Drug Nanocrystals: A Comprehensive Review with Current Regulatory Guidelines

Author(s): Mori Dhaval*, Jalpa Makwana, Ekta Sakariya, Kiran Dudhat

Journal Name: Current Drug Delivery

Volume 17 , Issue 6 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Drug nanocrystals offer an attractive approach for improving the solubility and dissolution rate of poorly soluble drugs which accounts for nearly 40 % newly discovered drug molecules. Both methods for manufacturing drug nanocrystals have high industrial acceptability for being simple and easy to scale which is evident from the number of approved products available in the market. Ability to modify multiple aspects of dosage form like bioavailability, release pattern and dosage form requirement along with flexibility in choosing final dosage form starting from the tablet, capsule, suspension to parenteral one, have made nanocrystal technology one of the very promising and adaptable technology for dosage form design.

Keywords: Drug nanocrystals, manufacturing methods, physical and chemical stability, regulatory guideline, marketed products, bioavailability.

Thassu, D.; Deleers, M.; Pathak, Y.V. Nanoparticulate drug delivery systems. CRC Press, Taylor and Francis Group. 2007, pp.376.
Keck, C.M.; Müller, R.H. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur. J. Pharm. Biopharm., 2006, 62(1), 3-16.
[http://dx.doi.org/10.1016/j.ejpb.2005.05.009] [PMID: 16129588]
Gupta, R.B.; Kompella, U.B. Nanoparticle technology for drug delivery; CRC Press, Taylor and Francis, 2006, p. 416.
Shegokar, R.; Müller, R.H. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int. J. Pharm., 2010, 399(1-2), 129-139.
[http://dx.doi.org/10.1016/j.ijpharm.2010.07.044] [PMID: 20674732]
Weissig, V.; Pettinger, T.K.; Murdock, N. Nanopharmaceuticals (part 1): products on the market. Int. J. Nanomedicine, 2014, 9, 4357-4373.
[http://dx.doi.org/10.2147/IJN.S46900] [PMID: 25258527]
Junghanns, J-U.A.; Müller, R.H. Nanocrystal technology, drug delivery and clinical applications. Int. J. Nanomedicine, 2008, 3(3), 295-309.
[PMID: 18990939]
Hasegawa, Y.; Higashi, K.; Yamamoto, K.; Moribe, K. Direct evaluation of molecular states of piroxicam/poloxamer nanosuspension by suspended-state NMR and Raman spectroscopies. Mol. Pharm., 2015, 12(5), 1564-1572.
[http://dx.doi.org/10.1021/mp500872g] [PMID: 25849345]
Jog, R.; Burgess, D.J. Pharmaceutical amorphous nanoparti-cles. J. Pharm. Sci., 2017, 106(1), 39-65.
[http://dx.doi.org/10.1016/j.xphs.2016.09.014] [PMID: 27816266]
Tran, T.T-D.; Tran, P.H-L.; Nguyen, M.N.U.; Tran, K.T.M.; Pham, M.N.; Tran, P.C.; Vo, T.V. Amorphous isradipine nanosuspension by the sonoprecipitation method. Int. J. Pharm., 2014, 474(1-2), 146-150.
[http://dx.doi.org/10.1016/j.ijpharm.2014.08.017] [PMID: 25138256]
Siepmann, J.; Siepmann, F. Mathematical modeling of drug dissolution. Int. J. Pharm., 2013, 453(1), 12-24.
[http://dx.doi.org/10.1016/j.ijpharm.2013.04.044] [PMID: 23618956]
Hecq, J.; Deleers, M.; Fanara, D.; Vranckx, H.; Amighi, K. Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. Int. J. Pharm., 2005, 299(1-2), 167-177.
[http://dx.doi.org/10.1016/j.ijpharm.2005.05.014] [PMID: 15996838]
Baka, E.; Comer, J.E.; Takács-Novák, K. Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J. Pharm. Biomed. Anal., 2008, 46(2), 335-341.
[http://dx.doi.org/10.1016/j.jpba.2007.10.030] [PMID: 18055153]
Bhattachar, S.N.; Deschenes, L.A.; Wesley, J.A. Solubility: it’s not just for physical chemists. Drug Discov. Today, 2006, 11(21-22), 1012-1018.
