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Critical Reviews™ in Therapeutic Drug Carrier Systems
IF: 2.9 5-Year IF: 3.72 SJR: 0.736 SNIP: 0.818 CiteScore™: 4.6

ISSN Print: 0743-4863
ISSN Online: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.2020032040
pages 229-269

Systematic Development of Drug Nanocargos Using Formulation by Design (FbD): An Updated Overview

Bhupinder Singh
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160014; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, India 160014
Teenu Sharma
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160014
Sumant Saini
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160014
Ranjot Kaur
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160014; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom
Atul Jain
UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, India 160014
Kaisar Raza
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Distt. Ajmer, Rajasthan, India 305 817
Sarwar Beg
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India 110062

ABSTRACT

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.

REFERENCES

  1. Momin M, Disouza J, Patravale V. Advances in technology and business potential of new drug delivery systems. Drug Deliv Transl Res. 2016;6(4):341.

  2. Korting S, Monika. Drug delivery. New York: Springer-Verlag; 2010.

  3. Raza K, Singh B, Singla S, Wadhwa S, Garg B, Chhibber S, Katare OP. Nanocolloidal carriers of isotretinoin: Antimicrobial activity against propionibacterium acnes and dermatokinetic modeling. Mol Pharm. 2013;10(5):1958-63.

  4. Garg NK, Tyagi RK, Singh B, Sharma G, Nirbhavane P, Kushwah V, Jain S, Katare OP. Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-KB and FOXO1. Int J Pharm. 2016;499(1-2):301-20.

  5. Singh C, Kaur R, Kaur R, Bahl R, Singh B. Multi-dimensional approaches for targeted drug delivery using nanostructured systems. In: Singh B, Kanwar JR, Garg S, editors. NanoBioEngineering. Boca Raton, FL: CRC Press; 2018. p.123-44.

  6. Nikolova M, Slavchov R, Nikolova G. Nanotechnology in medicine. In: Hock FJ, Gralinski MR, editors. Drug discovery and evaluation: Methods in clinical pharmacology. Berlin, Germany: Springer; 2018. p. 1-14.

  7. Cheng R, Meng F, Deng C, Zhong Z. Bioresponsive polymeric nanotherapeutics for targeted cancer chemotherapy. Nano Today. 2015;10(5):656-70.

  8. Crommelin DJA, Storm G, Jiskoot W, Stenekes R, Mastrobattista E, Hennink WE. Nanotechnological approaches for the delivery of macromolecules. J Control Release. 2003;87:81-8.

  9. Danhier F, Preat V, Langer R, Anderson DG. Nanoparticle-based drug delivery systems: A commercial and regulatory outlook as the field matures. Expert Opin Drug Deliv. 2017;14(7):851-64.

  10. Transparency Market Research. Global nanomedicine market to rise with increasing incidence of chronic diseases. 2018 [cited 2019 April 13]. Available from: https://www.transparencymarket- research.com/pressrelease/nanomedicine-market.htm.

  11. De Crozals G, Bonnet R, Farre C, Chaix C. Nanoparticles with multiple properties for biomedical applications: A strategic guide. Nano Today. 2016;11(4):435-63.

  12. Prud'homme RK, Svenson S. Introduction: Benefits and challenges for multifunctional nanoparticles in medicine. In: Svenson S, Prud'homme RK, editors. Multifunctional nanoparticles for drug delivery applications: Berlin, Germany: Springer; 2012. p. 1-5.

  13. Singh B, Bhatowa R, Tripathi CB, Kapil R. Developing micro-/nanoparticulate drug delivery systems using "design of experiments". Int J Pharm Investig. 2011;1(2):75-87.

  14. Aksu B, Beg S, Garg B, Kapil R, Singh B. Quality by design (QbD) in the development of nanostructured drug delivery systems. In: Singh B, Vyas SP, Kaur IP, editors. NanoBioMedicine. Houston, Texas, USA: Studium Press LLC; 2015. p. 1-30.

  15. Singh B, Kumar R, Ahuja N. Optimizing drug delivery systems using systematic "design of experiments." Part I: Fundamental aspects. Crit Rev Ther Drug Carrier Syst. 2005;22(1):27-105.

  16. Lewis GA, Mathieu D, Phan-Tan-Luu R. Pharmaceutical experimental design. Boca Raton, FL: CRC Press; 1998.

  17. Singh B, Saini S, Lohan S, Beg S. Systematic development of nanocarriers employing quality by design paradigms. In: Mishra V, Kesharwani P, Mohd Amin MCI, Iyer A, editors. Nanotechnology- based approaches for targeting and delivery of drugs and genes. New York: Academic Press; 2017. p. 110-48.

  18. Singh B, Dahiya M, Saharan V, Ahuja N. Optimizing drug delivery systems using systematic "design of experiments." Part II: Retrospect and prospects. Crit Rev Ther Drug Carrier Syst. 2005;22(3):215-94.

  19. Montgomery DC. Design and analysis of experiments. New York: Wiley; 2001.

  20. Durakovic B. Design of experiments application, concepts, examples: State of the art. PEN. 2017; 5(3):421-39.

  21. Cochran WC, Cox GM. Experimental Design. New York: Wiley; 1992.

  22. ICH. Harmonised tripartite guideline. Pharmaceutical development Q8 (R2). 2009 [cited 2019 May 10]. Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/ Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf.

  23. Singh B. Quality by design (QbD) for holistic pharma excellence and regulatory compliance. Pharma Times. 2014:26-33.

  24. Singh B, Raza K, Beg S. Developing "optimized" drug products employing "designed" experiments. Chemical Industry Digest. 2013(12):70-6.

  25. Beg S, Rahman M, Kohli K. Quality-by-design approach as a systematic tool for the development of nanopharmaceutical products. Drug Discov Today. 2019;24(3):717-25.

  26. ICH. Harmonised tripartite guideline. Quality risk management Q9 2005 [cited 2019 June 29]. Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/ Q9/Step4/Q9_Guideline.pdf.

