Nanosuspensions: Recent Patents and Pharmaceutical Aspects as Drug Delivery Systems
DOI:
https://doi.org/10.37285/ijpsn.2017.10.2.1Abstract
Solubility is an essential factor for drug effectiveness, independent of the route of administration. Poorly soluble drugs are often a challenging task for formulators in the industry. Conventional approaches for enhancement of solubility have limited applicability, especially when the drugs are poorly soluble simultaneously in aqueous and in non-aqueous media. Nanosuspension technology can be used to improve the stability as well as the bioavailability of poorly soluble drugs. Nanosuspensions are biphasic systems consisting of pure drug particles dispersed in an aqueous vehicle, stabilized by surfactants. These are simple to prepare and are more advantageous than other approaches. Techniques such as wet milling, high-pressure homogenization, emulsification–solvent evaporation and super critical fluid have been used in the preparation of nanosuspensions. It has the advantage of delivery by various routes, including oral, parenteral, pulmonary and ocular routes. The present article reviews the current methods used to prepare nanosuspensions and their application in drug delivery. More than 100 patents have been published on nanosuspensions in the recent days. This patent reviews covers different methods of pharmaceutical preparation and applications in drug delivery as well as the recent marketed published or granted patent surveys. This patent review is useful in enhanceing the knowledge of pharmaceutical application in drug delivery.
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Keywords:
Nanosuspension, Disperse system, Stability, Solubility enhancement, Homogenization, Patent
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Published
2017-03-31
How to Cite
1.
Gharge VS, Shinde MB, Pustake BD, Kinage KB, Kulkarni AA. Nanosuspensions: Recent Patents and Pharmaceutical Aspects as Drug Delivery Systems. Scopus Indexed [Internet]. 2017 Mar. 31 [cited 2024 Nov. 19];10(2):3631-44. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/831
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Review Articles
References
(2013). Preparation and optimization of acetaminophen nanosuspension through nanoprecipitation using microfluidic devices an artificial neural networks study. Pharm Dev Technol 18: 609-618.
Ali HS, York P, and Blagden N (2009). Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors. Int J Pharm 375: 107-113.
Ankit V, Mahavir J, Hardik L and Praful B (2012). Nanosuspension technology. Int J Univ Pharm Life Sci 2(2): 306-17.
Bhowmik D, Harish G, Duraivel S and Kumar BP (2012). Nanosuspension-A novel approach in drug delivery system. J Pharma Innov 1(12): 50-63.
Chan VSW (2006). Nanomedicine: an unresolved regulatory issue. Regulatory Toxicology and Pharmacology 46: 3218-224.
Chen H, Wan J, Wang Y, Mou D, Liu H, Xu H, and Yang XA (2008). Facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid–base neutralization reactions. Nanotechnology 19: 375-378.
Chen X, Yong TJ, Sarkari M, Williams RO III and Johnston KP (2002). Preparation of cyclosporine nanoparticles by evaporative precipitation into aqueous solution. Int J Pharm 242: 3-14.
Cheng X, Li X and Wang Y. (2010). Taxol nanosuspension and preparation method thereof. CN201010174294.
Chiang PC, Alsup JW, Lai Y, Hu Y, Heyde BR, and Tung D (2009). Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery. Nanoscale Res Lett 4: 254-261.
Chingunpituk J. (2007). Nanosuspension technology for drug delivery. Walailak Journal of Science & Technology 4(2): 139-153.
Detroja C, Chavhan S, and Sawant K (2011). Enhanced antihypertensive activity of candesartan cilexetil nanosuspension formulation characterization and pharmacodynamic study. Sci Pharm 79: 635-651.
Dohrn R, Bertakis E, Behrend O, Voutsas E and Tassios D (2007). Melting point depression by using supercritical CO2 for a novel melt dipersion micronization process. J Mole Liq 131-132: 53-9.
Dolenc A, Kristl J, Baumgartner S, and Planinsek O (2009). Advantages of celecoxib nanosuspension formulation and transformation into tablets. Int J Pharm 376: 204-212.
Dong LC, Wong PSL and Zhao R. (2004). Formulation and dosage form providing increased bioavailability of hydrophobic drugs. US20040142040A1.
