Nanomilling of drugs for bioavailability enhancement: A holistic formulation-process perspective

Pharmaceutics

Volumn 8, Issue 2, 2016, Pages

  Li, Meng ^a   Azad, Mohammad ^a   Davé, Rajesh ^a   Bilgili, Ecevit ^a  

^a NEW JERSEY INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Drug nanoparticles; Process modeling; Process parameters; Stabilization; Wet stirred media milling

Indexed keywords

ANIONIC SURFACTANT; DISINTEGRATING AGENT; NANOPARTICLE; NONIONIC SURFACTANT; POLYMER;

CONTAMINATION; DRUG BIOAVAILABILITY; DRUG CONCENTRATION; DRUG FORMULATION; DRUG SYNTHESIS; HYDRODYNAMICS; MATHEMATICAL MODEL; MECHANICAL STRESS; NANOMILLING; NANOPHARMACEUTICS; PARTICLE SIZE; PHYSICAL CHEMISTRY; REVIEW; SOLID STATE; SUSPENSION;

EID: 84973295204     PISSN: None     EISSN: 19994923     Source Type: Journal    
DOI: 10.3390/pharmaceutics8020017     Document Type: Review

References (188)

1. Kipp, J.E. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int. J. Pharm. 2004, 284, 109-122. [CrossRef] [PubMed]
2. Lipinski, C.A. Poor aqueous solubility: An industry wide problem in drug discovery. Am. Pharm. Rev. 2002, 5, 82-85.
3. Chawla, G.; Bansal, A.K. A comparative assessment of solubility advantage from glassy and crystalline forms of a water-insoluble drug. Eur. J. Pharm. Sci. 2007, 32, 45-57. [CrossRef] [PubMed]
4. Shah, B.; Kakumanu, V.K.; Bansal, A.K. Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J. Pharm. Sci. 2006, 95, 1641-1665. [CrossRef] [PubMed]
5. Singh, S.K.; Srinivasan, K.; Gowthamarajan, K.; Singare, D.S.; Prakash, D.; Gaikwad, N.B. 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, 441-446. [CrossRef] [PubMed]
6. Tanaka, Y.; Inkyo, M.; Yumoto, R.; Nagai, J.; Takano, M.; Nagata, S. Nanoparticulation of probucol, a poorly water-soluble drug, using a novel wet-milling process to improve in vitro dissolution and in vivo oral absorption. Drug Dev. Ind. Pharm. 2012, 38, 1015-1023. [CrossRef] [PubMed]
7. Tuomela, A.; Liu, P.; Puranen, J.; Rönkkö, S.; Laaksonen, T.; Kalesnykas, G.; Oksala, O.; Ilkka, J.; Laru, J.; Järvinen, K. et al. Brinzolamide nanocrystal formulations for ophthalmic delivery: Reduction of elevated intraocular pressure in vivo. Int. J. Pharm. 2014, 467, 34-41. [CrossRef] [PubMed]
8. Noyes, A.A.; Whitney, W.R. The rate of solution of solid substances in their own solutions. J. Am. Chem. Soc. 1897, 19, 930-934. [CrossRef]
9. Müller, R.H.; Böhm, B.H. Nanosuspensions. In Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs; Benita, S., Böhm, B.H., Eds.; Medpharm Scientific: Stuttgart, Germany, 1998; pp. 149-173.
10. Möschwitzer, J.; Müller, R.H.; Hunter, R.; Preedy, V. Nanocrystal formulations for improved delivery of poorly soluble drugs. In Nanomedicine in Health and Disease; Hunter, R.J., Preedy, V.R., Eds.; CRC Press: New York, NY, USA, 2011; pp. 79-99.
11. Kumar, P.; Krishna, K.G. Nanosuspensions: The solution to deliver hydrophobic drugs. Int. J. Drug Deliv. 2012, 3, 546-557.
12. Patravale, V.; Kulkarni, R. Nanosuspensions: A promising drug delivery strategy. J. Pharm. Pharmacol. 2004, 56, 827-840. [CrossRef] [PubMed]
13. Rao, B.S.; Dubey, S.S. Nano fabricated drug delivery devises. Int. J. Pharm. Technol. 2012, 4, 1974-1986.
14. Sun, B.; Yeo, Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr. Opin. Solid State Mater. Sci. 2012, 16, 295-301. [CrossRef] [PubMed]
15. Wacker, M. Nanocarriers for intravenous injection-The long hard road to the market. Int. J. Pharm. 2013, 457, 50-62. [CrossRef] [PubMed]
16. Zhang, J.; Wu, L.; Chan, H.-K.; Watanabe, W. Formation, characterization, and fate of inhaled drug nanoparticles. Adv. Drug Deliv. Rev. 2011, 63, 441-455. [CrossRef] [PubMed]
