Abstract
Drug synthesis, high-throughput screening generates billions of poorly soluble drugs which are neglected in further developments due to solubility issues. In the last 20 years, nanonization by milling is being effectively used commercially to save these drugs by overcoming solubility problems in commercial way. Various labs at industry and academic level successfully investigated milling technique alone and in combination with other techniques to reduce particle size, thereby increasing the dissolution velocity of drug. Milling offers ease of production, efficient control of production parameters, freedom of small to industrial batch size, liberty to produce highly concentrated suspensions, and improved stability of final product. Nanonized slurries exhibited promising results in vitro and in vivo and many fold increase in bioavailability. Nanosuspensions are investigated for organ or cellular delivery in various diseases like HIV/AIDS, malaria, and other infectious disease conditions. The issue of metal abrasion and contamination is now nullified by effective engineering solutions. In this chapter, recent updates on milling techniques and their applications in pharmaceutical field are discussed.
This is a preview of subscription content, log in via an institution.
References
T. Niwa, Y. Nakanishi, K. Danjo, One-step preparation of pharmaceutical nanocrystals using ultra cryo-milling technique in liquid nitrogen. Eur. J. Pharm. Sci. 41, 78–85 (2010)
S. Sugimoto, T. Niwa, Y. Nakanishi, K. Danjo, Novel ultra-cryo milling and co-grinding technique in liquid nitrogen to produce dissolution-enhanced nanoparticles for poorly water-soluble drugs. Chem. Pharm. Bull. 60, 325–333 (2012)
S. Sugimoto, T. NIWA, Y. Nakanishi, K. Danjo, Development of a novel ultra cryo-milling technique for a poorly water-soluble drug using dry ice beads and liquid nitrogen. Int. J. Pharm. 426, 162–169 (2012)
G. Liversidge. Milling methods – nanoCrystalsTM. IIR drug delivery partnershipsTM meeting, workshop “Nanotechnology – solid particles, lipids and nanocomplexes”. Cologne (2003)
L. Peltonen, J. Hirvonen, Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods. J. Pharm. Pharmacol. 62, 1569–1579 (2010)
R. Shegokar, R.H. Müller, Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int. J. Pharm. 399, 129–139 (2010)
J. Salazar, R.H. Müller, J.P. Möschwitzer. Application of the combinative particle size reduction technology H 42 to produce fast dissolving glibenclamide tablets. Eur. J. Pharm. Sci. 49(4), 565–577 (2013). doi: 10.1016/j.ejps.2013.04.003. Epub 2013 Apr 12.
J.P. Moschwitzer. Drug nanocrystals in the commercial pharmaceutical development process. Int. J. Pharm. 453(1):142–156 (2012)
M. Kakran, N.G. Sahoo, L. Li, Z. Judeh, Dissolution of artemisinin/polymer composite nanoparticles fabricated by evaporative precipitation of nanosuspension. J. Pharm. Pharmacol. 62, 413–421 (2010)
Y. Wang, L. Wang, Z. Liu, D. Zhang, Q. Zhang, In vivo evaluation of silybin nanosuspensions targeting liver. J. Biomed. Nanotechnol. 8, 760–769 (2012)
Y. Wang, D. Zhang, Z. Liu, G. Liu, C. Duan, L. Jia, F. Feng, X. Zhang, Y. Shi, Q. Zhang, In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery. Nanotechnology 21, 155104 (2010)
L. Wang, M. Li, N. Zhang, Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy. Int. J. Nanomedicine 7, 3281–3294 (2012)
S.E. Lee, S.F. Bairstow, J.O. Werling, M.V. Chaubal, L. Lin, M.A. Murphy, J.P. Diorio, J. Gass, B. Rabinow, X. Wang, Y. Zhang, Z. Yang, R.M. Hoffman. Paclitaxel nanosuspensions for targeted chemotherapy – nanosuspension preparation, characterization, and use. Pharm. Dev. Technol. (2013)
B. van Eerdenbrugh, L. Froyen, J.A. Martens, N. Blaton, P. Augustijns, M. Brewster, G. van den Mooter, Characterization of physico-chemical properties and pharmaceutical performance of sucrose co-freeze-dried solid nanoparticulate powders of the anti-HIV agent loviride prepared by media milling. Int. J. Pharm. 338, 198–206 (2007)
B. van Eerdenbrugh, B. Stuyven, L. Froyen, J. van Humbeeck, J.A. Martens, P. Augustijns, G. van den Mooter, Downscaling drug nanosuspension production: processing aspects and physicochemical characterization. AAPS PharmSciTech 10, 44–53 (2009)
G. Van’t Klooster, R. Verloes, L. Baert, F. Van Velsen, M.P. Bouche, K. Spittaels, J. Leempoels, P. Williams, G. Kraus, P. Wigerinck. Long-acting TMC278, a parenteral depot formulation delivering therapeutic NNRTI concentrations in preclinical and clinical settings, in Conference Retrovir Opportunistic Infect, 3–6 Feb 2015 (Abstract no. 134) (2008)
M.G. Fakes, B.J. Vakkalagadda, F. Qian, S. Desikan, R.B. Gandhi, C. Lai, A. Hsieh, M.K. Franchini, H. Toale, J. Brown, Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing and amorphous formulation approaches. Int. J. Pharm. 370, 167–174 (2009)