[http://dx.doi.org/10.1016/j.drudis.2006.09.002] [PMID: 17055411]
Junyaprasert, V.B.; Morakul, B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J. Pharmaceut. Sci., 2015, 10, 13-23.
Kesisoglou, F.; Panmai, S.; Wu, Y. Nanosizing--oral formulation development and biopharmaceutical evaluation. Adv. Drug Deliv. Rev., 2007, 59(7), 631-644.
[http://dx.doi.org/10.1016/j.addr.2007.05.003] [PMID: 17601629]
Kocbek, P.; Baumgartner, S.; Kristl, J. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int. J. Pharm., 2006, 312(1-2), 179-186.
[http://dx.doi.org/10.1016/j.ijpharm.2006.01.008] [PMID: 16469459]
Khadka, P.; Ro, J.; Kim, H.; Kim, I.; Kim, J.T.; Kim, H.; Cho, J.M.; Yun, G.; Lee, J. Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability Asian. J. Pharm. Sci., 2014, 9, 304-316.
Tuomela, A.; Saarinen, J.; Strachan, C.J.; Hirvonen, J.; Peltonen, L. Production, applications and in vivo fate of drug nano-crystals. J. Drug Deliv. Sci. Technol., 2016, 34, 21-31.
Smart, J.D. The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev., 2005, 57(11), 1556-1568.
[http://dx.doi.org/10.1016/j.addr.2005.07.001] [PMID: 16198441]
Rabinow, B.E. Nanosuspensions in drug delivery. Nat. Rev. Drug Discov., 2004, 3(9), 785-796.
[http://dx.doi.org/10.1038/nrd1494] [PMID: 15340388]
Che, E.; Zheng, X.; Sun, C.; Chang, D.; Jiang, T.; Wang, S. Drug nanocrystals: a state of the art formulation strategy for preparing the poorly water-soluble drugs. Asian. J. Pharm. Sci., 2012, 7(2), 85-95.
Bruno, R.P.; Mcilwrick, R. Microfluidizer® processor technology for high performance particle size reduction, mixing and dispersion. Paperback APV, 2001, 42, 77-89.
de Waard, H.; Frijlink, H.W.; Hinrichs, W.L. Bottom-up preparation techniques for nanocrystals of lipophilic drugs. Pharm. Res., 2011, 28(5), 1220-1223.
[http://dx.doi.org/10.1007/s11095-010-0323-3] [PMID: 21086152]
Patravale, V.B.; Date, A.A.; Kulkarni, R.M. Nanosuspensions: a promising drug delivery strategy. J. Pharm. Pharmacol., 2004, 56(7), 827-840.
[http://dx.doi.org/10.1211/0022357023691] [PMID: 15233860]
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(1), 64-75.
[http://dx.doi.org/10.1016/j.ijpharm.2008.07.023] [PMID: 18721869]
Hu, J.; Johnston, K.P.; Williams, R.O., III Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev. Ind. Pharm., 2004, 30(3), 233-245.
[http://dx.doi.org/10.1081/DDC-120030422] [PMID: 15109023]
Möschwitzer, J.P. Drug nanocrystals in the commercial pharmaceutical development process. Int. J. Pharm., 2013, 453(1), 142-156.
[http://dx.doi.org/10.1016/j.ijpharm.2012.09.034] [PMID: 23000841]
Malamatari, M.; Taylor, K.M.G.; Malamataris, S.; Douroumis, D.; Kachrimanis, K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov. Today, 2018, 23(3), 534-547.
[http://dx.doi.org/10.1016/j.drudis.2018.01.016] [PMID: 29326082]
Chen, M.J.; Hui, H-W.; Lee, T.; Kurtulik, P.; Surapaneni, S. Nanosuspension of a poorly soluble drug via microfluidization process; Google Patents, 2015.
Müller, R.; Jacobs, C.; Kayser, O. Disso Cubes: A novel for-mulation for poorly soluble and poorly bioavailable drugs. Rathbone M, Hadgraft J, Roberts M: Modified-release drug delivery technology; Informa Healthcare, 2002, pp. 135-149.