17. Chingunpituk, J. Nanosuspension technology for drug delivery. Walailak J. Sci. Technol. 2011, 4, 139-153.
18. Date, A.A.; Patravale, V. Current strategies for engineering drug nanoparticles. Curr. Opin. Colloid Interface Sci. 2004, 9, 222-235. [CrossRef]
19. Leleux, J.; Williams, R.O. Recent advancements in mechanical reduction methods: Particulate systems. Drug Dev. Ind. Pharm. 2014, 40, 289-300. [CrossRef] [PubMed]
20. Paradkar, A.; Ambike, A.A.; Jadhav, B.K.; Mahadik, K.R. Characterization of curcumin-PVP solid dispersion obtained by spray drying. Int. J. Pharm. 2004, 271, 281-286. [CrossRef] [PubMed]
21. Kesisoglou, F.; Panmai, S.; Wu, Y. Application of nanoparticles in oral delivery of immediate release formulations. Curr. Nanosci. 2007, 3, 183-190. [CrossRef]
22. Merisko-Liversidge, E.M.; Liversidge, G.G. Drug nanoparticles: Formulating poorly water-soluble compounds. Toxicol. Pathol. 2008, 36, 43-48. [CrossRef] [PubMed]
23. Van Eerdenbrugh, B.; Froyen, L.; van Humbeeck, J.; Martens, J.A.; Augustijns, P.; van den Mooter, G. Drying of crystalline drug nanosuspensions-The importance of surface hydrophobicity on dissolution behavior upon redispersion. Eur. J. Pharm. Sci. 2008, 35, 127-135. [CrossRef] [PubMed]
24. Müller, R.H.; Jacobs, C.; Kayser, O. Nanosuspensions as particulate drug formulations in therapy: Rationale for development and what we can expect for the future. Adv. Drug Deliv. Rev. 2001, 47, 3-19. [CrossRef]
25. Müller, R.H.; Peters, K. Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. Int. J. Pharm. 1998, 160, 229-237. [CrossRef]
26. Rabinow, B.E. Nanosuspensions in drug delivery. Nat. Rev. Drug Discov. 2004, 3, 785-796. [CrossRef] [PubMed]
27. Cooper, E.R. Nanoparticles: A personal experience for formulating poorly water soluble drugs. J. Control. Release 2010, 141, 300-302. [CrossRef] [PubMed]
28. Basa, S.; Muniyappan, T.; Karatgi, P.; Prabhu, R.; Pillai, R. Production and in vitro characterization of solid dosage form incorporating drug nanoparticles. Drug Dev. Ind. Pharm. 2008, 34, 1209-1218. [CrossRef] [PubMed]
29. Bhakay, A.; Azad, M.; Vizzotti, E.; Dave, R.N.; Bilgili, E. Enhanced recovery and dissolution of griseofulvin nanoparticles from surfactant-free nanocomposite microparticles incorporating wet-milled swellable dispersants. Drug Dev. Ind. Pharm. 2014, 40, 1509-1522. [CrossRef] [PubMed]
30. Lee, J. Drug nano-and microparticles processed into solid dosage forms: Physical properties. J. Pharm. Sci. 2003, 92, 2057-2068. [CrossRef] [PubMed]
31. Van Eerdenbrugh, B.; van den Mooter, G.; Augustijns, P. Top-down production of drug nanocrystals: Nanosuspension stabilization, miniaturization and transformation into solid products. Int. J. Pharm. 2008, 364, 64-75. [CrossRef] [PubMed]
32. Knieke, C.; Azad, M.A.; To, D.; Bilgili, E.; Davé, R.N. Sub-100 micron fast dissolving nanocomposite drug powders. Powder Technol. 2015, 271, 49-60. [CrossRef]
33. Tuomela, A.; Laaksonen, T.; Laru, J.; Antikainen, O.; Kiesvaara, J.; Ilkka, J.; Oksala, O.; Rönkkö, S.; Järvinen, K.; Hirvonen, J. et al. Solid formulations by a nanocrystal approach: Critical process parameters regarding scale-ability of nanocrystals for tableting applications. Int. J. Pharm. 2015, 485, 77-86. [CrossRef] [PubMed]
34. Patel, M.; Munjal, B.; Bansal, A.K. Differential effect of buffering agents on the crystallization of gemcitabine hydrochloride in frozen solutions. Int. J. Pharm. 2014, 471, 56-64. [CrossRef] [PubMed]
35. Azad, M.; Arteaga, C.; Abdelmalek, B.; Davé, R.; Bilgili, E. Spray drying of drug-swellable dispersant suspensions for preparation of fast-dissolving, high drug-loaded, surfactant-free nanocomposites. Drug Dev. Ind. Pharm. 2015, 1617-1631. [CrossRef] [PubMed]
36. Sievens-Figueroa, L.; Bhakay, A.; Jerez-Rozo, J.I.; Pandya, N.; Romañach, R.J.; Michniak-Kohn, B.; Iqbal, Z.; Bilgili, E.; Davé, R.N. Preparation and characterization of hydroxypropyl methyl cellulose films containing stable BCS Class II drug nanoparticles for pharmaceutical applications. Int. J. Pharm. 2012, 423, 496-508. [CrossRef] [PubMed]
37. Krull, S.M.; Susarla, R.; Afolabi, A.; Li, M.; Ying, Y.; Iqbal, Z.; Bilgili, E.; Davé, R.N. Polymer strip films as a robust, surfactant-free platform for delivery of BCS Class II drug nanoparticles. Int. J. Pharm. 2015, 489, 45-57. [CrossRef] [PubMed]
38. Susarla, R.; Afolabi, A.; Patel, D.; Bilgili, E.; Davé, R.N. Novel use of superdisintegrants as viscosity enhancing agents in biocompatible polymer films containing griseofulvin nanoparticles. Powder Technol. 2015, 285, 25-33. [CrossRef]
39. Bhakay, A.; Vizzotti, E.; Li, M.; Davé, R.; Bilgili, E. Incorporation of fenofibrate nanoparticles prepared by melt emulsification into polymeric films. J. Pharm. Innov. 2016, 11, 53-63. [CrossRef]
40. Krull, S.M.; Ma, Z.; Li, M.; Davé, R.N.; Bilgili, E. Preparation and characterization of fast dissolving pullulan films containing BCS Class II drug nanoparticles for bioavailability enhancement. Drug Dev. Ind. Pharm. 2016, 42, 1073-1085. [CrossRef] [PubMed]
41. Kwade, A. Wet comminution in stirred media mills-Research and its practical application. Powder Technol. 1999, 105, 14-20. [CrossRef]
42. Merisko-Liversidge, E.; Liversidge, G.G.; Cooper, E.R. Nanosizing: A formulation approach for poorly-water-soluble compounds. Eur. J. Pharm. Sci. 2003, 18, 113-120. [CrossRef]
43. Brough, C.; Williams, R. Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int. J. Pharm. 2013, 453, 157-166. [CrossRef] [PubMed]
44. Möschwitzer, J.P. Drug nanocrystals in the commercial pharmaceutical development process. Int. J. Pharm. 2013, 453, 142-156. [CrossRef] [PubMed]
45. Afolabi, A.; Akinlabi, O.; Bilgili, E. Impact of process parameters on the breakage kinetics of poorly water-soluble drugs during wet stirred media milling: A microhydrodynamic view. Eur. J. Pharm. Sci. 2014, 51, 75-86. [CrossRef] [PubMed]
46. Cerdeira, A.M.; Gander, B.; Mazzotti, M. Role of milling parameters and particle stabilization on nanogrinding of drug substances of similar mechanical properties. Chem. Eng. Technol. 2011, 34, 1427-1438. [CrossRef]
47. Ghosh, I.; Schenck, D.; Bose, S.; Ruegger, C. Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: Effect of Vitamin E TPGs and nanocrystal particle size on oral absorption. Eur. J. Pharm. Sci. 2012, 47, 718-728. [CrossRef] [PubMed]
48. Merisko-Liversidge, E.; Liversidge, G.G. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv. Drug Deliv. Rev. 2011, 63, 427-440. [CrossRef] [PubMed]
49. Eskin, D.; Zhupanska, O.; Hamey, R.; Moudgil, B.; Scarlett, B. Microhydrodynamics of stirred media milling. Powder Technol. 2005, 156, 95-102. [CrossRef]
50. Bernotat, S.; Schönert, K. Size reduction. In Ullmann’s Encyclopedia of Industrial Chemistry; Springer: Berlin, Germany, 1988; pp. 199-905.