  27. Djuris J, Djuric Z. Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment. Int J Pharm. 2017;533(2):346-56.

  28. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771-83.

  29. ICH Q14. Analytical procedure development and revision of Q2(R1) analytical validation. 2018 [cited 2019 April 16]. Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/ Guidelines/Quality/Q2_Q14/Q2R2Q14EWG_ConceptPaper_2018_1115.pdf.

  30. ICH. Harmonised tripartite guideline. ICH Q13 on Conti Manufacturing and ICH Q14 on AQbD. 2018 [cited 2019 April 14]. Available from: https://www.gmp-compliance.org/gmp-news/ new-ich-guidelines-ich-q13-on-conti-manufacturing-and-ich-q14-on-aqbd.

  31. Singh B, Kapil R, Nandi M, Ahuja N. Developing oral drug delivery systems using formulation by design: Vital precepts, retrospect and prospects. Expert Opin Drug Deliv. 2011;8(10):1341-60.

  32. Beg S, Katare OP, Singh B. Formulation by design approach for development of ultrafine self-nanoemulsifying systems of rosuvastatin calcium containing long-chain lipophiles for hyperlipidemia management. Colloids Surf B Biointerfaces. 2017;159:869-79.

  33. Singh B. Evolution of a revolution: An autobiographical account on formulation by design. Pharma Rev. 2013:36-42.

  34. Beg S, Akhter S, Rahman M, Rahman Z. Perspectives of quality by design approach in nanomedicines development. Curr Nanomed. 2017;7(3):191-97.

  35. Singh B, Garg B, Chaturvedi SC, Arora S, Mandsaurwale R, Kapil R, Singh B. Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends. J Pharm Pharmacol. 2012;64(5):654-69.

  36. Singh B, Pahuja S, Kapil R, Ahuja N. Formulation development of oral controlled release tablets of hydralazine: Optimization of drug release and bioadhesive characteristics. Acta Pharm. 2009;59(1):1-13.

  37. Beg S, Sharma G, Katare OP, Lohan S, Singh B. Development and validation of a stability-indicating liquid chromatographic method for estimating olmesartan medoxomil using quality by design. J Chromatogr Sci. 2015;53(7):1048-59.

  38. Akesolo U, Maguregui MI, Gonzalez L, Jimenez RM, Alonso RM. Experimental design optimization of a capillary zone electrophoresis method for the screening of several diuretics and ACE inhibitors. J Chromatogr Sci. 2004;42(2):74-9.

  39. Armstron NA, James KC. Understanding experimental design and interpretation in pharmaceutics. Dordrecht (Netherlands) Elsevier; 1991.

  40. Singh B, Mehta G, Kumar R, Bhatia A, Ahuja N, Katare OP. Design, development and optimization of nimesulide-loaded liposomal systems for topical application. Curr Drug Deliv. 2005;2(2):143-53.

  41. Schwartz JB, Connor RE. Optimization techniques in pharmaceutical formulation and processing. In: Banker GS, Rhodes CT, editors. Modern pharmaceutics. New York: Marcel Dekker; 1996.

  42. Weissman SA, Anderson NG. Design of experiments (DoE) and process optimization: A review of recent publications. Org Process Res Dev. 2015;19(11):1605-33.

  43. Bhavsar MD, Tiwari SB, Amiji MM. Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design. J Control Release. 2006;110(2):422-30.

  44. Lewis GA. Optimization methods. In: Swarbrick J, Boylan JC, editors. Encyclopedia of pharmaceutical technology. Madison, New York, USA: Marcel Dekker; 2002.

  45. Araujo PW, Brereton RG. Experimental design II. Optimization. Trends Anal Chem. 1996;15:63-70.

  46. Jog R, Unachukwu K, Burgess DJ. Formulation design space for stable, pH sensitive crystalline nife-dipine nanoparticles. Int J Pharm. 2016;514(1):81-92.

  47. Singh B, Garg B, Sandhu PS, Kaur R, Saini S. Systematic optimization of pharmaceutical products and processes using modern approaches. In: Jain NK, editor. Pharmaceutical product development. 3rd ed. India: CBS Publishers; 2018. p. 383-435.

  48. Beg S, Saini S, Bandopadhyay S, Katare O, Singh B. QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of olmesartan medoxomil employing multivariate statistical techniques. Drug Deliv Ind Pharm. 2018;44(3):407-20.

  49. Singh B, Khurana RK, Lohan S, Sandhu PS, Beg S, Anuja N. Developing optimized nanopharmaceuticals employing rational use of systematic multivariate techniques. In: Singh B, Singh KK, Rekhi GS, editors. NanoBioMedicine. Houston, Texas, USA: Studium Press LLC; 2015. p. 251-303.

  50. Houson I. Process understanding: For scale-up and manufacture of active ingredients. New York: Wiley; 2011.

  51. Katare OP, Singh B, Nirbhavane P, Kumar R. Pharmaceutical pilot-plant and scale-up in product development. In: Jain NK, editor. Pharmaceutical product development. New Delhi, India: CBS Publishers and Distributors; 2018. p. 549-95.

  52. Shah B, Khunt D, Bhatt H, Misra M, Padh H. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters. Eur J Pharm Sci. 2015;78:54-66.

  53. Singh B, Khurana RK, Garg B, Saini S, Kaur R. Stimuli-responsive systems with diverse drug delivery and biomedical applications: Recent updates and mechanistic pathways. Crit Rev Ther Drug Carrier Syst. 2017;34(3):209-55.

  54. Kanwar N, Sinha VR. In situ forming depots as sustained release drug delivery systems. Crit Rev Ther Drug Carrier Syst. 2019;36(2):93-136.

  55. Sharma R, Dubey S, Mody N, Sharma G, Kushwah V, Jain S, Katare OP, Vyas SP. Release promoter-based systematically designed nanocomposite(s): A novel approach for site-specific delivery of tumor-associated antigen(s) (TAAs). Artif Cells Nanomed Biotechnol. 2018;46:1-14.