Eerdenbrugh BV, Froyen L, Humbeeck JV, Martens JA, Augustijns P and Mooter GVD (2008). Alternative matrix formers for nanosuspension solidification Dissolution performance and X-ray microanalysis as an evaluation tool for powder dispersion. Eur J Pharm Sci 35: 344-353.
Freitas RA. (2005). What is nanomedicine? Nanomedicine 1(1): 2–9.
Gao L, Liu G, Wang X, Liu F, Xu Y and Ma J (2011). Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm 404: 231-237.
Gao Y, Li Z, Sun M, Guo C, Yu A, Xi Y, Cui J, Lou H and Zhai G (2011). Preparation and characterization of intravenously injectable curcumin nanosuspension. Drug Deliv 18: 131-142.
Gao YA, Qian SA and Zhang JJ (2010). Physicochemical and Pharmacokinetic Characterization of a Spray-Dried Cefpodoxime Proxetil Nanosuspension. Chem Pharm Bull 58: 912-917.
Ghosh I, Bose S, Vippagunta R and Harmon F (2011). Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int J Pharm 409: 260-268.
Hanafy A, Spahn-Langguth H, Vergnault G, Grenier P, Grozdanis MT and Lenhardt T (2007). Pharmacokinetic evaluation of oral fenofibrate nanosuspension and SLN in comparison to conventional suspensions of micronized drug. Adv Drug Deliv Rev 59: 419-26.
Hao LL, Wang XY, Zhang DR, Xu QY, Song SY, Wang FH, Li CY, Guo HJ, Liu Y, Zheng DD and Zhang Q (2012). Studies on the preparation, characterization and pharmacokinetics of Amoitone B nanocrystals. Int J Pharm 433: 157-164.
Homar M, Cegnar M, Lovse BE, Peternel L and Kerc J. (2011). An aqueous intravenous nanosuspension with reduced adverse effects. WO2011080148.
Horn D and Rieger J (2001). Organic nanoparticles in the aqueous phase—theory experiment and use. Angew Chem Int Ed Engl 40: 4330-4361.
Ibrahim HM, Ismail Lila HR and AEA (2012). Formulation and optimization of ocular poly-D, L-lactic acid nano drug delivery system of amphotericin-B using box behnken design. International Journal of Pharmacy and Pharmaceutical Sciences 4(2): 342–349.
Itoh K, Pongpeerapat A, Tozuka Y, Oguchi T and Yamamoto K (2003). Nanoparticle formation of poorly water soluble drugs from ternary ground mixtures with PVP and SDS. Chem Pharm Bull 51: 171-4.
Jacobs C, Kayser O and Muller RH (2001). Production and characterization of mucoadhesive nanosuspensions for the formulation of bupravaquone. Int J Pharm 214: 3-7.
Kayser O, Olbrich C, Yardley V, Kiderlen AF and Croft SL (2003). Formulation of amphotericin B as nanosuspension for oral administration. Int J Pharm 254: 73-5.
Kocbek P, Baumgartner S and Kristl J (2006). Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drug. Int J Pharm 312: 179-86.
Kohno S, Otsubo T, Tanaka E, Maruyama K and Hara K (1997). Amphotericin B encapsulated in polyethylene glycol immunoliposomes for infectious diseases. Adv Drug Dev Rev 24: 325-9.
Kondo M, Niwa T, Okamoto H, and Danjo K (2009). Particle characterization of poorly water-soluble drugs using a spray freeze drying technique. Chem Pharm Bull (Tokyo) 57: 657-662.
Kumar BS and Sabera K (2013). Increasing possibilities of nanosuspension. Hindawi Pub Corp J Nanotech 2: 1-13.
Kumar MP, Rao YM and Apte S (2007). Improved bioavailability of albendazole following oral administration of nanosuspension in rats. Curr Nanosci 3: 191-4.
Kumar N, Deecarman C and Mohanraj K (2009). Preparation and solid state characterization of atorvastatin nanosuspension for enhanced solubility and dissolution. International Journal of PharmTech Research 1725-1730.
Langguth P, Hanafy A, Frenzel D, Grenier P, Nhamias A and Ohlig T (2005). Nanosuspension formulations for low-soluble drugs: Pharmacokinetic evaluation using spironolactone as model compound. Drug Dev Ind Pharm 31: 319-29.
