NANOCRYSTALS: A TOOL FOR ENHANCING DRUG DISSOLUTION
Main Article Content
Keywords
Nanocrystals, Dissolution, Stabilizers and Bioavailability
Abstract
Poor aqueous solubility is a significant challenge in the formulation and delivery of many pharmaceutical compounds, leading to suboptimal bioavailability and therapeutic efficacy. Nanocrystals have emerged as a promising approach to address this issue by enhancing drug dissolution and improving drug delivery systems. This review provides an in-depth analysis of the role of nanocrystals in enhancing drug dissolution and their potential as a tool for improving drug formulations and explaining the principles of nanocrystal technology, including the media milling, preparation method and homogenization method, and the use of stabilizers and surfactants to prevent aggregation. The applications of nanocrystals in different drug delivery systems are explored, including oral, parenteral, and topical routes. In conclusion, nanocrystals represent a powerful tool for enhancing drug dissolution and improving drug delivery systems for poorly water-soluble drugs. Their ability to enhance bioavailability and therapeutic efficacy holds great promise for advancing pharmaceutical development.
References
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31. Vishal V. Pande and Vidya N. Abhale Nanocrystal technology: A particle engineering formulation strategy for the poorly water soluble drugs Scholars Research Library 2016; 8 (5); 384-392.
32. Y. Wang, Y. Zheng, L. Zhang, Q. Wang, D. Zhang, Stability of nanosuspensions in drug delivery, J. Control. Release 172 (2013); 1126-1141.
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36. Dolenc, J. Kristl ,S.Baumgartner,O. Planinsek, Advantages of celecoxib Nanosuspension formulation and transformation into tablets, Int. J. Pharm. 376 (2009);204- 212.
37. D. Douroumis, A. Fahr, Stable carbamazepine colloidal systems using the cosolvent technique, Eur. J. Pharm. Sci. 30; (2007); 367-374.
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40. L. Gao, D. Zhang,M. Chen, T. Zheng, S.Wang, Preparation and characterization of anoridoninnanosuspension for solubility and dissolution velocity enhancement,Drug Dev. Ind. Pharm. 33; (2007); 1332- 1339.
41. Ghosh, S. Bose, R. Vippagunta, F. Harmon, Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibitcrystal growth, Int. J. Pharm. 409; (2011); 260-268.
42. Chen H, Khemtong C, Yang X, Chang X and Gao J, Nanonization strategies for poorly water soluble drugs, Drug Discovery Today, 2010;00:1-6.
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45. Kipp JE. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int J Pharm2004;284(1-2);109-122.
46. Jens-Uwe A H Junghanns and Rainer H Müller Nanocrystal technology, drug delivery and clinical applications Int J Nanomedicine. 2008 Sep; 3(3): 295±310.
47. Nanotax clinical trial. Kansas cancer treatmenthttp://www.kansascancertreatment.org/ (Accessed May 8, 2010).
48. Zolip 0502: Comparison of the combination of fenofibrate and 40mg simvastatin versus 40 mg simvastatin monotherapy; Solvay Pharmaceuticals. http://www.druglib.com/trial/83/NCT00352183 html (Accessed May 15, 2010).
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52. J.-J. Guo, P.-F. Yue, J.-l. Lv, J. Han, S.-S. Fu, S.-X. Jin, S.-Y. Jin, H.-L. Yuan, Developmentand in vivo/in vitro evaluation of novel herpetrione nanosuspension, Int. J. Pharm.441 (2013); 227±233.
53. Femia R. Megestrol acetate nanocrystal: Results of doseescalating studies under fed and fasting conditions. California, USA. 2005.
54. Müller RH and Jacobs C, Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability, Int. J. Pharm, 2002; 237: 151–161.
55. Hernandez-TrejoN, Kayser O, Steckel H and Muller RH, Characterization nebulized buparvaquone nanosuspensions effect of nebulization technology, J. Drug Target, 2005; 13: 499–507.
56. Bucolo C, Maltese A, Puglisi G and Pignatello R, Enhanced ocular anti-inflammatory activity of ibuprofen carried by an Eudragit RS100 nanoparticle suspension, Ophthalmic Res,2002; 34 : 319–323.
57. Katteboinaal S, Chandrasekhar P, Balaji S, Drug nanocrystals: a novel formulation approach for poorly soluble drugs, International Journal of PharmTech Research, 2009; 1(3): 682-694.
