Skip to main content
SpringerLink
Log in

NanoCrySP technology for generation of drug nanocrystals: translational aspects and business potential

  • Short Communication
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Drug nanocrystals have rapidly evolved into a mature drug delivery strategy in the last decade, with almost 16 products currently on the market. Several “top-down” technologies are available in the market for generation of nanocrystals. Despite several advantages, very few bottom-up technologies have been explored for commercial purpose. This short communication highlights a novel, bottom-up, spray drying based technology—NanoCrySP—to generate drug nanocrystals. Nanocrystals are generated in the presence of non-polymeric excipients that act as crystallization inducer for the drug. Excipients encourage crystallization of drug by plasticization, primary heterogeneous nucleation, and imparting physical barrier to crystal growth. Nanocrystals have shown significant improvement in dissolution and thereby oral bioavailability. NanoCrySP technology is protected through patents in India, the USA, and the European Union. NanoCrySP can be utilized for (i) pharmaceutical development of new chemical entities, (ii) differentiated products of existing molecules, and (iii) generic drug products. The aggregation of drug nanocrystals generated using NanoCrySP poses significant challenges in the nanocrystal-based product development. Addition of stabilizers either during spray drying or during dissolution has shown beneficial effects.

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

References

  1. Kaushal AM, Gupta P, Bansal AK. Amorphous drug delivery systems: molecular aspects, design and performance. Crit Rev Ther Drug. 2004;21(3):133–93.

    Article  CAS  Google Scholar 

  2. Elder DP, Holm R, de Diego HL. Use of pharmaceutical salts and cocrystals to address the issue of poor solubility. Int J Pharm. 2013;453(1):88–100.

    Article  CAS  PubMed  Google Scholar 

  3. Chaumeil J. Micronization: a method of improving the bioavailability of poorly soluble drugs. Methods Find Exr Clin. 1998;20(3):211–6.

    CAS  Google Scholar 

  4. Jouyban-Gharamaleki A, Valaee L, Barzegar-Jalali M, Clark BJ, Acree Jr WE. Comparison of various cosolvency models for calculating solute solubility in water-cosolvent mixtures. Int J Pharm. 1999;177(1):93–101.

    Article  CAS  PubMed  Google Scholar 

  5. Teja SB, Patil SP, Shete G, Patel S, Bansal AK. Drug-excipient behavior in polymeric amorphous solid dispersions. J Ex Food Chem. 2013;4(3):70–94.

    Google Scholar 

  6. Stella VJ, Rajewski RA. Cyclodextrins: their future in drug formulation and delivery. Pharm Res. 1997;14(5):556–67.

    Article  CAS  PubMed  Google Scholar 

  7. Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12(11):1561–72.

    Article  CAS  PubMed  Google Scholar 

  8. Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanopart Res. 2008;10(5):845–62.

    Article  CAS  Google Scholar 

  9. Che E, Zheng X, Sun C, Chang D, Jiang T, Wang S. Drug nanocrystals: a state of the art formulation strategy for preparing the poorly water-soluble drugs. Asian J Pharm Sci. 2012;7(2):85–95.

    Google Scholar 

  10. de Waard H, Frijlink HW, Hinrichs WL. Bottom-up preparation techniques for nanocrystals of lipophilic drugs. Pharm Res. 2011;28(5):1220–3.

    Article  PubMed  Google Scholar 

  11. Gao L, Liu G, Ma J, Wang X, Zhou L, Li X. Drug nanocrystals: in vivo performances. J Control Release. 2012;160:418–30.

    Article  CAS  PubMed  Google Scholar 

  12. Keck C, Kobierski S, Mauludin R, Müller RH. Second generation of drug nanocrystals for delivery of poorly soluble drugs: smartCrystals technology. Dosis. 2008;24(2):124–8.

    Google Scholar 

  13. Müller RH, Gohla S, Keck CM. State of the art of nanocrystals- special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9.

    Article  PubMed  Google Scholar 

  14. Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1):129–39.

    Article  CAS  PubMed  Google Scholar 

  15. Sinha B, Müller RH, Möschwitzer JP. Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm. 2013;453(1):126–41.

    Article  CAS  PubMed  Google Scholar 

  16. Keck CM, Müller RH. Nanotoxicological classification system (NCS)—a guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur J Pharm Biopharm. 2013;84:445–8.

    Article  CAS  PubMed  Google Scholar 

  17. Hasa D, Perissutti B, Voinovich D, Abrami M, Farra R, Fiorentino S, et al. Drug nanocrystals: theoretical background of solubility increase and dissolution rate enhancement. Chem Biochem Eng Q. 2014;28:247–58.

    Article  CAS  Google Scholar 

  18. Salazar J, Müller RH, Möschwitzer JP. Combinative particle size reduction technologies for the production of drug nanocrystals. J Pharm. 2014;2014:1–14.

    Google Scholar 

  19. Srivalli KM, Mishra B. Drug nanocrystals: four basic prerequisites for formulation development and scale-up. Curr Drug Targets. 2015;16:136–47.

    Article  PubMed  Google Scholar 

  20. Gao Y, Wang J, Wang Y, Yin Q, Glennon B, Zhong J, et al. Crystallization methods for preparation of nanocrystals for drug delivery system. Curr Pharm Des. 2015;21:3131–9.