S. Gahoi, G.K. Jain, R. Tripathi, S.K. Pandey, M. Anwar, M.H. Warsi, M. Singhal, R.K. Khar, F.J. Ahmad, Enhanced antimalarial activity of lumefantrine nanopowder prepared by wet-milling DYNO MILL technique. Colloids Surf. B Biointerfaces 95, 16–22 (2012)
J. Chingunpitak, S. Puttipipatkhachorn, P. Chavalitshewinkoon-Petmitr, Y. Tozuka, K. Moribe, K. Yamamoto, Formation, physical stability and in vitro antimalarial activity of dihydroartemisinin nanosuspensions obtained by co-grinding method. Drug Dev. Ind. Pharm. 34, 314–322 (2008)
K. Peters, S. Leitzke, J.E. Diederichs, K. Borner, H. Hahn, R.H. Müller, S. Ehlers, Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. J. Antimicrob. Chemother. 45, 77–83 (2000)
O. Kayser, A.F. Kiderlen, S. Bertels, K. Siems, Antileishmanial activities of aphidicolin and its semisynthetic derivatives. Antimicrob. Agents Chemother. 45, 288–292 (2001)
O. Kayser, Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against leishmania infected macrophages. Int. J. Pharm. 196, 253–256 (2000)
N. Schöler, K. Krause, O. Kayser, R.H. Müller, K. Borner, H. Hahn, O. Liesenfeld, Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob. Agents Chemother. 45, 1771–1779 (2001)
Y. Chen, J. Liu, X. Yang, X. Zhao, H. Xu, Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect. J. Pharm. Pharmacol. 57, 259–264 (2005)
S. Latha, P. Selvamani, C.S. Kumar, P. Sharavanan, G. Suganya, V.S. Beniwal, P.R. Rao, Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system. J. Magn. Magn. Mater. 321, 1580–1585 (2009)
Z. Zhang, X. Zhang, W. Xue, Y. Yangyang, D. Xu, Y. Zhao, H. Lou, Effects of oridonin nanosuspension on cell proliferation and apoptosis of human prostatic carcinoma PC-3 cell line. Int. J. Nanomedicine 5, 735–742 (2010)
H. Lou, X. Zhang, L. Gao, F. Feng, J. Wang, X. Wei, Z. Yu, D. Zhang, Q. Zhang, In vitro and in vivo antitumor activity of oridonin nanosuspension. Int. J. Pharm. 379, 181–186 (2009)
H. Zhang, C.P. Hollis, Q. Zhang, T. Li, Preparation and antitumor study of camptothecin nanocrystals. Int. J. Pharm. 415, 293–300 (2011)
P.C. Chiang, Y. Ran, K.J. Chou, Y. Cui, H. Wong, Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3-dicyclohexylurea in rats: preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery. Nanoscale Res. Lett. 6, 413 (2011)
K. Mitri, R. Shegokar, S. Gohla, C. Anselmi, R.H. Muller, Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int. J. Pharm. 420, 141–146 (2011)
L. Al Shaal, R.H. Müller, R. Shegokar, smartCrystal combination technology–scale up from lab to pilot scale and long term stability. Pharmazie 65, 877–84 (2010)
J. Pardeike, R.H. Muller, Dermal and ocular safety of the new phospholipase A2 inhibitors PX-18 and PX-13 formulated as drug nanosuspension. J. Biomed. Nanotechnol. 5, 437–444 (2009)
R. Shegokar, K.K. Singh, Surface modified nevirapine nanosuspensions for viral reservoir targeting: In vitro and in vivo evaluation. Int. J. Pharm. 421, 341–352 (2011)
R.H. Müller, C. Jacobs, Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. Int. J. Pharm. 237, 151–161 (2002)
H.M. Shubar, S. Lachenmaier, M.M. Heimesaat, U. Lohman, R. Mauludin, R.H. Mueller, R. Fitzner, K. Borner, O. Liesenfeld, SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers. J. Drug Target. 19, 114–124 (2011)
A. Lemke, A.F. Kiderlen, B. Petri, O. Kayser, Delivery of amphotericin B nanosuspensions to the brain and determination of activity against Balamuthia mandrillaris amebas. Nanomed. Nanotechnol. Biol. Med. 6, 597–603 (2010)
R. Xiong, W. Lu, P. Yue, R. Xu, J. Li, T. Chen, P. Wang, Distribution of an intravenous injectable nimodipine nanosuspension in mice. J. Pharm. Pharmacol. 60, 1155–1159 (2008)
L. AL Shaal, R. Shegokar, R.H. Müller. Layer-by-Layer (LBL) coated antioxidant nanocrystals for oral delivery. (American Association of Pharmaceutical Scientists (AAPS), Washington, DC, 2011), 23–27th Oct 2011, PO:T3152
E. Merisko-Liversidge, G.G. Liversidge, E.R. Cooper, Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur. J. Pharm. Sci. 18, 113–120 (2003)
R. Shegokar, M. Jansch, K.K. Singh, R.H. Muller, In vitro protein adsorption studies on nevirapine nanosuspensions for HIV/AIDS chemotherapy. Nanomed. Nanotechnol. Biol. Med. 7, 333–340 (2011)
R. Shegokar, K.K. Singh, R.H. Müller, Nevirapine nanosuspension: comparative investigation of production methods. Nanotechnol. Dev 1(1), 16–22 (2011)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this entry
Cite this entry
Shegokar, R. (2015). Wet Media Milling: An Effective Way to Solve Drug Solubility Issue. In: Aliofkhazraei, M. (eds) Handbook of Nanoparticles. Springer, Cham. https://doi.org/10.1007/978-3-319-13188-7_20-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-13188-7_20-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Online ISBN: 978-3-319-13188-7
eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics