A REVIEW ON THE ROLE OF NANOCRYSTALS AND NANOSUSPENSIONS IN DRUG DELIVERY SYSTEMS

  • S. J. SHANKAR Department of Pharmaceutics, Vivekananda College of Pharmacy, Dr. Rajkumar Road, Rajajinagar 2nd Stage, Bengaluru 560055
  • JASWANTH GOWDA B. H. Department of Pharmaceutics, Vivekananda College of Pharmacy, Dr. Rajkumar Road, Rajajinagar 2nd Stage, Bengaluru 560055
  • AKSHATHA R. S. Department of Pharmaceutics, PES College of Pharmacy, PES University, 50 Feet Road, Hanumanthnagar, Bengaluru 560050
  • BASAVARAJ METIKURKI Department of Pharmaceutical Chemistry, Nitte College of Pharmaceutical Sciences, NMIT Campus, Yelahanka, Bengaluru 560064
  • MOHAMED REHAMATHULLA Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Asir Provience, Saudi Arabia, Post Box No–960

Abstract

Nearly 40% of drugs coming to the market nowadays are having poor solvency related issues and 70% molecules in discovery pipeline are in effect fundamentally insoluble in water. Nanocrystals is an unmistakable instrument to tackle the issue identified with poor fluid solvency and helps in improving the bioavailability of various drugs as presented in the literature. The particle size reduction came about into temperamental nanocrystalline system and the phenomenon of ostawald ripening happens. These techniques are preparing to the improvement of nanosized objects, which can play out multiple technological tasks. There are a few couples of noteworthy benefits of nanocrystal formulations, for example, upgrade oral bioavailability, improved dose proportionality, reduced food effects, appropriateness for administration by all routes and probability of sterile filtration because of diminished particle size range. One of the most adequate preferences of nanocrystals is their wide scope of utilization, for example, ophthalmic delivery, oral delivery, transdermal delivery, pulmonary delivery, intravenous delivery and targeted delivery, especially for tumour and brain. The increment in commercial value of nanocrystals just as the measure of nanocrystal products in the market is picking up more of attention to be utilized as a strategy so as to get commercial advantages. In this paper a brief and accurate precis of nanosuspension is stated with specific spotlight on nanosuspension preparation methodologies, benefits and few major applications of nanosuspensions.

Keywords: Nanocrystal, Nanosuspension, Bioavailability, Solubility, Media milling, Dissolution rate, Bottom up approach, High pressure homogenization

References

1. Chan VS. Nanomedicine: an unresolved regulatory issue. Regul Toxicol Pharmacol 2006;46:218-24.
2. Liversidge ME, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poor-water soluble compounds. Eur J Pharm Sci 2003;18:113-20.
3. Freitas RA. What is nanomedicine? Nanomedicine 2005;1:2-9.
4. Keck CM, Muller RH. Drug nanocrystals of poorly soluble drugs produced by high-pressure homogenisation. Eur J Pharm Biopharm 2006;62:3-16.
5. Shegokar R, Muller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm 2010;399:129-39.
6. Butler JM, Dressman JB. The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci 2010;99:4940-54.
7. Moschwitzer JP. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm 2013;453:142-56.
8. Lipinski CA. Drug-like properties and the causes of poor solubility. J Pharmacol Toxicol Methods 2000;44:235-49.
9. Bevernage J, Brouwers J, Brewster ME, Augustijns P. Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues. Int J Pharm 2013;453:25-35.
10. Dave RH, Shah DA, Patel PG. Development and evaluation of high loading oral dissolving film of aspirin and acetaminophen. J Pharm Sci Pharmacol 2014;1:112-22.
11. Cooper ER. Nanoparticles: a personal experience for formulating poorly water soluble drugs. J Controlled Release 2010;141:300-2.