    Article  CAS  PubMed  Google Scholar 

  21. Xia D, Gan Y, Cui F. Application of precipitation methods for the production of water-insoluble drug nanocrystals: production techniques and stability of nanocrystals. Curr Pharm Des. 2014;20:408–35.

    Article  CAS  PubMed  Google Scholar 

  22. Dan J, Ma Y, Yue P, Xie Y, Zheng Q, Hu P, et al. Microcrystalline cellulose-carboxymethyl cellulose sodium as an effective dispersant for drug nanocrystals: a case study. Carbohydr Polym. 2016;136:499–506.

    Article  CAS  PubMed  Google Scholar 

  23. Fuhrmann K, Gauthier MA, Leroux J-C. Targeting of injectable drug nanocrystals. Mol Pharm. 2014;11:1762–71.

    Article  CAS  PubMed  Google Scholar 

  24. Seybold AR, Li T, Chen Y. Cellular uptake of drug nanocrystals. 2014.

  25. Peltonen L, Strachan C. Understanding critical quality attributes for nanocrystals from preparation to delivery. Molecules. 2015;20:22286–222300.

    Article  CAS  PubMed  Google Scholar 

  26. Lu Y, Chen Y, Gemeinhart RA, Wu W, Li T. Developing nanocrystals for cancer treatment. Nanomedecine. 2015;10:2537–52.

    Article  CAS  Google Scholar 

  27. Junghanns JUAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Bansal AK, Dantuluri AKR, Shete G, Pawar YB. Nanocrystalline solid dispersion compositions and process of preparation thereof. WO 2013132457 A2. Patent Co-operation Treaty Office, Geneva, Switzerland; 2013.

  29. Shete G, Pawar YB, Thanki K, Jain S, Bansal AK. Oral bioavailability and pharmacodynamic activity of hesperetin nanocrystals generated using a novel bottom-up technology. Mol Pharm. 2015;12(4):1158–70.

    Article  CAS  PubMed  Google Scholar 

  30. Shete G, Jain H, Punj D, Prajapat H, Akotiya P, Bansal AK. Stabilizers used in nanocrystal based drug delivery systems. J Ex Food Chem. 2014;5(4):184–209.

    Google Scholar 

  31. Shete G, Modi SR, Bansal AK. Effect of mannitol on nucleation and crystal growth of amorphous flavonoids: implications on the formation of nanocrystalline solid dispersion. J Pharm Sci. 2015;104:3789–97.

    Article  CAS  PubMed  Google Scholar 

  32. Bhatt V, Shete G, Bansal AK. Mechanism of generation of drug nanocrystals in celecoxib: mannitol nanocrystalline solid dispersion. Int J Pharm. 2015;495:132–9.

    Article  CAS  PubMed  Google Scholar 

  33. De Waard H, Hinrichs W, Frijlink H. A novel bottom-up process to produce drug nanocrystals: controlled crystallization during freeze-drying. J Control Release. 2008;128(2):179–83.

    Article  PubMed  Google Scholar 

  34. Jacobs C, Kayser O, Müller R. Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide. Int J Pharm. 2000;196(2):161–4.

    Article  CAS  PubMed  Google Scholar 

  35. Shete G, Khomane KS, Bansal AK. Molecular relaxation behavior and isothermal crystallization above glass transition temperature of amorphous hesperetin. J Pharm Sci. 2014;103:167–78.

    Article  CAS  PubMed  Google Scholar 

  36. Broadhead J, Rouan SKE, Rhodes CT. The spray drying of pharmaceuticals. Drug Dev Ind Pharm. 1992;18(11 & 12):1169–206.

    Article  CAS  Google Scholar 

  37. Kaushal AM, Bansal AK. Thermodynamic behavior of glassy state of structurally related compounds. Eur J Pharm Biopharm. 2008;69(3):1067–76.

    Article  CAS  PubMed  Google Scholar 

  38. Oxtoby DW. Nucleation of first-order phase transitions. Acc Chem Res. 1998;31(2):91–7.

    Article  CAS  Google Scholar 

  39. Yin SX, Franchini M, Chen J, Hsieh A, Jen S, Lee T, et al. Bioavailability enhancement of a COX 2 inhibitor, BMS 347070, from a nanocrystalline dispersion prepared by spray drying. J Pharm Sci. 2005;94(7):1598–607.

    Article  CAS  PubMed  Google Scholar 

  40. Ostwald W. Studien uber die Umwandlung und Bildung fester Korper. Z Phys Chem. 1897;22:289.

    CAS  Google Scholar 

  41. Gao L, Liu G, Ma J, Wang X, Zhou L, Li X, et al. Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs. Pharm Res. 2013;30(2):307–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Ganesh Shete acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India, for providing Senior Research Fellowship.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector-67, Mohali, Punjab, 160 062, India

    Ganesh Shete & Arvind Kumar Bansal

Authors
  1. Ganesh Shete
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arvind Kumar Bansal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arvind Kumar Bansal.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shete, G., Bansal, A.K. NanoCrySP technology for generation of drug nanocrystals: translational aspects and business potential. Drug Deliv. and Transl. Res. 6, 392–398 (2016). https://doi.org/10.1007/s13346-016-0286-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-016-0286-y

Keywords

Search

Navigation