Liu F, Park JY, Zhang Y, Conwell C, Liu Y, Bathula SR and Huang L (2010). Targeted Cancer Therapy with Novel High Drug-Loading Nanocrystals. J Pharm Sci 99: 3542-3551.
Liversidge GG and Conzentino P (1995). Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats. Int J Pharm 125: 309-13.
Merisko-Liversidge E, Liversidge GG and Cooper ER (2003). Nanosizing: A formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci 18: 113-20.
Morrow KJ, Bawa R and Wei C (2007). Recent advances in basic and clinical nanomedicine. Medical Clinics of North America 91(5): 805–843.
Moschwitzer J, Achleitner G, Pomper H and Muller RH (2004). Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology. Eur J Pharm Biopharm 58: 615-619.
Muller RH, Becker R, Kruss B and Peters K (2004). Process for the preparation of pharmaceutical nanosuspensions. EP0790821.
Muller RH, Becker R, Kruss B and Peters K. (1996). Pharmaceutical nanosuspensions for medicament administration as systems with increased saturation solubility and speed of dissolution.WO1996014830.
Muller RH, Becker R, Kruss B and Peters K. (1999). Pharmaceutical nanosuspensions for medicament administration as systems with increased saturation solubility and rate of solution. US5858410
Muller RH and Jacobs C (2002). Buparvaquone mucoadhesive nanosuspension: Preparation, optimisation and longterm stability. Int J Pharm 237: 151-61.
Muller RH and Jacobs C (2002). Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharm Res 19: 189-94.
Müller RH, Jacobs C and Kayser O (2001). Nanosuspension as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Advanced Drug Delivery Reviews 47: 3-19.
Muller RH, Jacobs C, Kayser O, Rathbone MJ, Hadgraft J and Roberts MS (2003). Modified release drug delivery technology. New York Basel 135-49.
Mura P, Cirri M, Faucci MT, Gines-Dorado JM and Bettinetti GP (2002). Investigation of the effects of grinding and co-grinding on physicochemical properties of glisentide. J Pharm Biomed Anal 30: 227-37.
Mura P, Faucci MT and Bettinetti GP (2001). The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl- cyclodextrin. Eur J Pharm Sci 13: 187-94.
Nakach M (2012). High-pressure homogenization with a silicon nitride valve: US20120127823
Nakamoto K, Urasaki T, Hondo S, Murahashi N, Yonemochi E and Terada K (2013). Evaluation of the crystalline and amorphous states of drug products by nanothermal analysis and Raman imaging. J Pharmaceut Biomed 75: 105-111.
Otsuka M and Matsuda Y (1995). Effect of co-grinding with various kinds of surfactants on the dissolution behavior of phenytoin. J Pharm Sci 84: 1434-7.
Patravale VB, Date AA and Kulkarni RM (2004). Nanosuspensions a promising drug delivery strategy. J Pharm Pharmacol 56: 827-840.
Peters K, Leitzke S, Diederichs JE, Borner K and Hahn H (2000). Preparation of a clofazamine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine mycobacterium avium infection. J Antimicrob Chemother 45: 77-83.
Pintu KD and Subrata C (2012). Nanosuspensions: Potent vehicles for drug delivery and bioavailability enhancement of lipophilic drugs. J Pharm Res 5(3): 1548-54.
Prabhakar C and Krishna KB (2011). A review on nanosuspensions in drug delivery. International Journal of Pharma and Bio Sciences 2(1): 549-558.
Praveen K and Kotty GK (2011). Nanosuspensions: The solution to deliver hydrophobic drugs. Int J Drug Deliv 3: 546-57.
Puri V, Dantuluri AK, Kumar M, Karar N and Bansal AK (2010). Wettability and surface chemistry of crystalline and amorphous forms of a poorly water soluble drug. Eur J Pharm Sci 40: 84-93.
Rabinow BE (2004). Nanosuspensions in drug delivery. Nature Reviews Drug Discovery 3(9): 785-796.
Rabinow B, Kipp J, Papadopoulos P, Wong J, Glosson J and Gass J (2007). Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int J Pharm 339: 251-60.
Ramsden J. (2011). What is nanotechnology? In Nanotechnology: An Introduction, Elsevier, New York, NY, USA, pp. 1–14.