51. Kesisoglou, F.; Panmai, S.; Wu, Y. Nanosizing-Oral formulation development and biopharmaceutical evaluation. Adv. Drug Deliv. Rev. 2007, 59, 631-644. [CrossRef] [PubMed]
52. Shegokar, R.; Müller, R.H. Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives. Int. J. Pharm. 2010, 399, 129-139. [CrossRef] [PubMed]
53. Wu, L.; Zhang, J.; Watanabe, W. Physical and chemical stability of drug nanoparticles. Adv. Drug Deliv. Rev. 2011, 63, 456-469. [CrossRef] [PubMed]
54. Wang, Y.; Zheng, Y.; Zhang, L.; Wang, Q.; Zhang, D. Stability of nanosuspensions in drug delivery. J. Control. Release 2013, 172, 1126-1141. [CrossRef] [PubMed]
55. Junyaprasert, V. B.; Morakul, B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J. Pharm. Sci. 2015, 10, 13-23. [CrossRef]
56. Peltonen, L.; Hirvonen, J. Pharmaceutical nanocrystals by nanomilling: Critical process parameters, particle fracturing and stabilization methods. J. Pharm. Pharmacol. 2010, 62, 1569-1579. [CrossRef] [PubMed]
57. Cerdeira, A.M.; Mazzotti, M.; Gander, B. Miconazole nanosuspensions: Influence of formulation variables on particle size reduction and physical stability. Int. J. Pharm. 2010, 396, 210-218. [CrossRef] [PubMed]
58. Bhakay, A.; Davé, R.; Bilgili, E. Recovery of BCS Class II drugs during aqueous redispersion of core-shell type nanocomposite particles produced via fluidized bed coating. Powder Technol. 2013, 236, 221-234. [CrossRef]
59. Bitterlich, A.; Laabs, C.; Busmann, E.; Grandeury, A.; Juhnke, M.; Bunjes, H.; Kwade, A. Challenges in nanogrinding of active pharmaceutical ingredients. Chem. Eng. Technol. 2014, 37, 840-846. [CrossRef]
60. Colombo, I.; Grassi, G.; Grassi, M. Drug mechanochemical activation. J. Pharm. Sci. 2009, 98, 3961-3986. [CrossRef] [PubMed]
61. Li, M.; Yaragudi, N.; Afolabi, A.; Dave, R.; Bilgili, E. Sub-100 nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification. Chem. Eng. Sci. 2015, 130, 207-220. [CrossRef]
62. Chin, C. P.; Wu, H. S.; Wang, S.S. New approach to pesticide delivery using nanosuspensions: Research and applications. Ind. Eng. Chem. Res. 2011, 50, 7637-7643. [CrossRef]
63. Juhnke, M.; Berghausen, J.; Timpe, C. Accelerated formulation development for nanomilled active pharmaceutical ingredients using a screening approach. Chem. Eng. Technol. 2010, 33, 1412-1418. [CrossRef]
64. Knieke, C.; Azad, M.; Davé, R.; Bilgili, E. A study of the physical stability of wet media-milled fenofibrate suspensions using dynamic equilibrium curves. Chem. Eng. Res. Des. 2013, 91, 1245-1258. [CrossRef]
65. Bhakay, A.; Merwade, M.; Bilgili, E.; Dave, R.N. Novel aspects of wet milling for the production of microsuspensions and nanosuspensions of poorly water-soluble drugs. Drug Dev. Ind. Pharm. 2011, 37, 963-976. [CrossRef] [PubMed]
66. Opoczky, L.; Farnady, F. Fine grinding and states of equilibrium. Powder Technol. 1984, 39, 107-115. [CrossRef]
67. Leung, D.H.; Lamberto, D.J.; Liu, L.; Kwong, E.; Nelson, T.; Rhodes, T.; Bak, A. A new and improved method for the preparation of drug nanosuspension formulations using acoustic mixing technology. Int. J. Pharm. 2014, 473, 10-19. [CrossRef] [PubMed]
68. Li, M.; Zhang, L.; Davé, R.; Bilgili, E. An intensified vibratory milling process for enhancing the breakage kinetics during the preparation of drug nanosuspensions. AAPS PharmSciTech 2016, 17, 389-399. [CrossRef] [PubMed]
69. Bilgili, E.; Afolabi, A. A combined microhydrodynamics-polymer adsorption analysis for elucidation of the roles of stabilizers in wet stirred media milling. Int. J. Pharm. 2012, 439, 193-206. [CrossRef] [PubMed]
70. Bilgili, E.; Li, M.; Afolabi, A. Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions? Pharm. Dev. Technol. 2016, 21, 199-510. [CrossRef] [PubMed]
71. Verma, S.; Huey, B.D.; Burgess, D.J. Scanning probe microscopy method for nanosuspension stabilizer selection. Langmuir 2009, 25, 12481-12487. [CrossRef] [PubMed]
72. Goodwin, D.J.; Sepassi, S.; King, S.M.; Holland, S.J.; Martini, L.G.; Lawrence, M.J. Characterization of polymer adsorption onto drug nanoparticles using depletion measurements and small-angle neutron scattering. Mol. Pharm. 2013, 10, 4146-4158. [CrossRef] [PubMed]
73. Bitterlich, A.; Laabs, C.; Krautstrunk, I.; Dengler, M.; Juhnke, M.; Grandeury, A.; Bunjes, H.; Kwade, A. Process parameter dependent growth phenomena of naproxen nanosuspension manufactured by wet media milling. Eur. J. Pharm. Biopharm. 2015, 92, 171-179. [CrossRef] [PubMed]
74. Dong, D.; Wang, X.; Wang, H.; Zhang, X.; Wang, Y.; Wu, B. Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: A case study with the anticancer agent SNX-2112. Int. J. Nanomed. 2015, 10, 2521-2535.
