Skip to content
2000
image of Transformative Paths: Preclinical Drug Formulation and Delivery Approaches in Development

Abstract

This comprehensive review explores the multifaceted landscape of preclinical drug development, encompassing crucial stages, regulatory intricacies, Investigational New Drug (IND) submissions, and innovative formulation strategies. Delving into preclinical studies, the review underscores the importance of pharmacokinetics, pharmacodynamics, and safety assessments in animal models. Regulatory requirements governing preclinical studies are dissected, emphasizing compliance with global health authorities. The article provides a detailed examination of the IND submission process, elucidating essential components and documentation required for regulatory approval that are pivotal for advancing to clinical trials. Additionally, the evolving realm of Preformulation strategies is scrutinized, highlighting new methods like nanotechnology, solid dispersions, and formulas based on cyclodextrin to enhance drug solubility, stability, and bioavailability. This comprehensive overview aims to guide researchers, pharmaceutical professionals, and regulatory specialists through the complexities of preclinical development, offering insights into the latest formulation advancements from a legal point of view, making it be easy for potential drugs to go from lab to patient's bedside.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/rrct/10.2174/0115748871340281250331180316
2025-04-25
2025-10-10

  • From This Site

    /content/journals/rrct/10.2174/0115748871340281250331180316
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Rogge M.C. Taft D.R. The scope of preclinical drug development: An introduction and framework. Preclinical Drug Development. Swarbrick J. Boca Raton Taylor and Francis Group 2005 1 6 10.1201/9780849360237.ch1
    [Google Scholar]
  2. Parkinson C. Grasso P. The use of the dog in toxicity tests on pharmaceutical compounds. Hum. Exp. Toxicol. 1993 12 2 99 109 10.1177/096032719301200202 8096722
    [Google Scholar]
  3. Vos J.G. Immunotoxicity assessment: Screening and function studies. Arch. Toxicol. Suppl. 1980 4 95 108 10.1007/978‑3‑642‑67729‑8_25 7002113
    [Google Scholar]
  4. Penta J.S. Rozencweig M. Guarino A.M. Muggia F.M. Mouse and large-animal toxicology studies of twelve antitumor agents: Relevance to starting dose for Phase I clinical trials. Cancer Chemother. Pharmacol. 1979 3 2 97 101 10.1007/BF00254979 116778
    [Google Scholar]
  5. Maas J. Kamm W. Hauck G. An integrated early formulation strategy – From hit evaluation to preclinical candidate profiling. Eur. J. Pharm. Biopharm. 2007 66 1 1 10 10.1016/j.ejpb.2006.09.011 17123801
    [Google Scholar]
  6. Baldrick P. Toxicokinetics in preclinical evaluation. Drug Discov. Today 2003 8 3 127 133 10.1016/S1359‑6446(02)02568‑0 12568782
    [Google Scholar]
  7. Branch SK. Guidelines from the international conference on harmonis ation (ICH). Journal of pharmaceutical and biomedical analysis. 2005 38 5 798 8
    [Google Scholar]
  8. Requirements and guidelines for permission to import and/or manufacture of new drugs for sale or to undertake clinical trials. 2013 Available from: https://www.jli.edu.in/blog/wp-content/uploads/2017/01/Drugs-and-Cosmetics-Act-and-Rules2016.pdf
  9. OECD guideline for the testing of chemicals. 2012 Available from: https://www.oecd.org/content/dam/oecd/en/topics/policy-sub-issues/testing-of-chemicals/previous-test-guidelines/section-4/deleted-test-guidelines/deleted-test-guideline-457-2012.pdf
  10. Parija S.C. Mandal J. Ethics of involving animals in research. Trop. Parasitol. 2013 3 1 4 6 10.4103/2229‑5070.113884 23961435
    [Google Scholar]
  11. Kilkenny C. Browne W. Cuthill I.C. Emerson M. Altman D.G. Animal research: Reporting in vivo experiments: The ARRIVE guidelines. Br. J. Pharmacol. 2010 160 7 1577 1579 10.1111/j.1476‑5381.2010.00872.x 20649561