Reddy GA and Anilchowdary Y (2012). Nanosuspension technology: A review. J Pharmaceut Cosmet 2(8): 47-52.
Sahoo SK, Parveen S, and Panda JJ (2007). The present and future of nanotechnology in human health care. Nanomedicine 3(1): 20-31.
Sarkari M, Brown J, Chen X, Swinnea S, Williams RO III and Johnston KP (2002). Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm 243: 17-31.
Scholer N, Krause K, Kayser O, Müller RH, Borner K and Hahn H (2001). Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother 45: 1719.
Sudhir V and Diane B (2010). Solid nanosuspensions: The emerging technology and pharmaceutical applications as nanomedicine. Springer AAPS Press, 285-318.
Sugimoto M, Okagaki T, Narisawa S, Koida Y and Nakajima K (1998). Improvement of dissolution characteristics and bioavailability of poorly water-soluble drugs by novel co-grinding method using water soluble polymer. Int J Pharm 160: 9-11.
Trotta M, Gallarate M, Carlotti ME and Morel S (2003). Preparation of griseofulvin nanoparticles from water-dilutable micro-emulsions. Int J Pharm 254: 235-42.
Trotta M, Gallarete M, Pattarino F and Morel S (2001). Emulsions containing partially water-miscible solvents for the preparation of dry nanosuspensions. J Control Rel. 76: 119-28.
Van EB, Van den MG and Augustijns P. (2008). Top-down production of drug nanocrystals: Nanosuspension stabilization, miniturization and transformation into solid products. Int J Pharma. 364: 64-75.
Wang SL, Jiang TY, Sun CS and Ma Q. (2013). Valsartan spray dried nanosuspension and preparation method of valsartan spray-dried nanosuspension. CN102920654A.
Wang YL, Li XM, Wang LY, Xu YL, Cheng XD and Wei P (2011). Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery. Int J Nanomedicine 6: 1497-1507.
Watanabe T, Ohno I, Wakiyama N, Kusai A and Senna M (2002). Stabilization of amorphous indomethacin by co-grinding in a ternary mixture. Int J Pharm 241: 103-11.
Wong DH, Kim MS, Lee S, Jeong SP and Hwang SJ (2005). Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process. Int J Pharm 301: 199-208.
Xiaohai T, Yu Q and Lilin P. (2011). Lyophilized formulation of pectin adriamycin conjugate and preparation method thereof. WO2011134368A1.
Yonemochi E, Kitahara S, Maeda S, Yamamura S, Oguchi T and Yamamoto K (1999). Physicochemical properties of amorphous clarithromycin obtained by grinding and spray drying. Eur J Pharm Sci 7: 331-8.
Zhang D, Tan T, Gao L, Zhao W and Wang P (2007). Preparation of azithromycin nanosuspensions by high pressure homogenization and its physicochemical characteristics studies. Drug Dev Ind Pharm 33: 569-77.
Zhang X and Xia Q (2006). Preparation of all-trans retinoic acid nanosuspensions using a modified precipitation method. Drug Dev Ind Pharm 32: 857-63.
Ali HS, York P, and Blagden N (2009). Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors. Int J Pharm 375: 107-113.
Ankit V, Mahavir J, Hardik L and Praful B (2012). Nanosuspension technology. Int J Univ Pharm Life Sci 2(2): 306-17.
Bhowmik D, Harish G, Duraivel S and Kumar BP (2012). Nanosuspension-A novel approach in drug delivery system. J Pharma Innov 1(12): 50-63.
Chan VSW (2006). Nanomedicine: an unresolved regulatory issue. Regulatory Toxicology and Pharmacology 46: 3218-224.
Chen H, Wan J, Wang Y, Mou D, Liu H, Xu H, and Yang XA (2008). Facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid–base neutralization reactions. Nanotechnology 19: 375-378.
Chen X, Yong TJ, Sarkari M, Williams RO III and Johnston KP (2002). Preparation of cyclosporine nanoparticles by evaporative precipitation into aqueous solution. Int J Pharm 242: 3-14.
Cheng X, Li X and Wang Y. (2010). Taxol nanosuspension and preparation method thereof. CN201010174294.