75. Kumar, S.; Jog, R.; Shen, J.; Zolnik, B.; Sadrieh, N.; Burgess, D.J. Formulation and performance of danazol nano-crystalline suspensions and spray dried powders. Pharm. Res. 2015, 32, 1694-1703. [CrossRef] [PubMed]
76. Bhakay, A.; Azad, M.; Bilgili, E.; Dave, R. Redispersible fast dissolving nanocomposite microparticles of poorly water-soluble drugs. Int. J. Pharm. 2014, 461, 367-379. [CrossRef] [PubMed]
77. Komasaka, T.; Fujimura, H.; Tagawa, T.; Sugiyama, A.; Kitano, Y. Practical method for preparing nanosuspension formulations for toxicology studies in the discovery stage: Formulation optimization and in vitro/in vivo evaluation of nanosized poorly water-soluble compounds. Chem. Pharm. Bull. 2014, 62, 1073-1082. [CrossRef] [PubMed]
78. Leng, D.; Chen, H.; Li, G.; Guo, M.; Zhu, Z.; Xu, L.; Wang, Y. Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size. Int. J. Pharm. 2014, 472, 380-385. [CrossRef] [PubMed]
79. Mahesh, K.V.; Singh, S.K.; Gulati, M. A comparative study of top-down and bottom-up approaches for the preparation of nanosuspensions of glipizide. Powder Technol. 2014, 256, 436-449. [CrossRef]
80. Shah, S.R.; Parikh, R.H.; Chavda, J.R.; Sheth, N.R. Glibenclamide nanocrystals for bioavailability enhancement: Formulation design, process optimization, and pharmacodynamic evaluation. J. Pharm. Innov. 2014, 9, 227-237. [CrossRef]
81. Sarnes, A.; Kovalainen, M.; Häkkinen, M.R.; Laaksonen, T.; Laru, J.; Kiesvaara, J.; Ilkka, J.; Oksala, O.; Rönkkö, S.; Järvinen, K. et al. Nanocrystal-based per-oral itraconazole delivery: Superior in vitro dissolution enhancement vs. sporanox® is not realized in in vivo drug absorption. J. Control. Release 2014, 180, 109-116. [CrossRef] [PubMed]
82. Yuminoki, K.; Seko, F.; Horii, S.; Takeuchi, H.; Teramoto, K.; Nakada, Y.; Hashimoto, N. Preparation and evaluation of high dispersion stable nanocrystal formulation of poorly water-soluble compounds by using povacoat. J. Pharm. Sci. 2014, 103, 3772-3781. [CrossRef] [PubMed]
83. Cerdeira, A.M.; Mazzotti, M.; Gander, B. Formulation and drying of miconazole and itraconazole nanosuspensions. Int. J. Pharm. 2013, 443, 209-220. [CrossRef] [PubMed]
84. George, M.; Ghosh, I. Identifying the correlation between drug/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology. Eur. J. Pharm. Sci. 2013, 48, 142-152. [CrossRef] [PubMed]
85. Monteiro, A.; Afolabi, A.; Bilgili, E. Continuous production of drug nanoparticle suspensions via wet stirred media milling: A fresh look at the rehbinder effect. Drug Dev. Ind. Pharm. 2013, 39, 266-283. [CrossRef] [PubMed]
86. Niwa, T.; Danjo, K. Design of self-dispersible dry nanosuspension through wet milling and spray freeze-drying for poorly water-soluble drugs. Eur. J. Pharm. Sci. 2013, 50, 272-281. [CrossRef] [PubMed]
87. Ali, H.S.M.; York, P.; Ali, A.M.A.; Blagden, N. Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling. J. Control. Release 2011, 149, 175-181. [CrossRef] [PubMed]
88. Ghosh, I.; Bose, S.; Vippagunta, R.; Harmon, F. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int. J. Pharm. 2011, 409, 260-268. [CrossRef] [PubMed]
89. Liu, P.; Rong, X.; Laru, J.; van Veen, B.; Kiesvaara, J.; Hirvonen, J.; Laaksonen, T.; Peltonen, L. Nanosuspensions of poorly soluble drugs: Preparation and development by wet milling. Int. J. Pharm. 2011, 411, 215-222. [CrossRef] [PubMed]
90. Patel, D.J.; Patel, J.K.; Pandya, V.M. Improvement in the dissolution of poorly water soluble drug using media milling technique. Thai J. Pharm. Sci. 2010, 34, 155-164.