12. Sigfridsson K, Lundqvist AJ, Strimfors M. Size reduction for improvement of oral absorption of the poorly soluble drug UG558 in rats during early development. Drug Dev Ind Pharm 2009;35:1479-86.
13. 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.
14. Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystallinedanazol in beagle dogs. Int J Pharm 1995;125:91-7.
15. Kesisoglou F, Panmai S, Wu Y. Nanosizing–oral formulation development and biopharmaceutical evaluation. Adv Drug Delivery Rev 2007;59:631-44.
16. Murdande SB, Pikal MJ, Shanker RM, Bogner RH. Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis. J Pharm Sci 2010;99:1254-64.
17. Murdande SB, Pikal MJ, Shanker RM, Bogner RH. Solubility advantage of amorphous pharmaceuticals: II. Application of quantitative thermodynamic relationships for prediction of solubility enhancement in structurally diverse insoluble pharmaceuticals. Pharm Res 2010;27:2704-14.
18. Liu G, Zhang D, Jiao Y, Guo H, Zheng D, Jia L, et al. In vitro and in vivo evaluation of riccardin D nanosuspensions with different particle size. Colloids Surf B 2013;102:620-6.
19. Detroja C, Chavhan S, Sawant K. Enhanced antihypertensive activity of candesartan cilexetil nanosuspension: formulation, characterization and pharmacodynamic study. Sci Pharm 2011;79:635-51.
20. Hecq J, Deleers M, Fanara D, Vranckx H, Amighi K. Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. Int J Pharm 2005;299:167-77.
21. Schmelzer JW, Schmelzer J. Kinetics of nucleation at increasing supersaturation. J Colloid Interface Sci 1999;215:345-55.
22. Shah KB, Patel PG, Khairuzzaman A, Bellantone RA. An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD). Int J Pharm 2014;468:64-74.
23. Cheow WS, Hadinoto K. Self-assembled amorphous drug–polyelectrolyte nanoparticle complex with enhanced dissolution rate and saturation solubility. J Colloid Interface Sci 2012;367:518-26.
24. Eerdenbrugh VB, Vermant J, Martens JA, Froyen L, Humbeeck JV, Mooter VDG, et al. Solubility increases associated with crystalline drug nanoparticles: methodologies and significance. Mol Pharm 2010;7:1858-70.
25. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev 2013;65:315-499.
26. Sun B, Yeo Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr Opin Solid State Mater Sci 2012;16:295-301.
27. Barret ER. Nanosuspensions in drug delivery. Nat Rev Drug Discovery 2004;3:785-96.
28. Nanosuspension Systems. Hamamatsu Nano technology. Available from: http://www.hamanano.com/e/products/C3/C3_1/. [Last accessed on 10 Jul 2019]
29. Raval JA, Patel JK, Patel MM. Nanosuspensions as particulate drug delivery systems.?Pharm Rev 2006;4:5.
30. Prabhakar C, Krishna BK. A review on nanosuspensions in drug delivery. Int J Pharma Bio Sci 2011;2:549-58.
31. Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discovery 2004;3:785-96.
32. Liu P, Rong X, Laru J. Nanosuspensions of poorly soluble drugs: preparation and development by wet milling. Int J Pharm 2011;411:215-22.
33. Ibrahim HM, Ismail HR, Lila AEA. Formulation and optimization of ocular poly-D, L-lactic acid nano-drug delivery system of amphotericin-B using box behnken design. Int J Pharm Pharm Sci 2012;4:342-9.
34. Sutradhar KB, Khatun S, Luna IP. Increasing possibilities of nanosuspension. J Nanotechnol 2013. http://dx.doi.org/ 10.1155/2013/346581.
35. Arole VM, Munde SV. Fabrication of nanomaterials by top-down and bottom-up approaches–an overview. J Adv Appl Sci Technol 2014;1:89-93.
36. Salazar J, Muller RH, Moschwitzer JP. Combinative particle size reduction € technologies for the production of drug nanocrystals. J Pharm 2014;14. http://dx.doi.org/10.1155/ 2014/265754.