Bushrab, N.; Müller, R. Nanocrystals of poorly soluble drugs for oral administration. J. New Drugs, 2003, 5, 20-26.
Katteboinaa, S.; Chandrasekhar, V.; Balaji, S. Drug nanocrystals: a novel formulation approach for poorly soluble drugs. Int. J. Pharm. Tech. Res., 2009, 1, 682-694.
Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv. Drug Deliv. Rev., 2001, 47(1), 65-81.
[http://dx.doi.org/10.1016/S0169-409X(00)00122-8] [PMID: 11251246]
Kipp, J.E.; Wong, J.C.T.; Doty, M.J.; Rebbeck, C.L. Microprecipitation method for preparing submicron suspensions; Google Patents, 2003.
Müller, R.; Möschwitzer, J. Method and apparatus for the production of ultrafine particles and coating of such particles 2005, pp.053.
Jacobs, C.; Kayser, O.; Müller, R.H. Production and characterisation of mucoadhesive nanosuspensions for the formulation of bupravaquone. Int. J. Pharm., 2001, 214(1-2), 3-7.
[http://dx.doi.org/10.1016/S0378-5173(00)00622-0] [PMID: 11282227]
Kipp, J.E. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int. J. Pharm., 2004, 284(1-2), 109-122.
[http://dx.doi.org/10.1016/j.ijpharm.2004.07.019] [PMID: 15454302]
Choi, J-Y.; Yoo, J.Y.; Kwak, H-S.; Nam, B.U.; Lee, J. Role of polymeric stabilizers for drug nanocrystal dispersions. Curr. Appl. Phys., 2005, 5, 472-474.
Chun, Zeng. H. Ostwald ripening: a synthetic approach for hollow nanomaterials. Curr. Nanosci., 2007, 3, 177-181.
Muller, R.H.; Keck, C.M. Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles. J. Biotechnol., 2004, 113(1-3), 151-170.
[http://dx.doi.org/10.1016/j.jbiotec.2004.06.007] [PMID: 15380654]
Kulshreshtha, A.K.; Singh, O.N.; Wall, G.M. Pharmaceutical suspensions: from formulation development to manufacturing; Springer, 2009, p. 328.
Gao, L.; Zhang, D.; Chen, M. 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.
Kim, C. Surface chemistry and colloids, advanced pharmaceutics: physicochemical principles; CRC: Boca Raton, 2004, pp. 193-256.
Carstensen, J.T. Advanced pharmaceutical solids; CRC Press, Taylor and Francis, 2000, p. 536.
Lindfors, L.; Skantze, P.; Skantze, U.; Westergren, J.; Olsson, U. Amorphous drug nanosuspensions. 3. Particle dissolution and crystal growth. Langmuir, 2007, 23(19), 9866-9874.
[http://dx.doi.org/10.1021/la700811b] [PMID: 17696457]
Sawant, S.V.; Kadam, D.; Jadhav, D.; Sankpal, S.V. Drug nano-crystals: novel technique for delivery of poorly soluble drugs. Int. J. Sci. Innov. Discov., 2011, 1, 1-15.
Bhattacharjee, S. DLS and zeta potential - What they are and what they are not? J. Control. Release, 2016, 235, 337-351.
[http://dx.doi.org/10.1016/j.jconrel.2016.06.017] [PMID: 27297779]
Honary, S.; Zahir, F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 1). Trop. J. Pharm. Res., 2013, 12, 255-264.
Mishra, P.R.; Al Shaal, L.; Müller, R.H.; Keck, C.M. Production and characterization of Hesperetin nanosuspensions for dermal delivery. Int. J. Pharm., 2009, 371(1-2), 182-189.
[http://dx.doi.org/10.1016/j.ijpharm.2008.12.030] [PMID: 19162147]
Clogston, J.D.; Patri, A.K. Zeta potential measurement, Characterization of nanoparticles intended for drug delivery; Springer, 2011, pp. 63-70.
Wu, L.; Zhang, J.; Watanabe, W. Physical and chemical stability of drug nanoparticles. Adv. Drug Deliv. Rev., 2011, 63(6), 456-469.