  56. Khurana RK, Bansal AK, Beg S, Burrow AJ, Katare OP, Singh KK, Singh B. Enhancing biophar-maceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation. Int J Pharm. 2017;518(1):289-306.

  57. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, Samiei M, Kouhi M, Nejati-Koshki K. Liposome: Classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102.

  58. Rana V, Kamboj S, Sethi S. Lipid-based nanocarriers in lymphatic transport of drugs: Retrospect and prospects. In: Singh B, Ho JYR, Kanwar J, editors. NanoBioMaterials. Boca Raton, FL: CRC Press; 2018. p. 67-96.

  59. Shukla A, Singh B, Katare OP. Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano-bilosomes. Br J Pharmacol. 2011;164(2b):820-27.

  60. Garg BJ, Garg NK, Beg S, Singh B, Katare OP. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: Formulation optimization, in vitro evaluation and preclinical assessment. J Drug Target. 2016;24(3):233-46.

  61. Raza K, Singh B, Mahajan A, Negi P, Bhatia A, Katare OP. Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin. J Drug Target. 2011; 19(4):293-302.

  62. Yasir M, Sara UVS. Preparation and optimization of haloperidol loaded solid lipid nanoparticles by Box-Behnken design. J Pharm Res. 2013;7(6):551-58.

  63. Karunanidhi P, Puran Lal S, Singh S. Optimization of processing parameters for the development of Ficus religiosa L. extract loaded solid lipid nanoparticles using central composite design and evaluation of antidiabetic efficacy. J Drug Deliv Sci Technol. 2018;43:94-102.

  64. Patil H, Feng X, Ye X, Majumdar S, Repka MA. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: A systematic study based on a quality by design approach. AAPS J. 2015;17(1):194-205.

  65. Garg NK, Singh B, Jain A, Nirbhavane P, Sharma R, Tyagi RK, Kushwah V, Jain S, Katare OP. Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics. Colloids Surf B Biointerfaces. 2016;146:114-26.

  66. Sharma G, Thakur K, Raza K, Singh B, Katare OP. Nanostructured lipid carriers: A new paradigm in topical delivery for dermal and transdermal applications. Crit Rev Ther Drug Carrier Syst. 2017;34(4): 355-86.

  67. Garg NK, Sharma G, Singh B, Nirbhavane P, Tyagi RK, Shukla R, Katare OP. Quality by design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s). Int J Pharm. 2017;517(12):413-31.

  68. Singh B, Bandopadhyay S, Kapil R, Singh R, Katare OP. Self-emulsifying drug delivery systems (SEDDS): Formulation development, characterization, and applications. Crit Rev Ther Drug Carrier Syst. 2009;26(5):427-51.

  69. Talelli M, Barz M, Rijcken CJF, Kiessling F, Hennink WE, Lammers T. Core-crosslinked polymeric micelles: Principles, preparation, biomedical applications and clinical translation. Nano Today. 2015;10(1):93-17.

  70. Singh B, Beg S, Khurana RK, Sandhu PS, Kaur R, Katare OP. Recent advances in self-emulsifying drug delivery systems (SEDDS). Crit Rev Ther Drug Carrier Syst. 2014;31(2):121-85.

  71. Kaur R, Kaur R, Singh C, Kaur S, Goyal AK, Singh KK, Singh B. Inhalational drug delivery in pulmonary aspergillosis. Crit Rev Ther Drug Carrier Syst. 2019;36(3):183-217.

  72. Jain A, Jain A, Garg NK, Tyagi RK, Singh B, Katare OP, Webster TJ, Soni V. Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer. Acta Biomater. 2015;24:140-51.

  73. Jose C, Amra K, Bhavsar C, Momin M, Omri A. Polymeric lipid hybrid nanoparticles: Properties and therapeutic applications. Crit Rev Ther Drug Carrier Syst. 2018;35(6):555-88.

  74. Cun D, Jensen DK, Maltesen MJ, Bunker M, Whiteside P, Scurr D, Foged C, Nielsen HM. High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: Quality by design optimization and characterization. Eur J Pharm Biopharm. 2011;77(1):26-35.

  75. Hunter AC, Elsom J, Wibroe PP, Moghimi SM. Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective. Nanomedicine. 2012;8:S5-S20.

  76. Nagpal K, Kumar P, Mohan A, Thakur S. Dendrimers for therapeutic delivery: compositions, characterizations, and current status. Crit Rev Ther Drug Carrier Syst. 2019;36:277-304.

  77. Gajra B, Dalwadi C, Patel R. Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design. DARU J Pharm Sci. 2015;23(1):1-3.

  78. Li J, Qiao Y, Wu Z. Nanosystem trends in drug delivery using quality-by-design concept. J Control Rel. 2017;256:9-18.

  79. Sylvester B, Porfire A, Achim M, Rus L, Tomuja I. A step forward towards the development of stable freeze-dried liposomes: A quality by design approach (QbD). Drug Dev Ind Pharm. 2018;44(3):385-97.

  80. Porfire A, Muntean DM, Rus L, Sylvester B, Tomuta I. A quality by design approach for the development of lyophilized liposomes with simvastatin. Saudi Pharm J. 2017;25(7):981-92.

  81. Prasad PS, Imam SS, Aqil M, Sultana Y, Ali A. QbD-based carbopol transgel formulation: Characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes. Drug Deliv. 2016;23(3):1047-56.

  82. Negi P, Singh B, Sharma G, Beg S, Raza K, Katare OP. Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv. 2016;23(3):941-57.

  83. Yao X, Bunt C, Cornish J, Quek SY, Wen J. Preparation, optimization and characterization of bovine lactoferrin-loaded liposomes and solid lipid particles modified by hydrophilic polymers using factorial design. Chem Biol Drug Des. 2014;83(5):560-75.

