.CrossRefGoogle Scholar
  5. 5.
    Yana YD, Sunga JH, Kima KK, Kimb DW, Kima JO, Leec BJ, Yonga CS, Cho HG. Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes. Int J Pharm. 2012;422:202–10.CrossRefGoogle Scholar
  6. 6.
    Shrivastava AR, Kapadia UB. Design, optimization, preparation and evaluation of dispersion granules of valsartan and formulation into tablets. Curr Drug Deliv. 2009;6:28–37.CrossRefPubMedGoogle Scholar
  7. 7.
    Liyan W. Valsartan liposome, preparation method thereof and medicinal composition containing same, CN 101819580 (2010)Google Scholar
  8. 8.
    Singh B, Khurana L, Bandyopadhyay S, Kapil R, Katare OP. Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential. Drug Deliv. 2011;18:599–612.PubMedGoogle Scholar
  9. 9.
    Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12:1561–72.CrossRefPubMedGoogle Scholar
  10. 10.
    Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58:173–82.CrossRefPubMedGoogle Scholar
  11. 11.
    Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev. 1997;25:47–58.CrossRefGoogle Scholar
  12. 12.
    Mou D, Chen H, Du D, Mao C, Wan J, Xu H, Yang X. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm. 2008;353:270–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Porter CJH, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev. 2008;60:673–91.CrossRefPubMedGoogle Scholar
  14. 14.
    Cole ET, Cadé D, Benameur H. Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration. Adv Drug Deliv Rev. 2008;60:747–56.CrossRefPubMedGoogle Scholar
  15. 15.
    Kohli K, Chopra S, Dhar D, Arora S, Khar RK. Self-emulsifying drug delivery systems: an approach to enhance oral bioavailability. Drug Discov Today. 2010;15:958–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today. 2008;13:606–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Singh A, Worku ZA, vanden Mooter G. Oral formulation strategies to improve solubility of poorly water-soluble drugs. Expert Opin Drug Deliv. 2011;8:1361–78.CrossRefPubMedGoogle Scholar
  18. 18.
    Hwang RC and Kowalski DL. Design of experiments for formulation development. Pharm Tech. 2005,1–5.Google Scholar
  19. 19.
    Singh B, Kumar R, Ahuja N. Optimizing drug delivery systems using systematic “design of experiments.” Part I: fundamental aspects. Crit Rev Ther Drug Carrier Syst. 2005;22(1):27–105.CrossRefPubMedGoogle Scholar
  20. 20.
    Nazzal S, Khan MA. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS Pharm Sci Tech. 2002;3:23–31.CrossRefGoogle Scholar
  21. 21.
    Shaji J, Lodha S. Response surface methodology for the optimization of celecoxib self-microemulsifying drug delivery system. Ind J Pharm Sci. 2008;70:585–90.CrossRefGoogle Scholar
  22. 22.
    Dixit RP, Nagarsenker MS. Self-nanoemulsifying granules of ezetimibe: design, optimization and evaluation. Eur J Pharm Sci. 2008;35:183–92.CrossRefPubMedGoogle Scholar
  23. 23.
    Nazzal S, Nutan M, Palamakula A, Shah R, Zaghloul AA, Khan MA. Optimization of a self-nanoemulsified tablet dosage form of ubiquinone using response surface methodology: effect of formulation ingredients. Int J Pharm. 2002;240:103–14.CrossRefPubMedGoogle Scholar
  24. 24.
    Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001;212:233–46.CrossRefPubMedGoogle Scholar
  25. 25.
    Ahuja G, Pathak K. Porous carriers for controlled/modulated drug delivery. Indian J Pharm Sci. 2009;71:599–607.CrossRefPubMedGoogle Scholar
  26. 26.
    Dissolution methods database. [Online] Available at: Accessed 7 July 2011.
  27. 27.
    Aqil M, Sultana Y, Ali A, Dubey K, Najmi AK, Pillai KK. Transdermal drug delivery systems of a beta blocker: design, in vitro, and in vivo characterization. Drug Deliv. 2004;11:27–31.CrossRefPubMedGoogle Scholar
  28. 28.
    Rizwan M, Aqil M, Azeem A, Talegaonkar S, Sultana Y, Ali A. Enhanced transdermal delivery of carvedilol using nanoemulsion as a vehicle. J Exp Nanosci. 2010;5:390–411.CrossRefGoogle Scholar
  29. 29.
    Beg S, Jena SS, Patra CN, Rizwan M, Swain S, Sruti J, Rao MEB, Singh B. Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloids and Surfaces B: Biointerfaces. 2013;101:414–23.CrossRefGoogle Scholar
  30. 30.
    Wang L, Cui FD, Sunada H. Preparation and evaluation of solid dispersions of nitrendipine prepared with fine silica particles using the melt-mixing method. Chem Pharm Bull. 2006;54:37–43.CrossRefPubMedGoogle Scholar
  31. 31.
    Lee BJ, On DH, Kim JO, Hong MJ, Jee JP, Kim JA, You BK, Wo JS, Yong CS, Choi HG. Enhanced oral bioavailability of dexibuprofen by novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm. 2009;72:539–45.CrossRefPubMedGoogle Scholar
  32. 32.
    Planisek O, Kovacic B, Vrecer F. Carvedilol dissolution improvement by preparation of solid dispersions with porous silica. Int J Pharm. 2011;406:41–8.CrossRefGoogle Scholar
  33. 33.
    Sharma S, Sher P, Bardve S, Atmaram PP. Adsorption of meloxicam on porous calcium silicate: characterization and tablet formulation. AAPS Pharm Sci Tech. 2005;6:E618–25.CrossRefGoogle Scholar
  34. 34.
    Pouton CW. Effects of inclusion of a model drug on the performance of self-emulsifying formulations. J Pharm Pharmacol. 1985;37:1–11.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Sarwar Beg
    • 1
  • Suryakanta Swain
    • 1
  • Harendra Pratap Singh
    • 1
  • Ch Niranjan Patra
    • 1
  • ME Bhanoji Rao
    • 1
  1. 1.Department of PharmaceuticsRoland Institute of Pharmaceutical SciencesBerhampurIndia

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