58. Kayser O, Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against Leishmania infected macrophages, International Journal of Pharmaceutics, 2000;196(2):253-25
2. Keck C, Kobierski S, Mauludin R, Müller RH, Second generation of drug nanocrystals for delivery of poorly soluble drugs: smart crystals technology,D O S I S,2008; 24(2):125-127.
3. Troester F, Cremophor-free aqueous paclitaxel nanosuspension—production and chemical stability, Controlled Release Society 31st annual meeting, Honolulu, HI, 2004.
4. Möschwitzer J, Achleitner G, Pomper H, Muller RH, Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology, European Journal of Pharmaceutics and Biopharmaceutics, 2004; 58(3):615–619.
5. Noyes,W. Whitney, The rate of solution of solid substances in their own solutions, J. Am. Chem. Soc. 19 (1897) 930–934.
6. V.B. Patravale, A.A. Date, R.M. Kulkarni, Nanosuspensions: a promising drug delivery strategy, J. Pharm. Pharmacol. 56 (7) (2004) 827–840.
7. Y. Wu, A. Loper, E. Landis, L. Hettrick, L. Novak, K. Lynn, C. Chen, K. Thompson, R. Higgins, U. Batra, S. Shelukar, G. Kwei, D. Storey, The role of biopharmaceutics in thedevelopment of a clinical nanoparticle formulation of MK-0869: a beagle dog model predicts.improved bioavailability and diminished food effect on absorption in human, Int. J. Pharm.285 (1– 2) (2004) 135–146.
8. M. Mosharraf, C. Nystrom, The effect of particle size and shape on the surface specific dissolution rate of micronized practically insoluble drugs, Int. J. Pharm. 122 (1995) 35– 47.
9. R.H. Muller, K. Peters, Nanosuspensions for the formulation of poorly soluble drugs I. Preparation by a size-reduction technique, Int. J. Pharm. 160 (1998) 229–237
10. Buchmann S, Fischli W, Thiel FP, Alex R. Aqueous microsuspension, an alternative intravenous formulation for animal studies. In: 42nd annual congress of the International Association for Pharmaceutical Technology (APV), Mainz, 1996.
11. Bruno JAD, Brian D. Gustow Evan, Illig, Kathleen J, Rajagopalan, Nats, Sarpotdar. Method of grinding pharmaceutical substances. US 5,518,187, 1992.
12. Wyeth Research Drug Information, Rapamune (Sirolumus) Oral Solutions and Tablets. Company Communications, 2004.
13. Merck, Drug Information Emend. 2004.
14. Speiser PP (1998) Poorly soluble drugs, a challenge in drug delivery, in Muller RH, Benita S and Bohm B (eds.), Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs, Medpharm Scientific Publishers: Stuttgart.
15. Bruno RPM (1999) Microfluidizer Processor Technology for High Performance Particle Size Reduction, Mixing and Dispersion. Microfluidizer Processor Technology.
16. Parikh IS, Ulagaraj Composition and method of preparing microparticles of waterinsoluble substances. 93969997, 1997
17. Haynes DH. Phospholipid-coated microcrystals: injectable formulations of waterinsoluble drugs. US 5,091,187,1992
18. Miiller RH, Jacobs C and Kayser O (2000) Nanosuspensions for the formulation of poorly soluble drugs, in Nielloud F and Marti-Mestres G (eds.) Pharmaceutical Emulsions and Suspensions, Marcel Dekker
19. Muller RH, Jacobs C and Kayser O (2003) DissoCubes — A novel formulation for poorly soluble and poorly bioavailable drugs, in Rathbone MJ, Hadgraft}, Roberts MS (eds.), Modified- Release Drug Delivery Systems, Marcel Dekker.
20. Radke M, Pure drug nanoparticles for formulation of poorly soluble drug, New drug delivery: www.pharmasol-berlin.de. Kipp JE, Tak Wong JC, Doty MJ, Rebbeck CL. US Pat. application no. 20020168402 A1.2002
21. Türk M, Hils P, Helfgen B, Schaber K, Martin HJ, Wahl MA, Micronization of pharmaceutical substances by Rapid Expansion of Supercritical Solutions (RESS): a promising method to improve the bioavailability of poorly soluble pharmaceutical agents, J Supercrit Fluids,2002:75–84.