  84. Xu X, Khan MA, Burgess DJ. A quality by design (QbD) case study on liposomes containing hydrophilic API: Screening of critical variables, and establishment of design space at laboratory scale. Int J Pharm. 2012;423(2):543-53.

  85. Mura P, Capasso G, Maestrelli F, Furlanetto S. Optimization of formulation variables of benzocaine liposomes using experimental design. J Liposome Res. 2008;18(2):113-25.

  86. Xia F, Jin H, Zhao Y, Guo X. Preparation of coenzyme Q10 liposomes using supercritical anti-solvent technique. J Microencap. 2012;29(1):21-9.

  87. Chauhan MK, Bhatt N. Bioavailability enhancement of polymyxin B with novel drug delivery: Development and optimization using quality-by-design approach. J Pharm Sci. 2019;108:1521-28.

  88. Abdelbary AA, AbouGhaly MHH. Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: Application of Box-Behnken design, in-vitro evaluation and in-vivo skin deposition study. Int J Pharm. 2015;485(1):235-43.

  89. Gonzalez-Rodriguez ML, Mouram I, Cozar-Bernal MJ, Villasmil S, Rabasco AM. Applying the Taguchi method to optimize sumatriptan succinate niosomes as drug carriers for skin delivery. J Pharm Sci. 2012;101(10):3845-63.

  90. Moolakkadath T, Aqil M, Ahad A, Imam SS, Iqbal B, Sultana Y, Mujeeb M, Iqbal Z. Development of transethosomes formulation for dermal fisetin delivery: Box-Behnken design, optimization, in vitro skin penetration, vesicles-skin interaction and dermatokinetic studies. Artif Cells Nanomed Biotechnol. 2018;46:1-11.

  91. Ahmed S, Sarim Imam S, Zafar A, Ali A, Aqil M, Gull A. In vitro and preclinical assessment of factorial design based nanoethosomes transgel formulation of an opioid analgesic. Artif Cells Nanomed Biotechnol. 2016;44(8):1793-802.

  92. Jain S, Patel N, Madan P, Lin S. Quality by design approach for formulation, evaluation and statistical optimization of diclofenac-loaded ethosomes via transdermal route. Pharm Dev Technol. 2015;20(4):473-89.

  93. Pitta SK, Dudhipala N, Narala A, Veerabrahma K. Development of zolmitriptan transfersomes by Box-Behnken design for nasal delivery: In vitro and in vivo evaluation. Drug Deliv Ind Pharm. 2018;44(3):484-92.

  94. Das B, Sen SO, Maji R, Nayak AK, Sen KK. Transferosomal gel for transdermal delivery of risperidone: Formulation optimization and ex vivo permeation. J Drug Deliv Sci Technol. 2017; 38:59-71.

  95. Ahmed TA. Preparation of transfersomes encapsulating sildenafil aimed for transdermal drug delivery: Plackett-Burman design and characterization. J Liposome Res. 2015;25(1):1-10.

  96. Khalil RM, Abdelbary A, Kocova El-Arini S, Basha M, El-Hashemy HA. Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization. J Liposome Res. 2018;29(2):1-12.

  97. Al-mahallawi AM, Abdelbary AA, Aburahma MH. Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam. Int J Pharm. 2015;485(1):329-40.

  98. Aziz DE, Abdelbary AA, Elassasy AI. Fabrication of novel elastosomes for boosting the transdermal delivery of diacerein: Statistical optimization, ex-vivo permeation, in-vivo skin deposition and pharmacokinetic assessment compared to oral formulation. Drug Deliv. 2018;25(1):815-26.

  99. El-Say KM, Hosny KM. Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits. PLoS One. 2018;13(8):1-15.

  100. Beg S, Jain S, Kushwah V, Bhatti GK, Sandhu PS, Katare O, Singh B. Novel surface-engineered solid lipid nanoparticles of rosuvastatin calcium for low-density lipoprotein-receptor targeting: A quality by design-driven perspective. Nanomedicine. 2017;12(4):333-56.

  101. Kumar P, Sharma G, Kumar R, Malik R, Singh B, Katare OP, Raza K. Stearic acid based, systematically designed oral lipid nanoparticles for enhanced brain delivery of dimethyl fumarate. Nanomedicine. 2017;12(23):2607-21.

  102. Behbahani ES, Ghaedi M, Abbaspour M, Rostamizadeh K. Optimization and characterization of ultrasound assisted preparation of curcumin-loaded solid lipid nanoparticles: Application of central composite design, thermal analysis and X-ray diffraction techniques. Ultrason Sonochem. 2017;38:271-80.

  103. Kauffman KJ, Dorkin J, Yang JH, Heartlein MW, DeRosa F, Mir FF, Fenton OS, Anderson DG. Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs. Nano Lett. 2015;15(11):7300-06.

  104. Raza K, Singh B, Singal P, Wadhwa S, Katare OP. Systematically optimized biocompatible isotretinoin-loaded solid lipid nanoparticles (SLNs) for topical treatment of acne. Colloids Surf B Biointerfaces. 2013;105:67-74.

  105. Zhang C, Gu C, Peng F, Liu W, Wan J, Xu H, Lam CW, Yang X. Preparation and optimization of triptolide-loaded solid lipid nanoparticles for oral delivery with reduced gastric irritation. Molecules. 2013;18(11):13340-56.

  106. Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, Peng X. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomed. 2011;6:683-92.

  107. Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol. 2011;63(3):342-51.

  108. Varshosaz J, Tabbakhian M, Mohammadi MY. Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability. J Liposome Res. 2010;20(4):286-96.

  109. Shah M, Pathak K. Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 23 full-factorial design. AAPS PharmSciTech. 2010;11(2):489-96.

  110. Alam T, Khan S, Gaba B, Haider MF, Baboota S, Ali J. Quality by design based development of isradipine nanostructured lipid carrier and its evaluation for in vitro gut permeation and in vivo solubilisation fate. J Pharm Sci. 2018;517:1-46.