91. Baert, L.; van’t Klooster, G.; Dries, W.; François, M.; Wouters, A.; Basstanie, E.; Iterbeke, K.; Stappers, F.; Stevens, P.; Schueller, L. et al. Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment. Eur. J. Pharm. Biopharm. 2009, 72, 502-508. [CrossRef] [PubMed]
92. Fakes, M.G.; Vakkalagadda, B.J.; Qian, F.; Desikan, S.; Gandhi, R.B.; Lai, C.; Hsieh, A.; Franchini, M.K.; Toale, H.; Brown, J. Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing and amorphous formulation approaches. Int. J. Pharm. 2009, 370, 167-174. [CrossRef] [PubMed]
93. Tanaka, Y.; Inkyo, M.; Yumoto, R.; Nagai, J.; Takano, M.; Nagata, S. Nanoparticulation of poorly water soluble drugs using a wet-mill process and physicochemical properties of the nanopowders. Chem. Pharm. Bull. 2009, 57, 1050-1057. [CrossRef] [PubMed]
94. Van Eerdenbrugh, B.; Vermant, J.; Martens, J.A.; Froyen, L.; van Humbeeck, J.; Augustijns, P.; van den Mooter, G. A screening study of surface stabilization during the production of drug nanocrystals. J. Pharm. Sci. 2009, 98, 2091-2103. [CrossRef] [PubMed]
95. Ain-Ai, A.; Gupta, P.K. Effect of arginine hydrochloride and hydroxypropyl cellulose as stabilizers on the physical stability of high drug loading nanosuspensions of a poorly soluble compound. Int. J. Pharm. 2008, 351, 282-288. [CrossRef] [PubMed]
96. Choi, J.-Y.; Park, C.H.; Lee, J. Effect of polymer molecular weight on nanocomminution of poorly soluble drug. Drug Deliv. 2008, 15, 347-353. [CrossRef] [PubMed]
97. Deng, Z.; Xu, S.; Li, S. Understanding a relaxation behavior in a nanoparticle suspension for drug delivery applications. Int. J. Pharm. 2008, 351, 236-243. [CrossRef] [PubMed]
98. Lee, J.; Choi, J.Y.; Park, C.H. Characteristics of polymers enabling nano-comminution of water-insoluble drugs. Int. J. Pharm. 2008, 355, 328-336. [CrossRef] [PubMed]
99. Dai, W.-G.; Dong, L.C.; Song, Y.-Q. Nanosizing of a drug/carrageenan complex to increase solubility and dissolution rate. Int. J. Pharm. 2007, 342, 201-207. [CrossRef] [PubMed]
100. Sepassi, S.; Goodwin, D.J.; Drake, A.F.; Holland, S.; Leonard, G.; Martini, L.; Lawrence, M.J. Effect of polymer molecular weight on the production of drug nanoparticles. J. Pharm. Sci. 2007, 96, 2655-2666. [CrossRef] [PubMed]
101. Van Eerdenbrugh, B.; Froyen, L.; Martens, J.; Blaton, N.; Augustijns, P.; Brewster, M.; van den Mooter, G. 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. 2007, 338, 198-206. [CrossRef] [PubMed]
102. Jinno, J.-I.; Kamada, N.; Miyake, M.; Yamada, K.; Mukai, T.; Odomi, M.; Toguchi, H.; Liversidge, G.G.; Higaki, K.; Kimura, T. Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. J. Control. Release 2006, 111, 56-64. [CrossRef] [PubMed]
103. Choi, J.-Y.; Yoo, J.Y.; Kwak, H.-S.; Uk Nam, B.; Lee, J. Role of polymeric stabilizers for drug nanocrystal dispersions. Curr. Appl. Phys. 2005, 5, 472-474. [CrossRef]
104. Lee, M.K.; Kim, S.; Ahn, C.H.; Lee, J. Hydrophilic and hydrophobic amino acid copolymers for nano-comminution of poorly soluble drugs. Int. J. Pharm. 2010, 384, 173-180. [CrossRef] [PubMed]
105. Dalvi, S.V.; Dave, R.N. Analysis of nucleation kinetics of poorly water-soluble drugs in presence of ultrasound and hydroxypropyl methyl cellulose during antisolvent precipitation. Int. J. Pharm. 2010, 387, 172-179. [CrossRef] [PubMed]
106. Rasenack, N.; Hartenhauer, H.; Müller, B.W. Microcrystals for dissolution rate enhancement of poorly water-soluble drugs. Int. J. Pharm. 2003, 254, 137-145. [CrossRef]
107. Azad, M.; Afolabi, A.; Bhakay, A.; Leonardi, J.; Davé, R.; Bilgili, E. Enhanced physical stabilization of fenofibrate nanosuspensions via wet co-milling with a superdisintegrant and an adsorbing polymer. Eur. J. Pharm. Biopharm. 2015, 94, 372-385. [CrossRef] [PubMed]
108. Onoue, S.; Takahashi, H.; Kawabata, Y.; Seto, Y.; Hatanaka, J.; Timmermann, B.; Yamada, S. Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability. J. Pharm. Sci. 2010, 99, 1871-1881. [CrossRef] [PubMed]
109. Berglund, K.D.; Przybycien, T.M.; Tilton, R.D. Coadsorption of sodium dodecyl sulfate with hydrophobically modified nonionic cellulose polymers. 1. Role of polymer hydrophobic modification. Langmuir 2003, 19, 2705-2713. [CrossRef]
110. Evertsson, H.; Nilsson, S. Microviscosity in clusters of ethyl hydroxyethyl cellulose and sodium dodecyl sulfate formed in dilute aqueous solutions as determined with fluorescence probe techniques. Macromolecules 1997, 30, 2377-2385. [CrossRef]
111. Winnik, F.M.; Winnik, M.A. The interaction of sodium dodecylsulfate with (hydroxypropyl) cellulose. Polym. J. 1990, 22, 482-488. [CrossRef]
112. Shimabayashi, S.; Uno, T.; Oouchi, Y.; Komatsu, E. Interaction between hydroxypropylcellulose and surfactant and its effect on dispersion stability of kaolinite suspension in an aqueous phase. In Formation and Dynamics of Self-Organized Structures in Surfactants and Polymer Solutions; Springer: Berlin, Germany, 1997; pp. 136-140.