22. Katteboinaal S, Chandrasekhar P, Balaji S, Drug nanocrystals: a novel formulation approach for poorly soluble drugs, International Journal of PharmTech Research, 2009; 1(3): 682-694.
23. Li Zhiyi, Preparation of griseofulvin microparticles by supercritical fluid expansion depressurization processPowderTechnology Volume 182, Issue 3, 10 March 2008, Pages 459-465.
24. Andrian Tandya, Micronization of cyclosporine using dense gas techniques, The Journal of SupercriticalFluids, Volume 37, Issue 3, May 2006, Pages 272-278.
25. Young, Phospholipid-Stabilized Nanoparticles of Cyclosporine A by Rapid Expansion from Supercritical to Aqueous Solution AAPS PharmSciTech 2003; 5 (1) Article 11.
26. Physical stability of micronized powders produced by spray-freezing into liquid (SFL) to enhance the dissolution of an insoluble drug. Rogers TL, Johnston KP, Williams RO 3rd. Pharm Dev Technol. 2003;8(2):187-97.
27. Böhm B. Production and characterisation of nanosuspensions as novel delivery system for drugs with low bioavailability. In: Pharmaceutical Technology. Berlin: Free University of Berlin, 1999.
28. Merisko-Liversidge E, Liversidge GG, Cooper ER, Nanosizing: A Formulation Approach for Poorly-Water-Soluble Compounds, Eur J PharmSci.2003; 18: 113-120.
29. Kesisoglou F, Panmai S, Wu Y, Nanosizing– Oral formulation development and biopharmaceutical evaluation, Adv Drug DelivRev,2007;59: 631–644.
30. Gao L., Zhang D. et al, Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system, J Nanopart Res.2008; 10: 845- 862.
31. Vishal V. Pande and Vidya N. Abhale Nanocrystal technology: A particle engineering formulation strategy for the poorly water soluble drugs Scholars Research Library 2016; 8 (5); 384-392.
32. Y. Wang, Y. Zheng, L. Zhang, Q. Wang, D. Zhang, Stability of nanosuspensions in drug delivery, J. Control. Release 172 (2013); 1126-1141.
33. J. Deng, L. Huang, F. Liu, Understanding the structure and stability of paclitaxel Nanocrystals, Int. J. Pharm. 390 (2010); 242-249.
34. Vivek K. Pawar, Yuvraj Singh, Jaya Gopal Meher, Siddharth Gupta, Manish K. Chourasia Engineered nanocrystal technology: In-vivo fate, targeting and applications in drug delivery, Journal of Controlled Release 183:(2014):51-66.
35. Pongpeerapat, C. Wanawongthai, Y. Tozuka, K. Moribe, K. Yamamoto, Formation mechanism of colloidal nanoparticles obtained from probucol/PVP/SDS ternary ground mixture, Int. J. Pharm. 352; (2008); 309-316.
36. Dolenc, J. Kristl ,S.Baumgartner,O. Planinsek, Advantages of celecoxib Nanosuspension formulation and transformation into tablets, Int. J. Pharm. 376 (2009);204- 212.
37. D. Douroumis, A. Fahr, Stable carbamazepine colloidal systems using the cosolvent technique, Eur. J. Pharm. Sci. 30; (2007); 367-374.
38. R.C. Rowe, P.J. Sheskey, S.C. Owen, Handbook of Pharmaceutical Excipients,Pharmaceutical Press, London, 2006
39. J. Lee, S.-J. Lee, J.-Y. Choi, J.Y. Yoo, C.-H. Ahn, Amphiphilic amino acid copolymers asstabilizers for the preparation of nanocrystal dispersion, Eur. J. Pharm. Sci. 24(2005); 441-449
40. L. Gao, D. Zhang,M. Chen, T. Zheng, S.Wang, Preparation and characterization of anoridoninnanosuspension for solubility and dissolution velocity enhancement,Drug Dev. Ind. Pharm. 33; (2007); 1332- 1339.
41. Ghosh, S. Bose, R. Vippagunta, F. Harmon, Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibitcrystal growth, Int. J. Pharm. 409; (2011); 260-268.
42. Chen H, Khemtong C, Yang X, Chang X and Gao J, Nanonization strategies for poorly water soluble drugs, Drug Discovery Today, 2010;00:1-6.
