Skip to main content
SpringerLink
Log in

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.

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
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

REFERENCES

  1. Serajuddin ATM. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88(10):1058–66. doi:10.1021/js980403l.

    Article  CAS  PubMed  Google Scholar 

  2. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poorly water soluble drugs. Drug Discov Today. 2007;12(23/24):1068–74. doi:10.1016/j.drudis.2007.09.005.

    Article  CAS  PubMed  Google Scholar 

  3. Bikiaris DN. Solid dispersions, part I: recent evolutions and future opportunities in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs. Expert Opin Drug Deliv. 2011;8(11):1501–19. doi:10.1517/17425247.2011.618181.

    Article  CAS  PubMed  Google Scholar 

  4. Craig DQM. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002;231:131–44. doi:10.1016/S0378-5173(01)00891-2.

    Article  CAS  PubMed  Google Scholar 

  5. Barzegar-Jalali M, Valizadeh H, Shadbad MS, Adibkia K, Mohammadi G, Farahani A, et al. Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide). Powder Technol. 2010;197:150–8. doi:10.1016/j.powtec.2009.09.008.

    Article  CAS  Google Scholar 

  6. Colombo I, Grassi G, Grass M. Drug mechanochemical activation. J Pharm Sci. 2009;98(11):3961–86. doi:10.1002/jps.21733.

    Article  CAS  PubMed  Google Scholar 

  7. Dushkin AV. Mechanochemical synthesis of organic compounds and rapidly-soluble materials. High-energy ball milling: mechanochemical processing of nanopowders. Cambridge, UK: Woodhead Publishing Limited; 2010. p. 224–47.

    Google Scholar 

  8. Corti G, Capasso G, Maestrelli F, Cirri M, Mura P. Physical–chemical characterization of binary systems of metformin hydrochloride with triacetyl-β-cyclodextrin. J Pharm Biomed Anal. 2007;45:480–6. doi:10.1016/j.jpba.2007.07.018.

    Article  CAS  PubMed  Google Scholar 

  9. Tran PHL, Tran HTT, Lee BJ. Modulation of microenvironmental pH and crystallinity of ionizable telmisartan using alkalizers in solid dispersions for controlled release. J Control Release. 2008;129:59–65. doi:10.1016/j.jconrel.2008.04.001.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang Y, Zhi Z, Jiang T, Zhang J, Wang Z, Wang S. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010;145:257–63. doi:10.1016/j.jconrel.2010.04.029.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang Y, Jiang T, Zhang Q, Wang S. Inclusion of telmisartan in mesocellular foam nanoparticles: drug loading and release property. Eur J Pharm Biopharm. 2010;76:17–23. doi:10.1016/j.ejpb.2010.05.010.

    Article  CAS  PubMed  Google Scholar 

  12. Koilkonda P, Lekkala AR, Mala C, Golla K, Ganji SR, Konda RB. Amorphous telmisartan. US Patent 2006/0111417 A1.

  13. Ravi Kumar MNV, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ. Chitosan chemistry and pharmaceutical perspectives. Chem Rev. 2004;104:6017–84. doi:10.1021/cr030441b.

    Article  Google Scholar 

  14. Mura P, Zerrouk N, Mennini N, Maestrelli F, Chemtob C. Development and characterization of naproxen–chitosan solid systems with improved drug dissolution properties. Eur J Pharm Sci. 2003;19:67–75. doi:10.1016/S0928-0987(03)00068-X.

    Article  CAS  PubMed  Google Scholar 

  15. Kumar SGV, Mishra DN. Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan. Chem Pharm Bull. 2006;54(8):1102–6. doi:10.1248/cpb.54.1102.

    Article  Google Scholar 

  16. Portero A, Remuñán-López C, Vila-Jato JL. Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm. 1998;175:75–84. doi:10.1016/S0378-5173(98)00245-2.

    Article  CAS  Google Scholar 

  17. Sawayanagi Y, Nambu N, Nagai T. Dissolution properties and bioavailability of phenytoin from ground mixtures with chitin or chitosan. Chem Pharm Bull. 1983;31:2062–8. doi:10.1248/cpb.31.2064.

    Google Scholar 

  18. Sheng Y, Zheng F, Zhong F. The effect of chitosan on dissolution properties of griseofulvin. J China Pharm Univ. 1993;24(6):376–9.

    CAS  Google Scholar 

  19. Maestrelli F, Cirri M, Mennini N, Zerrouk N, Mura P. Improvement of oxaprozin solubility and permeability by the combined use of cyclodextrin, chitosan, and bile components. Eur J Pharm Biopharm. 2011;78:385–93. doi:10.1016/j.ejpb.2011.03.012.

    Article  CAS  PubMed  Google Scholar 

  20. Corti G, Maestrelli F, Cirri M, Mura P, Zerrouk N. Dissolution and permeation properties of naproxen from solid-state systems with chitosan. Drug Deliv. 2008;15:303–12. doi:10.1080/10717540802006955.

    Article  CAS  PubMed  Google Scholar 

  21. Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59:645–66. doi:10.1016/j.addr.2007.05.012.

    Article  CAS  PubMed  Google Scholar 

  22. Lina S, Hsua C, Sheub M. Curve-fitting FTIR studies of loratadine/hydroxypropyl-β-cyclodextrin inclusion complex induced by co-grinding process. J Pharm Biomed Anal. 2010;53:799–803. doi:10.1016/j.jpba.2010.06.010.

    Article  Google Scholar 

Download references

ACKNOWLEDGMENTS

We are grateful to the Natural Science Foundation of China (No. 21006097, 21076191, and 21176222), the Science and Technology Program of Zhejiang Province (No. 2009C14001), and the Program of International S&T Cooperation (No. 2008DFR40280) for financial support.

Author information

Authors and Affiliations

  1. Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Lin Zhong, Xingyi Zhu, Xiaofang Luo & Weike Su

Authors
  1. Lin Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xingyi Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaofang Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weike Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weike Su.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhong, L., Zhu, X., Luo, X. et al. Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation. AAPS PharmSciTech 14, 541–550 (2013). https://doi.org/10.1208/s12249-013-9937-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-013-9937-1

KEY WORDS

Search

Navigation