  111. Thapa C, Ahad A, Aqil M. Formulation and optimization of nanostructured lipid carriers to enhance oral bioavailability of telmisartan using Box-Behnken design. J Drug Deliv Sci Technol. 2018;44:431-39.

  112. Kudarha R, Dhas NL, Pandey A, Belgamwar VS, Ige PP. Box-Behnken study design for optimization of bicalutamide-loaded nanostructured lipid carrier: Stability assessment. Pharm Dev Technol. 2015;20(5):608-18.

  113. Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB. Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids Surf B Biointerfaces. 2010;81(2):412-21.

  114. Garg B, Beg S, Kaur R, Kumar R, Katare OP, Singh B. Long-chain triglycerides-based self-nanoemul-sifying oily formulations (SNEOFs) of darunavir with improved lymphatic targeting potential. J Drug Target. 2018;26(3):252-66.

  115. Singh B, Khurana L, Bandyopadhyay S, Kapil R, Katare OP. Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential. Drug Deliv. 2011;18(8):599-12.

  116. Bandyopadhyay S, Beg S, Katare OP, Sharma G, Singh B. QbD-oriented development of self-nano-emulsifying drug delivery systems (SNEDDS) of valsartan with improved biopharmaceutical performance. Curr Drug Deliv. 2015;12(5):544-63.

  117. Kassem AM, Ibrahim HM, Samy AM. Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: In vitro and in vivo evaluation. J Microencap. 2017;34(3):319-33.

  118. Tripathi CB, Beg S, Kaur R, Shukla G, Bandopadhyay S, Singh B. Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential. Drug Deliv. 2016;23(9):3209-23.

  119. Garg B, Katare OP, Beg S, Lohan S, Singh B. Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir. Colloids Surf B Biointerfaces. 2016;141:611-22.

  120. Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces. 2012;100:50-61.

  121. Garg V, Kaur P, Singh SK, Kumar B, Bawa P, Gulati M, Yadav AK. Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation. Eur J Pharm Biopharm. 2017;109:297-315.

  122. Beg S, Sandhu PS, Batra RS, Khurana RK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Deliv. 2015;22(6):765-84.

  123. Beg S, Swain S, Singh HP, Patra C, Rao MEB. Development, optimization, and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers. AAPS PharmSciTech. 2012;13(4):1416-27.

  124. Jain A, Kaur R, Beg S, Kushwah V, Jain S, Singh B. Novel cationic supersaturable nanomicellar systems of raloxifene hydrochloride with enhanced biopharmaceutical attributes. Drug Deliv Transl Res. 2018;8(3):670-92.

  125. Beg S, Sharma G, Thanki K, Jain S, Katare OP, Singh B. Positively charged self-nanoemulsifying oily formulations of olmesartan medoxomil: Systematic development, in vitro, ex vivo and in vivo evaluation. Int J Pharm. 2015;493(1):466-82.

  126. Sharma G, Beg S, Thanki K, Katare OP, Jain S, Kohli K, Singh B. Systematic development of novel cationic self-nanoemulsifying drug delivery systems of candesartan cilexetil with enhanced biopharmaceutical performance. RSC Adv. 2015;5(87):71500-13.

  127. Chavan RB, Modi SR, Bansal AK. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. Int J Pharm. 2015;495(1):374-84.

  128. Singh G, Pai RS. Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: Optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies. Drug Deliv. 2015;22(4):522-30.

  129. Ozdemir S, Qelik B, Turkoz Acar E, Duman G, Uner M. Eplerenone nanoemulsions for treatment of hypertension. Part I: Experimental design for optimization of formulations and physical characterization. J Drug Deliv Sci Technol. 2018;45:357-66.

  130. Argenta DF, de Mattos CB, Misturini FD, Koester LS, Bassani VL, Simoes CO, Teixeira HF. Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein. Int J Nanomed. 2014;9:4737-47.

  131. Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces. 2014; 113:330-37.

  132. Dordevic SM, Radulovic TS, Cekic ND, Randelovic DV, Savic MM, Krajisnik DR, Milic JR, Savic SD. Experimental design in formulation of diazepam nanoemulsions: Physicochemical and pharmacokinetic performances. J Pharm Sci. 2013;102(11):4159-72.

  133. Maher PG, Fenelon MA, Zhou Y, Kamrul Haque M, Roos YH. Optimization of P-Casein stabilized nanoemulsions using experimental mixture design. J Food Sci. 2011;76(8):1108-17.

  134. Attari Z, Kalvakuntla S, Reddy MS, Deshpande M, Rao CM, Koteshwara KB. Formulation and characterisation of nanosuspensions of BCS class II and IV drugs by combinative method. J Exp Nanosci. 2016;11(4):276-88.

  135. Karakucuk A, Celebi N, Teksin ZS. Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A design of experiment approach. Eur J Pharm Biopharm. 2016;95:111-21.

  136. Verma S, Lan Y, Gokhale R, Burgess DJ. Quality by design approach to understand the process of nanosuspension preparation. Int J Pharm. 2009;377(1-2):185-98.

  137. Adebileje T, Adebileje S, Aye PO. Ciprofloxacin hydrochloride encapsulated into PLGA nanoparticles for drug delivery application: Fractional factorial design. OA Lib J. 2018;5(2):1-14.

  138. Chaves LL, Costa LSA, Vieira AC, Barreiros L, Segundo MA, Ferreira D, Sarmento B, Reis S. pH-sensitive nanoparticles for improved oral delivery of dapsone: risk assessment, design, optimization and characterization. Nanomedicine. 2017;12(16):1975-90.

  139. Kasinathan N, Amirthalingam M, Reddy ND, Jagani HV, Volety SM, Rao JV In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments. Drug Deliv. 2016;23(3):1007-15.