[http://dx.doi.org/10.1016/j.addr.2011.02.001] [PMID: 21315781]
Kuentz, M.; Röthlisberger, D. Rapid assessment of sedimentation stability in dispersions using near infrared transmission measurements during centrifugation and oscillatory rheology. Eur. J. Pharm. Biopharm., 2003, 56(3), 355-361.
[http://dx.doi.org/10.1016/S0939-6411(03)00108-5] [PMID: 14602177]
Gao, L.; Liu, G.; Ma, J.; Wang, X.; Zhou, L.; Li, X. Drug nanocrystals: in vivo performances. J. Control. Release, 2012, 160(3), 418-430.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.013] [PMID: 22465393]
Kayser, O.; Olbrich, C.; Yardley, V.; Kiderlen, A.F.; Croft, S.L. Formulation of amphotericin B as nanosuspension for oral administration. Int. J. Pharm., 2003, 254(1), 73-75.
[http://dx.doi.org/10.1016/S0378-5173(02)00686-5] [PMID: 12615413]
Mauludin, R.; Müller, R.H.; Keck, C.M. Development of an oral rutin nanocrystal formulation. Int. J. Pharm., 2009, 370(1-2), 202-209.
[http://dx.doi.org/10.1016/j.ijpharm.2008.11.029] [PMID: 19114097]
Mitri, K.; Shegokar, R.; Gohla, S.; Anselmi, C.; Müller, R.H. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int. J. Pharm., 2011, 420(1), 141-146.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.026] [PMID: 21884768]
Zhang, J.; Lv, H.; Jiang, K.; Gao, Y. Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal. Int. J. Pharm., 2011, 420(1), 180-188.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.023] [PMID: 21878378]
Ige, P.P.; Baria, R.K.; Gattani, S.G. Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability. Colloids Surf. B Biointerfaces, 2013, 108, 366-373.
[http://dx.doi.org/10.1016/j.colsurfb.2013.02.043] [PMID: 23602990]
Fu, Q.; Sun, J.; Zhang, D.; Li, M.; Wang, Y.; Ling, G.; Liu, X.; Sun, Y.; Sui, X.; Luo, C.; Sun, L.; Han, X.; Lian, H.; Zhu, M.; Wang, S.; He, Z. Nimodipine nanocrystals for oral bioavailability improvement: preparation, characterization and pharmacokinetic studies. Colloids Surf. B Biointerfaces, 2013, 109, 161-166.
[http://dx.doi.org/10.1016/j.colsurfb.2013.01.066] [PMID: 23668980]
Müller, R.H.; Jacobs, C. Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. Int. J. Pharm., 2002, 237(1-2), 151-161.
[http://dx.doi.org/10.1016/S0378-5173(02)00040-6] [PMID: 11955813]
Li, W.; Yang, Y.; Tian, Y.; Xu, X.; Chen, Y.; Mu, L.; Zhang, Y.; Fang, L. Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension. Int. J. Pharm., 2011, 408(1-2), 157-162.
[http://dx.doi.org/10.1016/j.ijpharm.2011.01.059] [PMID: 21295124]
Hu, L.; Kong, D.; Hu, Q.; Gao, N.; Pang, S. evaluation of high-performance curcumin nanocrystals for pulmonary drug delivery both in vitro and in vivo. Nanoscale Res. Lett., 2015, 10, 381.
Hu, X.; Yang, F-F.; Wei, X.L.; Yao, G.Y.; Liu, C-Y.; Zheng, Y.; Liao, Y.H. Curcumin acetate nanocrystals for sustained pulmonary delivery: preparation, characterization and in vivo evaluation. J. Biomed. Nanotechnol., 2017, 13(1), 99-09.
[http://dx.doi.org/10.1166/jbn.2017.2326] [PMID: 29373003]
Ostrander, K.D.; Bosch, H.W.; Bondanza, D.M. An in-vitro assessment of a NanoCrystal beclomethasone dipropionate colloidal dispersion via ultrasonic nebulization. Eur. J. Pharm. Biopharm., 1999, 48(3), 207-215.