113. Verma, S.; Kumar, S.; Gokhale, R.; Burgess, D.J. Physical stability of nanosuspensions: Investigation of the role of stabilizers on ostwald ripening. Int. J. Pharm. 2011, 406, 145-152. [CrossRef] [PubMed]
114. Jeong, Y.-I.; Shim, Y.-H.; Kim, C.; Lim, G.-T.; Choi, K.-C.; Yoon, C. Effect of cryoprotectants on the reconstitution of surfactant-free nanoparticles of poly (DL-lactide-co-glycolide). J. Microencapsul. 2005, 22, 593-601. [CrossRef] [PubMed]
115. Lebhardt, T.; Roesler, S.; Uusitalo, H.P.; Kissel, T. Surfactant-free redispersible nanoparticles in fast-dissolving composite microcarriers for dry-powder inhalation. Eur. J. Pharm. Biopharm. 2011, 78, 90-96. [CrossRef] [PubMed]
116. Liversidge, G.G.; Cundy, K.C. 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, 91-97. [CrossRef]
117. Azad, M.A.; Afolabi, A.; Patel, N.; Davé, R.; Bilgili, E. Preparation of stable colloidal suspensions of superdisintegrants via wet stirred media milling. Particuology 2014, 14, 76-82. [CrossRef]
118. Juhnke, M.; John, E. Wet-media milling of colloidal drug suspensions stabilized by means of charged nanoparticles. Chem. Eng. Technol. 2012, 35, 1931-1940. [CrossRef]
119. Kawatra, S.K. Advances in Comminution; Society for Mining, Metallurgy and Exploration: Englewood, CO, USA, 2006.
120. Afolabi, A. Batch and Continuous Production of Stable Dense Suspensions of Drug Nanoparticles in aWet Stirred Media Mill. Ph.D. Thesis, New Jersey Institute of Technology, Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, Newark, NJ, USA, 2013.
121. Hennart, S.; Domingues, M.; Wildeboer, W.; van Hee, P.; Meesters, G. Study of the process of stirred ball milling of poorly water soluble organic products using factorial design. Powder Technol. 2010, 198, 56-60. [CrossRef]
122. Kumar, S.; Burgess, D. J. Wet milling induced physical and chemical instabilities of naproxen nano-crystalline suspensions. Int. J. Pharm. 2014, 466, 223-232. [CrossRef] [PubMed]
123. Juhnke, M.; Märtin, D.; John, E. Generation of wear during the production of drug nanosuspensions by wet media milling. Eur. J. Pharm. Biopharm. 2012, 81, 214-222. [CrossRef] [PubMed]
124. Singare, D.S.; Marella, S.; Gowthamrajan, K.; Kulkarni, G.T.; Vooturi, R.; Rao, P.S. Optimization of formulation and process variable of nanosuspension: An industrial perspective. Int. J. Pharm. 2010, 402, 213-220. [CrossRef] [PubMed]
125. Bilgili, E.; Hamey, R.; Scarlett, B. Production of pigment nanoparticles using a wet stirred mill with polymeric media. China Particuol. 2004, 2, 93-100. [CrossRef]
126. Knieke, C.; Sommer, M.; Peukert, W. Identifying the apparent and true grinding limit. Powder Technol. 2009, 195, 25-30. [CrossRef]
127. Prasher, C.L. Crushing and Grinding Process Handbook; John Wiley & Sons Ltd.: Chichester, NY, USA, 1987.
128. Gahn, C.; Mersmann, A. Brittle fracture in crystallization processes part A. Attrition and abrasion of brittle solids. Chem. Eng. Sci. 1999, 54, 1273-1282. [CrossRef]
129. Gahn, C.; Mersmann, A. Brittle fracture in crystallization processes part B. Growth of fragments and scale-up of suspension crystallizers. Chem. Eng. Sci. 1999, 54, 1283-1292. [CrossRef]
130. Ghadiri, M.; Zhang, Z. Impact attrition of particulate solids. Part 1: A theoretical model of chipping. Chem. Eng. Sci. 2002, 57, 3659-3669. [CrossRef]
131. Vogel, L.; Peukert, W. Breakage behaviour of different materials-Construction of a mastercurve for the breakage probability. Powder Technol. 2003, 129, 101-110. [CrossRef]
132. Meier, M.; John, E.; Wieckhusen, D.; Wirth, W.; Peukert, W. Influence of mechanical properties on impact fracture: Prediction of the milling behaviour of pharmaceutical powders by nanoindentation. Powder Technol. 2009, 188, 301-313. [CrossRef]
133. Lawn, B.; Marshall, D. Hardness, toughness, and brittleness: An indentation analysis. J. Am. Ceram. Soc. 1979, 62, 347-350. [CrossRef]
134. Meier, M.; John, E.; Wieckhusen, D.; Wirth, W.; Peukert, W. Generally applicable breakage functions derived from single particle comminution data. Powder Technol. 2009, 194, 33-41. [CrossRef]
135. Box, G.E.P.; Wilson, K.B. On the experimental attainment of optimum conditions. J. R. Stat. Soc. Ser. B 1951, 13, 1-45.