43. A.H. Shojaei, Buccal mucosa as a route for systemic drug delivery: a review, J.Pharm. Pharm. Sci. 1 (1998); 15±30.
44. Hanafy A, Spahn H, Vergnaut G, Grenier p, GrozdanisMT,Lenhardt T, Pharmacokinetic evaluation of oral fenofibrate and nonosuspension and SLN in comparision with conventional suspension of micronized drug. Adv Drug Del Rev 2007;19-26.
45. Kipp JE. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int J Pharm2004;284(1-2);109-122.
46. Jens-Uwe A H Junghanns and Rainer H Müller Nanocrystal technology, drug delivery and clinical applications Int J Nanomedicine. 2008 Sep; 3(3): 295±310.
47. Nanotax clinical trial. Kansas cancer treatmenthttp://www.kansascancertreatment.org/ (Accessed May 8, 2010).
48. Zolip 0502: Comparison of the combination of fenofibrate and 40mg simvastatin versus 40 mg simvastatin monotherapy; Solvay Pharmaceuticals. http://www.druglib.com/trial/83/NCT00352183 html (Accessed May 15, 2010).
49. Tibotec Pharmaceuticals Submits New Drug Application for Investigational Once Daily HIV Treatment TMC278 to U.S. Food and Drug Administration. http://www.jnj.com/connect/news/product/ Tibotec-Pharmaceuticals-Submits-New-Drug-Application-for-Investigational-Once-Daily-HIV-Treatment-TMC278-to-US-Foodand-Drug-Administration (Accessed December 10, 210).
50. Life sciences news brief. http://www.biopharm.org.tw/ ic/ Canada/strategies (Accessed May 15, 2010).
51. Nanotechnology may deliver once-daily dosage of clozapine. Drug discovery & development. once-daily dosage of clozapine. Drug http://www.dddmag.com/news-once-daily-dosing-Clozapine.aspx (Accessed November 30, 2010).
52. J.-J. Guo, P.-F. Yue, J.-l. Lv, J. Han, S.-S. Fu, S.-X. Jin, S.-Y. Jin, H.-L. Yuan, Developmentand in vivo/in vitro evaluation of novel herpetrione nanosuspension, Int. J. Pharm.441 (2013); 227±233.
53. Femia R. Megestrol acetate nanocrystal: Results of doseescalating studies under fed and fasting conditions. California, USA. 2005.
54. Müller RH and Jacobs C, Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability, Int. J. Pharm, 2002; 237: 151–161.
55. Hernandez-TrejoN, Kayser O, Steckel H and Muller RH, Characterization nebulized buparvaquone nanosuspensions effect of nebulization technology, J. Drug Target, 2005; 13: 499–507.
56. Bucolo C, Maltese A, Puglisi G and Pignatello R, Enhanced ocular anti-inflammatory activity of ibuprofen carried by an Eudragit RS100 nanoparticle suspension, Ophthalmic Res,2002; 34 : 319–323.
57. Katteboinaal S, Chandrasekhar P, Balaji S, Drug nanocrystals: a novel formulation approach for poorly soluble drugs, International Journal of PharmTech Research, 2009; 1(3): 682-694.
58. Kayser O, Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against Leishmania infected macrophages, International Journal of Pharmaceutics, 2000;196(2):253-25
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Mar 19, 2023
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Sadhu Venkateswara Rao, Gopu Navyatha, Parakat Tanmai Meenakshi, Akunuri Sai Divya, Chandolu Lakshmi Akhila Jahnavi, & Kantamneni Padmalatha. (2023). NANOCRYSTALS: A TOOL FOR ENHANCING DRUG DISSOLUTION. Journal of Population Therapeutics and Clinical Pharmacology, 30(4), 839-855. https://doi.org/10.53555/jptcp.v30i4.3171
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Author Biographies
Sadhu Venkateswara Rao
Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
Gopu Navyatha
Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
Parakat Tanmai Meenakshi
Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
Akunuri Sai Divya
Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
Chandolu Lakshmi Akhila Jahnavi
Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
Kantamneni Padmalatha
Department of Pharmacology, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh-521102, India.
How to Cite
Sadhu Venkateswara Rao, Gopu Navyatha, Parakat Tanmai Meenakshi, Akunuri Sai Divya, Chandolu Lakshmi Akhila Jahnavi, & Kantamneni Padmalatha. (2023). NANOCRYSTALS: A TOOL FOR ENHANCING DRUG DISSOLUTION. Journal of Population Therapeutics and Clinical Pharmacology, 30(4), 839-855. https://doi.org/10.53555/jptcp.v30i4.3171