37. Weber U. The effect of grinding media performance on milling a water-based color pigment. Chem Eng Technol 2010;33:1456-63.
38. Singh SK, Srinivasan KK, Gowthamarajan K, Singare DS, Prakash D, Gaikwad NB. Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide. Eur J Pharm Biopharm 2011;78:441-6.
39. Tashan E, Karakucuk A, Celebi N. Optimization and in vitro evaluation of ziprasidone nanosuspensions produced by a top-down approach. J Drug Delivery Sci Technol 2019;52:37-45.
40. Guo L, Kang L, Liu X, Lin X, Di D, Wu Y, et al. A novel nanosuspension of Andrographolide: preparation, characterization and passive liver target evaluation in rats. Eur J Pharm Sci 2017;104:13-22.
41. Shen C, Shen B, Liu X, Yuan H. Nanosuspensions based gel as the delivery system of nitrofurazone for enhanced dermal bioavailability. J Drug Delivery Sci Technol 2018;43:1-11.
42. Huang S, Zhang Q, Li H, Sun Y, Cheng G, Zou M, et al. Increased bioavailability of efonidipine hydrochloride nanosuspensions by the wet-milling method. Eur J Pharm Biopharm 2018;130:108-14.
43. Malamatari M, Taylor KMG, Malamataris S, Douroumis D, Kachrimanis K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discovery Today 2018;23:534-47.
44. Reddy GA, Anilchowdary Y. Nanosuspension technology: a review. J Pharm Cosmetol 2012;2:47-52.
45. Wang H, Xiao Y, Wang H, Sang Z, Han X, Ren S, et al. Development of daidzein nanosuspensions: preparation, characterization, in vitro evaluation, and pharmacokinetic analysis. Int J Pharm 2019;566:67-76.
46. Karakucuk A, Teksin ZS, Eroglu H, Celebi N. Evaluation of improved oral bioavailability of ritonavir nanosuspension. Eur J Pharm Sci 2019;131:153-8.
47. Nagaraju P, Krishnachaithanya K, Srinivas VDN, Padma SVN. Nanosuspensions: promising drug delivery systems. Int J Pharm Sci Nanotechnol 2010;2:679-84.
48. Sumathi R, Tamizharasi S, Sivakumar T. Formulation and evaluation of polymeric nanosuspension of naringenin. Int J Appl Pharm 2017;9:60-70.
49. https://www.researchgate.net/figure/Schematic-diagram-of-the-process-of-high-pressure-homogenization-21_fig.2_280444393. [Last accessed on 10 Jul 2019]
50. Kathpalia H, Juvekar S, Shidhaye S. Design and in vitro evaluation of atovaquone nanosuspension prepared by ph based and anti-solvent based precipitation method. J Colloid Interface Sci 2019;29:26-32.
51. Santos DAM, Carvalho FC, Teixeira DA, Azevedo DL, Barros WMD, Gremiao MPD. Computational and experimental approaches for the development of methotrexate nanosuspensions by bottom-up nanoprecipitation. Int J Pharm 2017;524:330-8.
52. Shariare MH, Altamimi MA, Marzan AL, Tabassum R, Jahan B, Reza HM, et al. In vitro dissolution and bioavailability study of furosemide nanosuspension prepared using a design of experiment (DoE). Saudi Pharm J 2018;27:96-105.
53. He S, Yang H, Zhang R, Li Y, Duan L. Preparation and in vitro-in vivo evaluation of teniposide nanosuspensions. Int J Pharm 2014;478:131-7.
54. Mishra B, Sahoo J, Dixit PK. Formulation and process optimization of naproxen nanosuspensions stabilized by hydroxyl propyl methylcellulose. Carbohydr Polym 2015;127:300-8.