[http://dx.doi.org/10.1016/S0939-6411(99)00049-1] [PMID: 10612031]
Jacobs, C.; Müller, R.H. Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharm. Res., 2002, 19(2), 189-194.
[http://dx.doi.org/10.1023/A:1014276917363] [PMID: 11883646]
Merisko-Liversidge, E.; Liversidge, G.G.; Cooper, E.R. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur. J. Pharm. Sci., 2003, 18(2), 113-120.
[http://dx.doi.org/10.1016/S0928-0987(02)00251-8] [PMID: 12594003]
Sun, B.; Yeo, Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr. Opin. Solid State Mater. Sci., 2012, 16(6), 295-301.
[http://dx.doi.org/10.1016/j.cossms.2012.10.004] [PMID: 23645994]
Chen, L.; Wang, Y.; Zhang, J.; Hao, L.; Guo, H.; Lou, H.; Zhang, D. Bexarotene nanocrystal-Oral and parenteral formulation development, characterization and pharmacokinetic evaluation. Eur. J. Pharm. Biopharm., 2014, 87(1), 160-169.
[http://dx.doi.org/10.1016/j.ejpb.2013.12.005] [PMID: 24333772]
Liversidge, G.G.; Engers, D.A.; Roberts, M.E.; Ruddy, S.B.; Wong, S.M.; Xu, S. Nanocrystalline formulations of Human Immunodeficiency Virus (HIV) protease inhibitors using cellulosic surface stabilizers; Google Patents, 2000.
Ganta, S.; Paxton, J.W.; Baguley, B.C.; Garg, S. Formulation and pharmacokinetic evaluation of an asulacrine nanocrystalline suspension for intravenous delivery. Int. J. Pharm., 2009, 367(1-2), 179-186.
[http://dx.doi.org/10.1016/j.ijpharm.2008.09.022] [PMID: 18848873]
Peters, K.; Leitzke, S.; Diederichs, J.E.; Borner, K.; Hahn, H.; Müller, R.H.; Ehlers, S. Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. J. Antimicrob. Chemother., 2000, 45(1), 77-83.
[http://dx.doi.org/10.1093/jac/45.1.77] [PMID: 10629016]
Das, S.; Suresh, P.K. Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to amphotericin B. Nanomedicine (Lond.), 2011, 7(2), 242-247.
[http://dx.doi.org/10.1016/j.nano.2010.07.003] [PMID: 20692375]
Romero, G.B.; Keck, C.M.; Müller, R.H.; Bou-Chacra, N.A. Development of cationic nanocrystals for ocular delivery. Eur. J. Pharm. Biopharm., 2016, 107, 215-222.
[http://dx.doi.org/10.1016/j.ejpb.2016.07.005] [PMID: 27388629]
Ali, H.S.; York, P.; Ali, A.M.; Blagden, N. Hydrocortisone nanosuspensions for ophthalmic delivery: a comparative study between microfluidic nanoprecipitation and wet milling. J. Control. Release, 2011, 149(2), 175-181.
[http://dx.doi.org/10.1016/j.jconrel.2010.10.007] [PMID: 20946923]
Kassem, M.A.; Abdel Rahman, A.A.; Ghorab, M.M.; Ahmed, M.B.; Khalil, R.M. Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int. J. Pharm., 2007, 340(1-2), 126-133.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.011] [PMID: 17600645]
Pelikh, O.; Stahr, P-l.; Huang, J.; Geisel, N.; Keck, C.M.; Gerst, M.; Scholz, P.; Dietrich, H. Nanocrystals for improved dermal drug delivery. Eur. J. Pharm. Biopharm., 2018, 128, 170-178.
Lademann, J.; Richter, H.; Teichmann, A.; Otberg, N.; Blume-Peytavi, U.; Luengo, J.; Weiss, B.; Schaefer, U.F.; Lehr, C-M.; Wepf, R.; Sterry, W. Nanoparticles--an efficient carrier for drug delivery into the hair follicles. Eur. J. Pharm. Biopharm., 2007, 66(2), 159-164.
