Skip to main content
SpringerLink
Log in

Improved delivery of poorly soluble compounds using nanoparticle technology: a review

  • Review Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Although a large number of new drug molecules with varied therapeutic potentials have been discovered in the recent decade, yet most of them are still in developmental process. This can be attributed to the limited aqueous solubility which governs the bioavailability of such drug molecules. Hence, there is a requisite for a technology-based product (formulation) in order to overcome such issues without compromising on the therapeutic response. The purpose of this review is to provide an insight to the formulation of drug nanoparticles for enhancing solubility and dissolution velocity with concomitant enhancement in bioavailability. In the recent decade, nanonization has evolved from a concept to reality owing to its versatile applications, especially in the development of drugs having poor solubility. In this review, a relatively simple and scalable approach for the manufacture of drug nanoparticles and latest characterization techniques utilized to evaluate the drug nanoparticles are discussed. The drug nanoparticulate approach described herein provides a general applicability of the platform technology in designing a formulation for drugs associated with poor aqueous solubility.

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

Similar content being viewed by others

References

  1. Lipinski C. Avoiding investment in doomed drugs, is poor solubility an industry wide problem. Curr Drug Dis. 2001;4:17–9.

    Google Scholar 

  2. Lipinski CA. Poor aqueous solubility—an industry wide problem in ADME screening. Am Pharm Rev. 2002;5:82–5.

    Google Scholar 

  3. Müller RH, Peters K. Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. Int J Pharm. 1998;160(2):229–37.

    Article  Google Scholar 

  4. Merisko-Liversidge EM, Liversidge GG. Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol Pathol. 2008;36(1):43–8.

    Article  CAS  PubMed  Google Scholar 

  5. 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 Nanoparticle Res. 2008;10(5):845–62.

    Article  CAS  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Merisko-Liversidge E, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18(2):113–20.

    Article  CAS  PubMed  Google Scholar 

  8. Mohammed A, Weston N, Coombes A, Fitzgerald M, Perrie Y. Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability. Int J Pharm. 2004;285(1):23–34.

    Article  CAS  PubMed  Google Scholar 

  9. Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm. 1995;125(1):91–7.

    Article  CAS  Google Scholar 

  10. Yadollahi R, Vasilev K, Simovic S. Nanosuspension technologies for delivery of poorly soluble drugs. J Nanomater. 2014.

  11. Rogers T, Johnston K, Williams III R. A comprehensive review: solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies. Drug Dev Ind Pharm. 2001;27(10):1003–16.

    Article  CAS  PubMed  Google Scholar 

  12. 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 

  13. Robertson A. The development of ideas on heterogeneous catalysis. Platinum Metals Rev. 1983;27:31–9.

    CAS  Google Scholar 

  14. Dubey R. Impact of nanosuspension technology on drug discovery and development. Drug Deliv Technol. 2006;6(5):67–71.

    Google Scholar 

  15. Saffie-Siebert R, Ogden J, Parry-Billings M. Nanotechnology approaches to solving the problems of poorly water-soluble drugs. Drug Discov World. 2005;6(3):71.

    Google Scholar 

  16. Müller R, Dingler A, Schneppe T, Gohla S. Large scale production of solid lipid nanoparticles (SLN™) and nanosuspensions (DissoCubes™). Handbook of Pharmaceutical Controlled Release Technology. New York: Marcel Dekker; 2000. p. 359–76.

    Google Scholar 

  17. Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2006;62(1):3–16.

    Article  CAS  PubMed  Google Scholar 

  18. Otsuka M, Kaneniwa N. Effect of seed crystals on solid‐state transformation of polymorphs of chloramphenicol palmitate during grinding1. J Pharm Sci. 1986;75(5):506–11.

    Article  CAS  PubMed  Google Scholar 

  19. Illingsworth BD. Preparation of silver halide grains. Google Patents; 1972.

  20. Keritsis GD. Precipitation of metal salts. Google Patents; 1985.

  21. Sjöström B, Bergenståhl B, Kronberg B. A method for the preparation of submicron particles of sparingly water‐soluble drugs by precipitation in oil‐in‐water emulsions. II: influence of the emulsifier, the solvent, and the drug substance. J Pharm Sci. 1993;82(6):584–9.