Chiang PC, Alsup JW, Lai Y, Hu Y, Heyde BR, and Tung D (2009). Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery. Nanoscale Res Lett 4: 254-261.
Chingunpituk J. (2007). Nanosuspension technology for drug delivery. Walailak Journal of Science & Technology 4(2): 139-153.
Detroja C, Chavhan S, and Sawant K (2011). Enhanced antihypertensive activity of candesartan cilexetil nanosuspension formulation characterization and pharmacodynamic study. Sci Pharm 79: 635-651.
Dohrn R, Bertakis E, Behrend O, Voutsas E and Tassios D (2007). Melting point depression by using supercritical CO2 for a novel melt dipersion micronization process. J Mole Liq 131-132: 53-9.
Dolenc A, Kristl J, Baumgartner S, and Planinsek O (2009). Advantages of celecoxib nanosuspension formulation and transformation into tablets. Int J Pharm 376: 204-212.
Dong LC, Wong PSL and Zhao R. (2004). Formulation and dosage form providing increased bioavailability of hydrophobic drugs. US20040142040A1.
Eerdenbrugh BV, Froyen L, Humbeeck JV, Martens JA, Augustijns P and Mooter GVD (2008). Alternative matrix formers for nanosuspension solidification Dissolution performance and X-ray microanalysis as an evaluation tool for powder dispersion. Eur J Pharm Sci 35: 344-353.
Freitas RA. (2005). What is nanomedicine? Nanomedicine 1(1): 2–9.
Gao L, Liu G, Wang X, Liu F, Xu Y and Ma J (2011). Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm 404: 231-237.
Gao Y, Li Z, Sun M, Guo C, Yu A, Xi Y, Cui J, Lou H and Zhai G (2011). Preparation and characterization of intravenously injectable curcumin nanosuspension. Drug Deliv 18: 131-142.
Gao YA, Qian SA and Zhang JJ (2010). Physicochemical and Pharmacokinetic Characterization of a Spray-Dried Cefpodoxime Proxetil Nanosuspension. Chem Pharm Bull 58: 912-917.
Ghosh I, Bose S, Vippagunta R and Harmon F (2011). Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int J Pharm 409: 260-268.
Hanafy A, Spahn-Langguth H, Vergnault G, Grenier P, Grozdanis MT and Lenhardt T (2007). Pharmacokinetic evaluation of oral fenofibrate nanosuspension and SLN in comparison to conventional suspensions of micronized drug. Adv Drug Deliv Rev 59: 419-26.
Hao LL, Wang XY, Zhang DR, Xu QY, Song SY, Wang FH, Li CY, Guo HJ, Liu Y, Zheng DD and Zhang Q (2012). Studies on the preparation, characterization and pharmacokinetics of Amoitone B nanocrystals. Int J Pharm 433: 157-164.
Homar M, Cegnar M, Lovse BE, Peternel L and Kerc J. (2011). An aqueous intravenous nanosuspension with reduced adverse effects. WO2011080148.
Horn D and Rieger J (2001). Organic nanoparticles in the aqueous phase—theory experiment and use. Angew Chem Int Ed Engl 40: 4330-4361.
Ibrahim HM, Ismail Lila HR and AEA (2012). Formulation and optimization of ocular poly-D, L-lactic acid nano drug delivery system of amphotericin-B using box behnken design. International Journal of Pharmacy and Pharmaceutical Sciences 4(2): 342–349.
Itoh K, Pongpeerapat A, Tozuka Y, Oguchi T and Yamamoto K (2003). Nanoparticle formation of poorly water soluble drugs from ternary ground mixtures with PVP and SDS. Chem Pharm Bull 51: 171-4.
Jacobs C, Kayser O and Muller RH (2001). Production and characterization of mucoadhesive nanosuspensions for the formulation of bupravaquone. Int J Pharm 214: 3-7.
Kayser O, Olbrich C, Yardley V, Kiderlen AF and Croft SL (2003). Formulation of amphotericin B as nanosuspension for oral administration. Int J Pharm 254: 73-5.
Kocbek P, Baumgartner S and Kristl J (2006). Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drug. Int J Pharm 312: 179-86.