[http://dx.doi.org/10.1016/j.ejpb.2006.10.019] [PMID: 17169540]
Pireddu, R.; Caddeo, C.; Valenti, D.; Marongiu, F.; Scano, A.; Ennas, G.; Lai, F.; Fadda, A.M.; Sinico, C. Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability. Colloids Surf. B Biointerfaces, 2016, 143, 64-70.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.026] [PMID: 26998867]
Vidlářová, L.; Romero, G.B.; Hanuš, J.; Štěpánek, F.; Müller, R.H. Nanocrystals for dermal penetration enhancement - Effect of concentration and underlying mechanisms using curcumin as model. Eur. J. Pharm. Biopharm., 2016, 104, 216-225.
[http://dx.doi.org/10.1016/j.ejpb.2016.05.004] [PMID: 27163241]
Al Shaal, L.; Shegokar, R.; Müller, R.H. Production and characterization of antioxidant apigenin nanocrystals as a novel UV skin protective formulation. Int. J. Pharm., 2011, 420(1), 133-140.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.018] [PMID: 21871547]
Hussaarts, L.; Mühlebach, S.; Shah, V.P.; McNeil, S.; Borchard, G.; Flühmann, B.; Weinstein, V.; Neervannan, S.; Griffiths, E.; Jiang, W.; Wolff-Holz, E.; Crommelin, D.J.A.; de Vlieger, J.S.B. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks. Ann. N. Y. Acad. Sci., 2017, 1407(1), 39-49.
[http://dx.doi.org/10.1111/nyas.13347] [PMID: 28445611]
Chen, M.L.; John, M.; Lee, S.L.; Tyner, K.M. Development considerations for nanocrystal drug products. AAPS J., 2017, 19(3), 642-651.
[http://dx.doi.org/10.1208/s12248-017-0064-x] [PMID: 28281194]
Mühlebach, S. Regulatory challenges of nanomedicines and their follow-on versions: a generic or similar approach? Adv. Drug Deliv. Rev., 2018, 131, 122-131.
[http://dx.doi.org/10.1016/j.addr.2018.06.024] [PMID: 29966685]
F.A., Services; H, Ed. D.A U.S. Department of Health and Human Services, Center for Drug Evaluation and Research, Determining Whether to Submit an ANDA or a 505(b)(2) Application Guidance for Industry in U.S.D.
Aoyagi, N.; Ogata, H.; Kaniwa, N.; Ejima, A. Effect of food on the bioavailability of Griseofulvin from microsize and PEG ultramicrosize (GRIS-PEG) plain tablets. J. Pharmacobiodyn., 1982, 5(2), 120-124.
[http://dx.doi.org/10.1248/bpb1978.5.120] [PMID: 7097474]
Möschwitzer, J.; Müller, R. From the drug nanocrystal to the final mucoadhesive oral dosage form. Int. Meeting, 2004, p. 88.
Femia, R.A. Megestrol acetate nanocrystal oral suspension: results of dose-escalating studies under fed and fasting conditions National HIV/AIDS Update Conference, Oakland, California2005.
Ahmad, S.; Roy, A.; Angela Lewis, S. New-generation antipsy-chotics: long-acting injectable formulations and drug-delivery technologies. Int. J. Sci. Res. (Ahmedabad), 2015, 4, 367-372.
Chastain, J.E.; Sanders, M.E.; Curtis, M.A.; Chemuturi, N.V.; Gadd, M.E.; Kapin, M.A.; Markwardt, K.L.; Dahlin, D.C. Distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye. Exp. Eye Res., 2016, 145, 58-67.
[http://dx.doi.org/10.1016/j.exer.2015.10.009] [PMID: 26474497]
Ventola, C.L. Progress in nanomedicine: approved and investigational nanodrugs. P T, 2017, 42(12), 742-755.
[PMID: 29234213]
Ehret, M.J.; Davis, E.; Luttrell, S.E.; Clark, C. Aripiprazole lauroxil nanoCrystal® dispersion technology (Aristada Initio®). Clin. Schizophr. Relat. Psychoses, 2018, 12(2), 92-96.
[http://dx.doi.org/10.3371/CSRP.EHDA071918] [PMID: 30040476]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 06 August, 2020
Page: [470 - 482]
Pages: 13
DOI: 10.2174/1567201817666200512104833
Price: $65

Article Metrics

PDF: 29