136. Bilgili, E.; Arastoopour, H.; Bernstein, B.; Hamey, R. Some novel applications of grinding and milling technologies: Milling of soft materials and nanomilling. In Fine Particle Technology and Characterization; Yekeler, M., Ed.; Research Signpost: Kerala, India, 2008; pp. 41-67.
137. Capece, M.; Bilgili, E.; Davé, R.N. Formulation of a physically motivated specific breakage rate parameter for ball milling via the discrete element method. AIChE J. 2014, 60, 2404-2415. [CrossRef]
138. Gudin, D.; Turczyn, R.; Mio, H.; Kano, J.; Saito, F. Simulation of the movement of beads by the dem with respect to the wet grinding process. AIChE J. 2006, 52, 3421-3426. [CrossRef]
139. Knieke, C.; Steinborn, C.; Romeis, S.; Peukert, W.; Breitung-Faes, S.; Kwade, A. Nanoparticle production with stirred-media mills: Opportunities and limits. Chem. Eng. Technol. 2010, 33, 1401-1411. [CrossRef]
140. Sommer, M.; Stenger, F.; Peukert, W.; Wagner, N.J. Agglomeration and breakage of nanoparticles in stirred media mills-A comparison of different methods and models. Chem. Eng. Sci. 2006, 61, 135-148. [CrossRef]
141. Annapragada, A.; Adjei, A. Numerical simulation of milling processes as an aid to process design. Int. J. Pharm. 1996, 136, 1-11. [CrossRef]
142. Kwade, A. Determination of the most important grinding mechanism in stirred media mills by calculating stress intensity and stress number. Powder Technol. 1999, 105, 382-388. [CrossRef]
143. Tuzcu, E.T.; Rajamani, R.K. Modeling breakage rates in mills with impact energy spectra and ultra fast load cell data. Miner. Eng. 2011, 24, 252-260. [CrossRef]
144. Graeme, L. CFD modelling of a stirred bead mill for fine grinding. In Proceedings of the Second International Conference on CFD in the Minerals and Process Industries, Melbourne, Australia, 6-8 December 1999; pp. 449-454.
145. Gers, R.; Climent, E.; Legendre, D.; Anne-Archard, D.; Frances, C. Numerical modelling of grinding in a stirred media mill: Hydrodynamics and collision characteristic. Chem. Eng. Sci. 2010, 65, 2052-2064. [CrossRef]
146. Gers, R.; Anne-Archard, D.; Climent, E.; Legendre, D.; Frances, C. Two colliding grinding beads: Experimental flow fields and particle capture efficiency. Chem. Eng. Technol. 2010, 33, 1438-1446. [CrossRef]
147. Rosenkranz, S.; Breitung-Faes, S.; Kwade, A. Experimental investigations and modelling of the ball motion in planetary ball mills. Powder Technol. 2011, 212, 224-230. [CrossRef]
148. Cundall, P.A.; Strack, O.D. A discrete numerical model for granular assemblies. Geotechnique 1979, 29, 47-65. [CrossRef]
149. Khanal, M.; Schubert, W.; Tomas, J. Oblique impact simulations of high strength agglomerates. In Micro-Macro-Interaction; Springer: Berlin, Germany, 2008; pp. 243-253.
150. Mishra, B. A review of computer simulation of tumbling mills by the discrete element method: Part II-Practical applications. Int. J. Miner. Process. 2003, 71, 95-112. [CrossRef]
151. Mori, H.; Mio, H.; Kano, J.; Saito, F. Ball mill simulation in wet grinding using a tumbling mill and its correlation to grinding rate. Powder Technol. 2004, 143, 230-239. [CrossRef]
152. Van Buijtenen, M.S.; Deen, N.G.; Heinrich, S.; Antonyuk, S.; Kuipers, J. A discrete element study of wet particle-particle interaction during granulation in a spout fluidized bed. Can. J. Chem. Eng. 2009, 87, 308-317. [CrossRef]
153. Stražišar, J.; Runovc, F. Kinetics of comminution in micro-and sub-micrometer ranges. Int. J. Miner. Process. 1996, 44, 673-682. [CrossRef]
154. Varinot, C.; Berthiaux, H.; Dodds, J. Prediction of the product size distribution in associations of stirred bead mills. Powder Technol. 1999, 105, 228-236. [CrossRef]
155. Cho, H.; Waters, M.; Hogg, R. Investigation of the grind limit in stirred-media milling. Int. J. Miner. Process. 1996, 44, 607-615. [CrossRef]
156. Bilgili, E.; Scarlett, B. Population balance modeling of non-linear effects in milling processes. Powder Technol. 2005, 153, 59-71. [CrossRef]
157. Bilgili, E. On the consequences of non-first-order breakage kinetics in comminution processes: Absence of self-similar size spectra. Part. Part. Syst. Charact. 2007, 24, 12-17. [CrossRef]
158. Bilgili, E.; Yepes, J.; Scarlett, B. Formulation of a non-linear framework for population balance modeling of batch grinding: Beyond first-order kinetics. Chem. Eng. Sci. 2006, 61, 33-44. [CrossRef]
159. Capece, M.; Bilgili, E.; Dave, R. Identification of the breakage rate and distribution parameters in a non-linear population balance model for batch milling. Powder Technol. 2011, 208, 195-204. [CrossRef]
160. Heim, A.; Leszczyniecki, R.; Amanowicz, K. Determination of parameters for wet-grinding model in perl mills. Powder Technol. 1985, 41, 173-179. [CrossRef]
161. Hennart, S.; Wildeboer, W.; van Hee, P.; Meesters, G. Identification of the grinding mechanisms and their origin in a stirred ball mill using population balances. Chem. Eng. Sci. 2009, 64, 4123-4130. [CrossRef]
162. Bilgili, E.; Hamey, R.; Scarlett, B. Nano-milling of pigment agglomerates using a wet stirred media mill: Elucidation of the kinetics and breakage mechanisms. Chem. Eng. Sci. 2006, 61, 149-157. [CrossRef]
163. Hänchen, M.; Krevor, S.; Mazzotti, M.; Lackner, K.S. Validation of a population balance model for olivine dissolution. Chem. Eng. Sci. 2007, 62, 6412-6422. [CrossRef]
164. Somasundaran, P.; Runkana, V. Modeling flocculation of colloidal mineral suspensions using population balances. Int. J. Miner. Process. 2003, 72, 33-55. [CrossRef]
165. Hounslow, M. The population balance as a tool for understanding particle rate processes. KONA Powder Part J. 1998, 16, 179-193. [CrossRef]
166. Varinot, C.; Hiltgun, S.; Pons, M.-N.; Dodds, J. Identification of the fragmentation mechanisms in wet-phase fine grinding in a stirred bead mill. Chem. Eng. Sci. 1997, 52, 3605-3612. [CrossRef]
167. Eskin, D.; Zhupanska, O.; Hamey, R.; Moudgil, B.; Scarlett, B. Microhydrodynamic analysis of nanogrinding in stirred media mills. AIChE J. 2005, 51, 1346-1358. [CrossRef]
168. Gidaspow, D. Multiphase Flow and Fluidization: Continuum and Kinetic Theory Descriptions; Academic Press: Salt Lake City, UT, USA, 1994.