Kohno S, Otsubo T, Tanaka E, Maruyama K and Hara K (1997). Amphotericin B encapsulated in polyethylene glycol immunoliposomes for infectious diseases. Adv Drug Dev Rev 24: 325-9.
Kondo M, Niwa T, Okamoto H, and Danjo K (2009). Particle characterization of poorly water-soluble drugs using a spray freeze drying technique. Chem Pharm Bull (Tokyo) 57: 657-662.
Kumar BS and Sabera K (2013). Increasing possibilities of nanosuspension. Hindawi Pub Corp J Nanotech 2: 1-13.
Kumar MP, Rao YM and Apte S (2007). Improved bioavailability of albendazole following oral administration of nanosuspension in rats. Curr Nanosci 3: 191-4.
Kumar N, Deecarman C and Mohanraj K (2009). Preparation and solid state characterization of atorvastatin nanosuspension for enhanced solubility and dissolution. International Journal of PharmTech Research 1725-1730.
Langguth P, Hanafy A, Frenzel D, Grenier P, Nhamias A and Ohlig T (2005). Nanosuspension formulations for low-soluble drugs: Pharmacokinetic evaluation using spironolactone as model compound. Drug Dev Ind Pharm 31: 319-29.
Liu F, Park JY, Zhang Y, Conwell C, Liu Y, Bathula SR and Huang L (2010). Targeted Cancer Therapy with Novel High Drug-Loading Nanocrystals. J Pharm Sci 99: 3542-3551.
Liversidge GG and Conzentino P (1995). Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats. Int J Pharm 125: 309-13.
Merisko-Liversidge E, Liversidge GG and Cooper ER (2003). Nanosizing: A formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci 18: 113-20.
Morrow KJ, Bawa R and Wei C (2007). Recent advances in basic and clinical nanomedicine. Medical Clinics of North America 91(5): 805–843.
Moschwitzer J, Achleitner G, Pomper H and Muller RH (2004). Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology. Eur J Pharm Biopharm 58: 615-619.
Muller RH, Becker R, Kruss B and Peters K (2004). Process for the preparation of pharmaceutical nanosuspensions. EP0790821.
Muller RH, Becker R, Kruss B and Peters K. (1996). Pharmaceutical nanosuspensions for medicament administration as systems with increased saturation solubility and speed of dissolution.WO1996014830.
Muller RH, Becker R, Kruss B and Peters K. (1999). Pharmaceutical nanosuspensions for medicament administration as systems with increased saturation solubility and rate of solution. US5858410
Muller RH and Jacobs C (2002). Buparvaquone mucoadhesive nanosuspension: Preparation, optimisation and longterm stability. Int J Pharm 237: 151-61.
Muller RH and Jacobs C (2002). Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharm Res 19: 189-94.
Müller RH, Jacobs C and Kayser O (2001). Nanosuspension as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Advanced Drug Delivery Reviews 47: 3-19.
Muller RH, Jacobs C, Kayser O, Rathbone MJ, Hadgraft J and Roberts MS (2003). Modified release drug delivery technology. New York Basel 135-49.
Mura P, Cirri M, Faucci MT, Gines-Dorado JM and Bettinetti GP (2002). Investigation of the effects of grinding and co-grinding on physicochemical properties of glisentide. J Pharm Biomed Anal 30: 227-37.
Mura P, Faucci MT and Bettinetti GP (2001). The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl- cyclodextrin. Eur J Pharm Sci 13: 187-94.
Nakach M (2012). High-pressure homogenization with a silicon nitride valve: US20120127823
Nakamoto K, Urasaki T, Hondo S, Murahashi N, Yonemochi E and Terada K (2013). Evaluation of the crystalline and amorphous states of drug products by nanothermal analysis and Raman imaging. J Pharmaceut Biomed 75: 105-111.
Otsuka M and Matsuda Y (1995). Effect of co-grinding with various kinds of surfactants on the dissolution behavior of phenytoin. J Pharm Sci 84: 1434-7.
Patravale VB, Date AA and Kulkarni RM (2004). Nanosuspensions a promising drug delivery strategy. J Pharm Pharmacol 56: 827-840.
Peters K, Leitzke S, Diederichs JE, Borner K and Hahn H (2000). Preparation of a clofazamine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine mycobacterium avium infection. J Antimicrob Chemother 45: 77-83.