  140. Dizaj SM, Lotfipour F, Barzegar-Jalali M, Zarrintan MH, Adibkia K. Box-Behnken experimental design for preparation and optimization of ciprofloxacin hydrochloride-loaded CaCO3 nanoparticles. J Drug Deliv Sci Technol. 2015;29:125-31.

  141. Singh G, Pai RS. Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential. Expert Opin Drug Deliv. 2014;11(5):647-59.

  142. Kharia AA, Singhai AK. Screening of most effective variables for development of gastroretentive mucoadhesive nanoparticles by Taguchi design. ISRN Nanomaterials. 2013;2013:1-8.

  143. Park SJ, Choo GH, Hwang SJ, Kim MS. Quality by design: screening of critical variables and formulation optimization of Eudragit E nanoparticles containing dutasteride. Arch Pharm Res. 2013;36(5):593-601.

  144. Yerlikaya F, Ozgen A, Vural I, Guven O, Karaagaoglu E, Khan MA, Capan Y. Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. J Pharm Sci. 2013;102(10):3748-61.

  145. Gazori T, Khoshayand MR, Azizi E, Yazdizade P, Nomani A, Haririan I. Evaluation of alginate/chitosan nanoparticles as antisense delivery vector: formulation, optimization and in vitro characterization. Carbohydr Polym. 2009;77(3):599-606.

  146. Shamekhi F, Tamjid E, Khajeh K. Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients. Int J Biol Macromol. 2018;120:460-67.

  147. Garala KC, Shinde AJ, More HN. Solubility enhancement of aceclofenac using dendrimer. Res J Pharm Dosage Forms Technol. 2009;1(2):94-6.

  148. Zarandi MA, Zahedi P, Rezaeian I, Salehpour A, Gholami M, Motealleh B. Drug release, cell adhesion and wound healing evaluations of electrospun carboxymethyl chitosan/polyethylene oxide nanofibres containing phenytoin sodium and vitamin C. IET Nanobiotechnol. 2015;9(4):191-200.

  149. Nadia AA, Leila R, Mohammad I, Ismaeil H. Fabrication of PLA/PEG/MWCNT electrospun nanofibrous scaffolds for anticancer drug delivery. J Appl Polym Sci. 2015;132(3):1-9.

  150. Asfaram A, Ghaedi M, Purkait K. Novel synthesis of nanocomposite for the extraction of sildenafil citrate (Viagra) from water and urine samples: Process screening and optimization. Ultrason Sonochem. 2017;38:463-72.

  151. Dadkhah D, Navarchian AH, Aref L, Tavakoli N. Application of Taguchi method to investigate the drug release behavior of poly(acrylamide-co-maleic acid)/montmorillonite nanocomposite hydrogels. Adv Polym Tech. 2014;33(4):1-9.

  152. Nadaf SJ, Killedar SG. Curcumin nanocochleates: Use of design of experiments, solid state characterization, in vitro apoptosis and cytotoxicity against breast cancer MCF-7 cells. J Drug Deliv Sci Technol. 2018;47:337-50.

  153. Raviadaran R, Chandran D, Shin LH, Manickam S. Optimization of palm oil in water nano-emulsion with curcumin using microfluidizer and response surface methodology. LWT. 2018;96:58-65.

  154. Avasatthi V, Pawar H, Dora CP, Bansod P, Gill MS, Suresh S. A novel nanogel formulation of methotrexate for topical treatment of psoriasis: Optimization, in vitro and in vivo evaluation. Pharm Dev Technol. 2016;21(5):554-62.

  155. Water JJ, Kim YT, Maltesen MJ, Franzyk H, Foged C, Nielsen HM. Hyaluronic acid-based nanogels produced by microfluidics-facilitated self-assembly improves the safety profile of the cationic host defense peptide novicidin. Pharm Res. 2015;32(8):2727-35.

  156. Ishak RAH, Mostafa NM, Kamel AO. Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain delivery-comparative study with the gold standard (Tween 80): Optimization, characterization and biodistribution. Drug Deliv. 2017;24(1):1874-90.

  157. Yalcin TE, Ilbasmis-Tamer S, Takka S. Development and characterization of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs) using central composite design. Int J Pharm. 2018;548(1):255-62.

  158. Dave V, Yadav RB, Kushwaha K, Yadav S, Sharma S, Agrawal U. Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system. Bioact Mater. 2017;2(4):269-80.

  159. Sengel-Turk CT, Hascicek C. Design of lipid-polymer hybrid nanoparticles for therapy of BPH: Part I. Formulation optimization using a design of experiment approach. J Drug Deliv Sci Technol. 2017;39:16-27.

  160. Tahir N, Madni A, Balasubramanian V, Rehman M, Correia A, Kashif PM, Makila E, Salonen J, Santos HA. Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications. Int J Pharm. 2017;533(1):156-68.

  161. Rose F, Wern JE, Ingvarsson PT, van de Weert M, Andersen P, Follmann F, Foged C. Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach. J Control Rel. 2015;210:48-57.

  162. Junghanns J, Muller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed. 2008;3(3):295-309.

  163. Boles MA, Ling D, Hyeon T, Talapin DV. The surface science of nanocrystals. Nat Mater. 2016;15:141.

  164. Leopold L, Zhao C, McConnachie L, Khurana RK, Sharma T, Singh B, Ho RJY. Surface engineered nanomaterial: Environmental and safety considerations in pharmaceutical and medicinal products. In: Singh B, Kanwar JR, Garg S, editors. NanoBioEngineering. Boca Raton, FL: CRC Press; 2018. p. 297-310.

  165. Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. J Pharm Bioallied Sci. 2010;2(4):282-89.

  166. Baughman RH, Zakhidov AA, De Heer WA. Carbon nanotubes-the route toward applications. Science. 2002;297(5582):787-92.

  167. Sun YP, Fu K, Lin Y, Huang W. Functionalized carbon nanotubes: properties and applications. Acc Chem Res. 2002;35(12):1096-104.