169. Eskin, D.; Miller, M.J. A model of non-newtonian slurry flow in a fracture. Powder Technol. 2008, 182, 313-322. [CrossRef]
170. Hall, M. Encyclopedia of Nanoscience and Nanotechnology; American Scientific Publishers: Valencia, CA, USA, 2010.
171. Xiong, R.; Lu, W.; Li, J.; Wang, P.; Xu, R.; Chen, T. Preparation and characterization of intravenously injectable nimodipine nanosuspension. Int. J. Pharm. 2008, 350, 338-343. [CrossRef] [PubMed]
172. Sinha, B.; Müller, R.H.; Möschwitzer, J.P. Bottom-up approaches for preparing drug nanocrystals: Formulations and factors affecting particle size. Int. J. Pharm. 2013, 453, 126-141. [CrossRef] [PubMed]
173. Ajazuddin, S.S. Applications of novel drug delivery system for herbal formulations. Fitoterapia 2010, 81, 680-689. [CrossRef] [PubMed]
174. Mukerjee, A.; Vishwanatha, J.K. Formulation, characterization and evaluation of curcumin-loaded plga nanospheres for cancer therapy. Anticancer Res. 2009, 29, 3867-3875. [PubMed]
175. Chamarthy, S.P.; Pinal, R. The nature of crystal disorder in milled pharmaceutical materials. Colloids Surf. A 2008, 331, 68-75. [CrossRef]
176. Feng, T.; Pinal, R.; Carvajal, M.T. Process induced disorder in crystalline materials: Differentiating defective crystals from the amorphous form of griseofulvin. J. Pharm. Sci. 2008, 97, 3207-3221. [CrossRef] [PubMed]
177. Otte, A.; Carvajal, M.T. Assessment of milling-induced disorder of two pharmaceutical compounds. J. Pharm. Sci. 2011, 100, 1793-1804. [CrossRef] [PubMed]
178. Wildfong, P.L.; Hancock, B.C.; Moore, M.D.; Morris, K.R. Towards an understanding of the structurally based potential for mechanically activated disordering of small molecule organic crystals. J. Pharm. Sci. 2006, 95, 2645-2656. [CrossRef] [PubMed]
179. Howorth, C.; Lee, W.; Rainforth, W.; Messer, P. Contamination rates from Ce-and Y-TZP ball milling media. Br. Ceram. Trans. J. 1991, 90, 18-21.
180. Czekai, D.A.; Seaman, L.P. Continuously Feeding Therapeutical or Imaging Agents and Rigid Grinding Media to a Milling Chamber, Contacting the Agent with Grinding Media to Reduce Particle Size, Continuously Removing and Separating. U.S. Patent 5,718,388, 17 February 1998.
181. Plumb, K. Continuous processing in the pharmaceutical industry: Changing the mind set. Chem. Eng. Res. Des. 2005, 83, 730-738. [CrossRef]
182. Mannheim, V. Empirical and scale-up modeling in stirred ball mills. Chem. Eng. Res. Des. 2011, 89, 405-409. [CrossRef]
183. Wagener, P.; Lau, M.; Breitung-Faes, S.; Kwade, A.; Barcikowski, S. Physical fabrication of colloidal ZnO nanoparticles combining wet-grinding and laser fragmentation. Appl. Phys. A 2012, 108, 793-799. [CrossRef]
184. Patel, C.M.; Chakraborty, M.; Murthy, Z.V.P. Preparation of fenofibrate nanoparticles by combined stirred media milling and ultrasonication method. Ultrason. Sonochem. 2014, 21, 1100-1107. [CrossRef] [PubMed]
185. Kipp, J.E.; Wong, J.C.T.; Doty, M.J.; Rebbeck, C.L. Microprecipitation Method for Preparing Submicron Suspensions. U.S. Patent 6,607,784, 19 August 2003.
186. Rabinow, B.; Kipp, J.; Papadopoulos, P.; Wong, J.; Glosson, J.; Gass, J.; Sun, C.-S.; Wielgos, T.; White, R.; Cook, C. Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int. J. Pharm. 2007, 339, 251-260. [CrossRef] [PubMed]
187. Shelar, D.B.; Pawar, S.K.; Vavia, P.R. Fabrication of isradipine nanosuspension by anti-solvent microprecipitation-high-pressure homogenization method for enhancing dissolution rate and oral bioavailability. Drug Deliv. Transl. Res. 2013, 3, 384-391. [CrossRef] [PubMed]
188. Petersen, R. Nanocrystals for Use in Topical Cosmetic Formulations and Method of Production Thereof. U.S. Patent 9,114,077, 25 August 2015.