    Article  PubMed  Google Scholar 

  22. Gassmann P, List M, Schweitzer A, Sucker H. Hydrosols: alternatives for the parenteral application of poorly water soluble drugs. Eur J Pharm Biopharm. 1994;40(2):64–72.

    CAS  Google Scholar 

  23. Sucker H, Gassmann P. Improvements in pharmaceutical compositions. GB Patent A. 1994;2269536:1994.

    Google Scholar 

  24. Kipp JE, Wong JCT, Doty MJ, Rebbeck CL. Microprecipitation method for preparing submicron suspensions. Google Patents; 2003.

  25. Mahajan AJ, Kirwan D. Rapid precipitation of biochemicals. J Phys D Appl Phys. 1993;26(8B):B176.

    Article  CAS  Google Scholar 

  26. Müller RH, Böhm BH. Dispersion techniques for laboratory and industrial scale processing: Wissenschaftliche Verlagsgesellschaft; 2001.

  27. Lonare AA, Patel SR. Antisolvent crystallization of poorly water soluble drugs. Int J Chem Eng Appl. 2013;4:337–41.

    CAS  Google Scholar 

  28. Thorat AA, Dalvi SV. Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: recent developments and future perspective. Chem Eng J. 2012;181:1–34.

    Article  Google Scholar 

  29. Matteucci ME, Hotze MA, Johnston KP, Williams RO. Drug nanoparticles by antisolvent precipitation: mixing energy versus surfactant stabilization. Langmuir. 2006;22(21):8951–9.

    Article  CAS  PubMed  Google Scholar 

  30. Shackleford DM, Faassen WF, Houwing N, Lass H, Edwards GA, Porter CJ, et al. Contribution of lymphatically transported testosterone undecanoate to the systemic exposure of testosterone after oral administration of two andriol formulations in conscious lymph duct-cannulated dogs. J Pharmacol Exp Ther. 2003;306(3):925–33.

    Article  CAS  PubMed  Google Scholar 

  31. Violanto MR. Method for making uniformly sized particles from water-insoluble organic compounds. Google Patents; 1989.

  32. Bruno JA, Doty BD, Gustow E, Illig KJ, Rajagopalan N, Sarpotdar P. Method of grinding pharmaceutical substances. Google Patents; 1996.

  33. Nekkanti V, Venkateswarlu V, Akhter Ansari K, Pillai R. Development and pharmacological evaluation of a PEG based nanoparticulate camptothecin analog for oral administration. Curr Drug Deliv. 2011;8(6):661–6.

    Article  CAS  PubMed  Google Scholar 

  34. Liversidge GG, Cundy KC, Bishop JF, Czekai DA. Dispersion, bioavailability. Google Patents; 1992.

  35. Nekkanti V, Marwah A, Pillai R. Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE). Drug Devel Ind Pharm. 2013;41(1):124–30.

    Article  Google Scholar 

  36. Chu B, Liu T. Characterization of nanoparticles by scattering techniques. J Nanoparticle Res. 2000;2(1):29–41.

    Article  CAS  Google Scholar 

  37. Jain RA, Ruddy SB, Cumming KI, Clancy MJA, Codd JE. Rapidly disintegrating solid oral dosage form. Google Patents; 2001.

  38. Nekkanti V, Pillai R, Venkateshwarlu V, Harisudhan T. Development and characterization of solid oral dosage form incorporating candesartan nanoparticles. Pharm Dev Technol. 2009;14(3):290–8.

    Article  CAS  PubMed  Google Scholar 

  39. Vijaykumar N, Venkateswarlu V, Raviraj P. Development of oral tablet dosage form incorporating drug nanoparticles. Res J Pharm Biol Chem Sci. 2010;1:952–63.

    CAS  Google Scholar 

  40. Nekkanti V, Pillai R, Vabalaboina V. Drug nanoparticles-an overview: INTECH Open Access Publisher; 2012.

  41. Kerker M. The scattering of light and other electromagnetic radiation: physical chemistry: a series of monographs. New York: Academic Press; 2013.

  42. Nekkanti V, Venkateswarlu V, Harisudhan T, Pillai R. Development and characterization of solid dosage form incorporating camptothecin analog nanoparticles. Inventi Impact: Pharm Tech. 2010; 1(2).