  168. Bera D, Qian L, Tseng T-K, Holloway PH. Quantum dots and their multimodal applications: A review. Materials. 2010;3(4):2260-345.

  169. Tripathi S, Kaur G, Khurana RK, Kapoor S, Singh B. Quantum dots and their potential role in cancer theranostics. Crit Rev Ther Drug Carrier Syst. 2015;32(6):461-502.

  170. Sathigari SK, Ober CA, Sanganwar GP, Gupta RB, Babu RJ. Single-step preparation and deagglomeration of itraconazole microflakes by supercritical antisolvent method for dissolution enhancement. J Pharm Sci. 2011;100(7):2952-65.

  171. Chopra D, Gupta KC, Sharma S, Katri M, Singh B, Singh B. Nanostructured drug delivery: Toxicological challenges and safety issues. In: Singh B, Kanwar JR, Katare OP, editors. NanoMedicine. Houston, Texas, USA: Studium Press LLC; 2015. p. 493-535.

  172. Alshweiat A, Katona G, Csoka I, Ambrus R. Design and characterization of loratadine nanosuspension prepared by ultrasonic-assisted precipitation. Eur J Pharm Sci. 2018;122:94-104.

  173. Alshweiat A, Ambrus R, Katona G, Csoka I. QbD based control strategy of loratadine nanosuspensions and dry nanoparticles stabilized by soluplus. Farmacia. 2019;67:729-35.

  174. Pallagi E, Ambrus R, Szabo-Revesz P, Csoka I. Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation. Int J Pharm. 2015; 491(1-2):384-92.

  175. Ismail R, Sovany T, Gacsi A, Ambrus R, Katona G, Imre N, Csoka I. Synthesis and statistical optimization of poly (lactic-co-glycolic acid) nanoparticles encapsulating GLP1 analog designed for oral delivery. Pharm Res. 2019;36(7):99.

  176. Chung N-O, Lee MK, Lee J. Mechanism of freeze-drying drug nanosuspensions. Int J Pharm. 2012;437(1-2):42-50.

  177. Niu L, Panyam J. Freeze concentration-induced PLGA and polystyrene nanoparticle aggregation: Imaging and rational design of lyoprotection. J Control Release. 2017;248:125-32.

  178. Gajera BY, Shah DA, Dave RH. Investigating a novel hot melt extrusion-based drying technique to solidify an amorphous nanosuspension using design of experiment methodology. AAPS PharmSciTech. 2018;19(8):3778-90.

  179. Kassem MAA, ElMeshad AN, Fares AR. Enhanced solubility and dissolution rate of lacidipine nano-suspension: Formulation via antisolvent sonoprecipitation technique and optimization using Box-Behnken design. AAPS PharmSciTech. 2017;18(4):983-96.

  180. Hao J, Gao Y, Zhao J, Zhang J, Li Q, Zhao Z, Liu J. Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design. AAPS PharmSciTech. 2014;16(1):118-28.

  181. Kumar S, Gokhale R, Burgess DJ. Quality by design approach to spray drying processing of crystalline nanosuspensions. Int J Pharm. 2014;464(1):234-42.

  182. Nakarani M, Misra AK, Patel JK, Vaghani SS. Itraconazole nanosuspension for oral delivery: Formulation, characterization and in vitro comparison with marketed formulation. Daru. 2010;18(2):84-90.

  183. Yiamsawas D, Boonpavanitchakul K, Kangwansupamonkon W. Optimization of experimental parameters based on the Taguchi robust design for the formation of zinc oxide nanocrystals by solvothermal method. Mater Res Bull. 2011;46(5):639-42.

  184. Yue PF, Li Y, Wan J, Wang Y, Yang M, Zhu WF, Wang CH, Yuan H. Process optimization and evaluation of novel baicalin solid nanocrystals. Int J Nanomed. 2013;8:2961-73.

  185. Koradia DK, Parikh HR. Dissolution enhancement of albendazole through nanocrystal formulation. J Pharm Bioallied Sci. 2012;4(1):62-3.

  186. Shah S, Parmar B, Soniwala M, Chavda J. Design, optimization, and evaluation of lurasidone hydrochloride nanocrystals. AAPS PharmSciTech. 2016;17:1150-58.

  187. Adena SKR, Upadhyay M, Vardhan H, Mishra B. Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design. Drug Deliv Ind Pharm. 2018;44(3):493-501.

  188. Lohan S, Raza K, Mehta SK, Bhatti GK, Saini S, Singh B. Anti-Alzheimer's potential of berberine using surface decorated multi-walled carbon nanotubes: A preclinical evidence. Int J Pharm. 2017;530(1):263-78.

  189. Farahani BV, Behbahani R, Javadi N. Functionalized multi walled carbon nanotubes as a carrier for doxorubicin: Drug adsorption study and statistical optimization of drug loading by factorial design methodology. J Braz Chem Soc. 2016;27(4):694-05.

  190. Nemati F, Zare-Dorabei R, Hosseini M, Ganjali MR. Fluorescence turn-on sensing of thiamine based on arginine-functionalized graphene quantum dots (Arg-GQDs): Central composite design for process optimization. Sens Actuators B. 2018;255:2078-85.

  191. Peltonen L. Design space and QbD approach for production of drug nanocrystals by wet media milling techniques. Pharmaceutics. 2018;10(3):104-8.

  192. Sanganwar GP, Sathigari S, Babu RJ, Gupta RB. Simultaneous production and co-mixing of microparticles of nevirapine with excipients by supercritical antisolvent method for dissolution enhancement. Eur J Pharm Sci. 2010;39(1-3):164-74.

  193. Ghosh I, Schenck D, Bose S, Liu F, Motto M. Identification of critical process parameters and its interplay with nanosuspension formulation prepared by top down media milling technology-a QbD perspective. Pharm Dev Technol. 2013;18(3):719-29.