Pintu KD and Subrata C (2012). Nanosuspensions: Potent vehicles for drug delivery and bioavailability enhancement of lipophilic drugs. J Pharm Res 5(3): 1548-54.
Prabhakar C and Krishna KB (2011). A review on nanosuspensions in drug delivery. International Journal of Pharma and Bio Sciences 2(1): 549-558.
Praveen K and Kotty GK (2011). Nanosuspensions: The solution to deliver hydrophobic drugs. Int J Drug Deliv 3: 546-57.
Puri V, Dantuluri AK, Kumar M, Karar N and Bansal AK (2010). Wettability and surface chemistry of crystalline and amorphous forms of a poorly water soluble drug. Eur J Pharm Sci 40: 84-93.
Rabinow BE (2004). Nanosuspensions in drug delivery. Nature Reviews Drug Discovery 3(9): 785-796.
Rabinow B, Kipp J, Papadopoulos P, Wong J, Glosson J and Gass J (2007). Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int J Pharm 339: 251-60.
Ramsden J. (2011). What is nanotechnology? In Nanotechnology: An Introduction, Elsevier, New York, NY, USA, pp. 1–14.
Reddy GA and Anilchowdary Y (2012). Nanosuspension technology: A review. J Pharmaceut Cosmet 2(8): 47-52.
Sahoo SK, Parveen S, and Panda JJ (2007). The present and future of nanotechnology in human health care. Nanomedicine 3(1): 20-31.
Sarkari M, Brown J, Chen X, Swinnea S, Williams RO III and Johnston KP (2002). Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm 243: 17-31.
Scholer N, Krause K, Kayser O, Müller RH, Borner K and Hahn H (2001). Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother 45: 1719.
Sudhir V and Diane B (2010). Solid nanosuspensions: The emerging technology and pharmaceutical applications as nanomedicine. Springer AAPS Press, 285-318.
Sugimoto M, Okagaki T, Narisawa S, Koida Y and Nakajima K (1998). Improvement of dissolution characteristics and bioavailability of poorly water-soluble drugs by novel co-grinding method using water soluble polymer. Int J Pharm 160: 9-11.
Trotta M, Gallarate M, Carlotti ME and Morel S (2003). Preparation of griseofulvin nanoparticles from water-dilutable micro-emulsions. Int J Pharm 254: 235-42.
Trotta M, Gallarete M, Pattarino F and Morel S (2001). Emulsions containing partially water-miscible solvents for the preparation of dry nanosuspensions. J Control Rel. 76: 119-28.
Van EB, Van den MG and Augustijns P. (2008). Top-down production of drug nanocrystals: Nanosuspension stabilization, miniturization and transformation into solid products. Int J Pharma. 364: 64-75.
Wang SL, Jiang TY, Sun CS and Ma Q. (2013). Valsartan spray dried nanosuspension and preparation method of valsartan spray-dried nanosuspension. CN102920654A.
Wang YL, Li XM, Wang LY, Xu YL, Cheng XD and Wei P (2011). Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery. Int J Nanomedicine 6: 1497-1507.
Watanabe T, Ohno I, Wakiyama N, Kusai A and Senna M (2002). Stabilization of amorphous indomethacin by co-grinding in a ternary mixture. Int J Pharm 241: 103-11.
Wong DH, Kim MS, Lee S, Jeong SP and Hwang SJ (2005). Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process. Int J Pharm 301: 199-208.
Xiaohai T, Yu Q and Lilin P. (2011). Lyophilized formulation of pectin adriamycin conjugate and preparation method thereof. WO2011134368A1.
Yonemochi E, Kitahara S, Maeda S, Yamamura S, Oguchi T and Yamamoto K (1999). Physicochemical properties of amorphous clarithromycin obtained by grinding and spray drying. Eur J Pharm Sci 7: 331-8.
Zhang D, Tan T, Gao L, Zhao W and Wang P (2007). Preparation of azithromycin nanosuspensions by high pressure homogenization and its physicochemical characteristics studies. Drug Dev Ind Pharm 33: 569-77.
Zhang X and Xia Q (2006). Preparation of all-trans retinoic acid nanosuspensions using a modified precipitation method. Drug Dev Ind Pharm 32: 857-63.