  43. Hunter RJ. Zeta potential in colloid science: principles and applications. New York: Academic Press; 2013.

  44. Böhm BH, Müller RH. Lab-scale production unit design for nanosuspensions of sparingly soluble cytotoxic drugs. Pharm Sci Technol Today. 1999;2(8):336–9.

    Article  PubMed  Google Scholar 

  45. Cetin M, Atila A, Kadioglu Y. Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. Aaps Pharmscitech. 2010;11(3):1250–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Heng D, Cutler DJ, Chan H-K, Yun J, Raper JA. What is a suitable dissolution method for drug nanoparticles? Pharm Res. 2008;25(7):1696–701.

    Article  CAS  PubMed  Google Scholar 

  47. Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, et al. Development of novel cationic chitosan-and anionic alginate-coated poly (D, L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol. Int J Nanomedicine. 2012;7:5501.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O, et al. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release. 2009;133(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  49. Wallace SJ, Li J, Nation RL, Boyd BJ. Drug release from nanomedicines: selection of appropriate encapsulation and release methodology. Drug Deliv Transl Res. 2012;2(4):284–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Juenemann D, Jantratid E, Wagner C, Reppas C, Vertzoni M, Dressman JB. Biorelevant in vitro dissolution testing of products containing micronized or nanosized fenofibrate with a view to predicting plasma profiles. Eur J Pharm Biopharm. 2011;77(2):257–64.

    Article  CAS  PubMed  Google Scholar 

  51. Sievens-Figueroa L, Pandya N, Bhakay A, Keyvan G, Michniak-Kohn B, Bilgili E, et al. Using USP I and USP IV for discriminating dissolution rates of nano-and microparticle-loaded pharmaceutical strip-films. Aaps Pharmscitech. 2012;13(4):1473–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chidambaram N, Burgess D. A novel in vitro release method for submicron-sized dispersed systems. AAPS PharmSci. 1999;1(3):32–40.

    Article  PubMed Central  Google Scholar 

  53. Calvo P, Vila‐Jato JL, Alonso MJ. Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules, and nanoemulsions, as ocular drug carriers. J Pharm Sci. 1996;85(5):530–6.

    Article  CAS  PubMed  Google Scholar 

  54. Tan JP, Goh CH, Tam KC. Comparative drug release studies of two cationic drugs from pH-responsive nanogels. Eur J Pharm Sci. 2007;32(4):340–8.

    Article  CAS  PubMed  Google Scholar 

  55. Rosenblatt KM, Douroumis D, Bunjes H. Drug release from differently structured monoolein/poloxamer nanodispersions studied with differential pulse polarography and ultrafiltration at low pressure. J Pharm Sci. 2007;96(6):1564–75.

    Article  CAS  PubMed  Google Scholar 

  56. Charalampopoulos N, Avgoustakis K, Kontoyannis CG. Differential pulse polarography: a suitable technique for monitoring drug release from polymeric nanoparticle dispersions. Anal Chim Acta. 2003;491(1):57–62.

    Article  CAS  Google Scholar 

  57. Kayaert P, Li B, Jimidar I, Rombaut P, Ahssini F, Van den Mooter G. Solution calorimetry as an alternative approach for dissolution testing of nanosuspensions. Eur J Pharm Biopharm. 2010;76(3):507–13.

    Article  CAS  PubMed  Google Scholar 

  58. Helle A, Hirsjärvi S, Peltonen L, Hirvonen J, Wiedmer SK, Hyötyläinen T. Novel, dynamic on-line analytical separation system for dissolution of drugs from poly (lactic acid) nanoparticles. J Pharm Biomed Anal. 2010;51(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  59. Borkar N, Xia D, Holm R, Gan Y, Müllertz A, Yang M, et al. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium. Eur J Pharm Sci. 2014;51:204–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, India

    Sandeep Kalepu

  2. College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA

    Vijaykumar Nekkanti

Authors
  1. Sandeep Kalepu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vijaykumar Nekkanti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandeep Kalepu.

Ethics declarations

Conflict of interest

The author(s) confirm that this article content has no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalepu, S., Nekkanti, V. Improved delivery of poorly soluble compounds using nanoparticle technology: a review. Drug Deliv. and Transl. Res. 6, 319–332 (2016). https://doi.org/10.1007/s13346-016-0283-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-016-0283-1

Keywords

Search

Navigation