55. Manishaanjane, Agrawal S, Khan A. Formulation and evaluation of nanosuspension of valsartan. Int J Curr Pharm Res 2018;10:68-74.
56. Dekate S, Bhairy S, Hirlekar R. Preparation and characterization of oral nanosuspension loaded with curcumin. Int J Pharm Pharm Sci 2018;10:90-5.
57. Paun JS. Nanosuspension: an emerging trend for bioavailability enhancement of poorly soluble drugs. Asian J Pharm Tech 2012;2:157-68.
58. Vaghela A. Nanosuspension technology. Int J Universal Pharm Life Sci 2012;2:306-17.
59. Bhargavi R. Technical review of nanosuspensions. Int J Pharm Technol 2011;3:1503-11.
60. Verma KAK. Nanosuspensions: advantages and disadvantages. Indian J Novel Drug Delivery 2012;4:179-88.
61. Rao SK, Prasad T, Mohanta GP, Manna PK. An overview of statins as hypolipidemic drugs. Int J Pharm Sci Drug Res 2011;3:178-83.
62. Boedeker BH, Lojeski EW, Kline MD, Haynes DH. Ultra-long duration local anesthesia produced by injection of lecithin-coated tetracaine microcrystals. J Clin Pharmacol 1994;34:699-702.
63. Jia L, Wong H, Cerna C, Weitman SD. Effect of nanonization on absorption of 301029:Ex vivo and in vivo pharmacokinetic correlations determined by liquid chromatography/mass spectrometry. Pharm Res 2002;19:1091-6.
64. Liversidge ME. Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs. Pharm Res 1996;13:272-8.
65. Peters K, Leitzke S, Diederichs JE, Borner K, Hahn H, Muller RH, et al. Preparation of a clofazamine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. J Antimicrob Chemother 2000;45:77-83.
66. Rainbow B, Kipp J, Papadopoulos P, Wong J, Glosson J, Gass J, et al. Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int J Pharm 2007;339:251-60.
67. Trejo HN, Kayser O, Steckel H, Muller RH. Characterization of nebulized bupravaquone nanosuspensions-effect of nebulization technology. J Drug Target 2005;13:499-507.
68. Mansour HM, Rhee YS, Wu X. Nanomedicine in pulmonary delivery. Int J Nanomed 2009;4:299-319.
69. Aher SS, Malsane ST, Saudagar RB. Nanosuspension: an overview. Int J Curr Pharm Res 2017;9:19-23.
70. Liang Y, Binner J. Effect of triblock copolymer non-ionic surfactants on the rheology of 3 mol% yttria-stabilized zirconia nanosuspensions. Ceram Int 2008;34:293-7.
71. Kayser O, Lemke A, Trejo HN. The impact of nanobiotechnology on the development of new drug delivery systems. Curr Pharm Biotechnol 2005;6:3-5.
72. Kayser O. Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against leishmania infected macrophages. Int J Pharm 2000;196:253-6.
73. Scholer N, Krause K, Kayser O, Moller RH, Borner K, Hahn H, et al. Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother 2001;45:1771-9.
74. Du J, Li X, Zhao H, Zhou Y, Wang L, Tian S, et al. Nanosuspensions of poorly water-soluble drugs prepared by bottom-up technologies. Int J Pharm 2015;495:738-49.
75. Lakshmi P, Kumar GA. Nano-suspension technology: a review. Int J Pharm Pharm Sci 2010;2:35-40.
Statistics
358 Views | 336 Downloads
Citatons
How to Cite
SHANKAR, S. J., B. H., J. G., R. S., A., METIKURKI, B., & REHAMATHULLA, M. (2019). A REVIEW ON THE ROLE OF NANOCRYSTALS AND NANOSUSPENSIONS IN DRUG DELIVERY SYSTEMS. International Journal of Applied Pharmaceutics, 12(1), 10-16. https://doi.org/10.22159/ijap.2020v12i1.35508
Section
Review Article(s)