  194. Kumar N, Chaurasia S, Patel RR, Kumar V, Mishra B. Development and optimization of atorvastatin calcium loaded oral biodegradable polymeric nanoparticles using central composite design. Adv Sci Lett. 2014;20(5-6):984-93.

  195. Iranajan M. Formulation by design: An approach to designing better drug delivery systems. Pharma Times. 2018:9-14.

  196. Basheer IA, Hajmeer M. Artificial neural networks: Fundamentals, computing, design, and application. J Microbiol Methods. 2000;43(1):3-31.

  197. Singh B, Khatri M, Nanda S. Regulating nanomedicines: Need for paradigm shift. Chronicle PharmaBiz. 2014;14:44-6.

  198. Nanda S, Nanda A, Singh B. Federal perspectives of nanostructured systems: An update. In: Singh B, Vyas SP, Kaur IP, editors. Nanostructured Drug Delivery. Houston, Texas, USA: Studium Press LLC; 2015. p. 491-525.

  199. Re F, Gregori M, Masserini M. Nanotechnology for neurodegenerative disorders. Nanomedicine. 2012;8:S51-S8.

  200. Arora S, Rajwade JM, Paknikar KM. Nanotoxicology and in vitro studies: The need of the hour. Toxicol Appl Pharmacol. 2012;258(2):151-65.

  201. Wang J, Asbach C, Fissan H, Hulser T, Kuhlbusch TA, Thompson D, Pui DY. How can nanobiotechnology oversight advance science and industry: examples from environmental, health, and safety studies of nanoparticles (nano-EHS). J Nanopart Res. 2011;13(4):1373-87.

  202. Keck CM, Muller RH. Nanotoxicological classification system (NCS)-a guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur J Pharm Biopharm. 2013;84(3):445-8.

  203. FDA. Drug products, including biological products, that contain nanomaterials. 2017 [cited 2019 April 16]. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM588857.pdf.

  204. Ganguly P, Breen A, Pillai SC. Toxicity of nanomaterials: Exposure, pathways, assessment, and recent advances. ACS Biomater Sci Eng. 2018;4(7):2237-75.

  205. Sharifi S, Behzadi S, Laurent S, Forrest ML, Stroeve P, Mahmoudi M. Toxicity of nanomaterials. Chem Soc Rev. 2012;41(6):2323-43.

  206. Nanda S, Nanda A, Singh B. Federal perspectives of nanostructured systems: An update. In: Singh B, Vyas S, Kaur I, editors. NanoStructured Drug Delivery. Houston, Texas: Studium Press LLC; 2015. p. 491-527.

  207. European Medicines Agency. Quality aspects of nano-based medicines. 2014 [cited 2019 April 14]. Available from: https://www.ema.europa.eu/en/documents/presentation/presentation-quality-aspects-nano-based-medicines-dolores-hernan-pacrez-de-la-ossa_en.pdf.

  208. European Medicines Agency. Data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. 2014 [cited 2019 April 19]. Available from: https://www. ema.europa.eu/en/data-requirements-intravenous-liposomal-products-developed-reference-innovator-liposomal-product-0.

  209. European Medicines Agency. Surface coatings: General issues for consideration regarding parenteral administration of coated nanomedicine products. 2013 [cited 2019 April 14]. Available from: https:// www.ema.europa.eu/en/surface-coatings-general-issues-consideration-regarding-parenteral-adminis-tration-coated.

  210. European Medicines Agency. Development of block-copolymer-micelle medicinal products. 2014 [cited 2019 April 19]. Available from: https://www.ema.europa.eu/en/development-block-copolymer-micelle-medicinal-products.

  211. European Medicines Agency. Data requirements for intravenous iron-based nano-colloidal products developed with reference to an innovator medicinal product. 2015 [cited 2019 April 22]. Available from: https://www.ema.europa.eu/en/data-requirements-intravenous-iron-based-nano-colloidal-products-de-veloped-reference-innovator.

  212. Department of Biotechnology Indian Society of Nanomedicine. Guidelines for evaluation of nano-pharmaceuticals in India. 2019 [cited 2019 March 29]. Available from: http://www.dbtindia.nic.in/wp-content/uploads/Modified-Guidelines-for-Evaluation-of-Nanopharmaceuticals-in-India-converted-2. pdf.

  213. Therapeutic Goods Administration Australia. Regulation of nanomedicines 2016 [cited 2019 April 23]. Available from: https://www.tga.gov.au/sites/default/files/tga-presentation-nanoparticle-thera-peutics-2016-20-october-2016.pdf.

  214. Health Canada. Quality (chemistry and manufacturing) guidance: new drug submissions (ndss) and abbreviated new drug submissions (ANDSs) 2017 [cited 2019 April 19]. Available from: https://www. canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/drug-products/applications- submissions/guidance-documents/chemical-entity-products-quality/guidance-document-quality-chemistry-manufacturing-guidance-new-drug-submissions-ndss-abbreviated-new-drug-submissions. pdf.

  215. Ministry of Health, Labor, and Welfare Japan. Guideline for the development of liposome drug products. 2016 [cited 2019 April 24]. Available from: http://www.nihs.go.jp/drug/section4/160328_ MHLW_liposome_guideline.pdf.

  216. Centre for Drug Evaluation Taiwan. Regulatory considerations for nanotechnology-related drug products in Taiwan. 2017 [cited 2019 June 23]. Available from: https://www.pmda.go.jp/files/000151972. pdf.

  217. ECA Foundation. New FDA guidance on liposomes. 2019 [cited 2019 March 19]. Available from: https://www.gmp-compliance.org/gmp-news/new-fda-guidance-on-liposomes.

  218. Keck CM, Muller RH. Nanotoxicological classification system (NCS)-A guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur J Pharm Biopharm. 2013;84(3):445-48.

  219. ICH. Harmonised tripartite guideline. Pharmaceutical quality system Q10 2008 [cited 2019 May 9]. Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf.


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