    [Google Scholar]
  12. Festing M.F.W. Altman D.G. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J. 2002 43 4 244 258 10.1093/ilar.43.4.244 12391400
    [Google Scholar]
  13. National Research Council (US) Committee Science, Medicine, and Animals. USA National Academies Press 2004 1 52
    [Google Scholar]
  14. Guidance for industry: Content and format of Investigational New Drug Applications (INDs) for phase 1 studies of drugs, including well-characterized, therapeutic, biotechnology-derived products. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm074980.pdf
  15. Anderson B.D. Conradi R.A. Predictive relationships in the water solubility of salts of a nonsteroidal anti-inflammatory drug. J. Pharm. Sci. 1985 74 8 815 820 10.1002/jps.2600740803 4032262
    [Google Scholar]
  16. US small business administration for the US environmental protection agency bridging the valley of death: Financing technology for a sustainable future. 1994 Available from: http://www.clu-in.org/download/supply/bridging.pdf
  17. Murphy LM Edwards PL Bridging the valley of death: Transitioning from public to private sector financing. 2003 Available from: http://www.cleanenergystates.org/CaseStudies/NREL Bridging_the_Valley_of_Death.pdf
  18. Wen H. Jung H. Li X. Drug delivery approaches in addressing clinical pharmacology-related issues: Opportunities and challenges. AAPS J. 2015 17 6 1327 1340 10.1208/s12248‑015‑9814‑9 26276218
    [Google Scholar]
  19. Gad S.C. Preclinical Development Handbook: ADME and Biopharmaceutical Properties. 1st ed Hoboken, NJ John Wiley and Sons, Inc. 2008
    [Google Scholar]
  20. Wu S. Hopkins W. Characterization of D-α tocopheryl PEG 1000 succinate for applications as an absorption enhancer in drug delivery systems. Pharm. Technol. 1999 23 52 68
    [Google Scholar]
  21. Rege B.D. Kao J.P.Y. Polli J.E. Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers. Eur. J. Pharm. Sci. 2002 16 4-5 237 246 10.1016/S0928‑0987(02)00055‑6 12208453
    [Google Scholar]
  22. Kuentz M. Nick S. Parrott N. Röthlisberger D. A strategy for preclinical formulation development using GastroPlus™ as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur. J. Pharm. Sci. 2006 27 1 91 99 10.1016/j.ejps.2005.08.011 16219449
    [Google Scholar]
  23. Wang J. Maitani Y. Takayama K. Antitumor effects and pharmacokinetics of aclacinomycin A carried by injectable emulsions composed of vitamin E, cholesterol, and PEG-lipid. J. Pharm. Sci. 2002 91 4 1128 1134 10.1002/jps.10104 11948551
    [Google Scholar]
  24. Itoh K. Matsui S. Tozuka Y. Oguchi T. Yamamoto K. Improvement of physicochemical properties of N-4472. Int. J. Pharm. 2002 246 1-2 75 83 10.1016/S0378‑5173(02)00346‑0 12270610
    [Google Scholar]
  25. Kan P. Chen Z.B. Lee C.J. Chu I.M. Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system. J. Control. Release 1999 58 3 271 278 10.1016/S0168‑3659(98)00164‑3 10099152
    [Google Scholar]
  26. Khoo S.M. Humberstone A.J. Porter C.J.H. Edwards G.A. Charman W.N. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int. J. Pharm. 1998 167 1-2 155 164 10.1016/S0378‑5173(98)00054‑4
    [Google Scholar]
  27. Khachane P. Date A.A. Nagarsenker M.S. Positively charged polymeric nanoparticles: Application in improving therapeutic efficacy of meloxicam after oral administration. Pharmazie 2011 66 5 334 338 21699066
    [Google Scholar]
  28. Lee M.J. Lee M.H. Shim C.K. Inverse targeting of drugs to reticuloendothelial system-rich organs by lipid microemulsion emulsified with poloxamer 338. Int. J. Pharm. 1995 113 2 175 187 10.1016/0378‑5173(94)00193‑9
    [Google Scholar]
  29. Kim S.J. Choi H.K. Lee Y.B. Pharmacokinetic and pharmacodynamic evaluation of cyclosporin A O/W-emulsion in rats. Int. J. Pharm. 2002 249 1-2 149 156 10.1016/S0378‑5173(02)00490‑8 12433443
    [Google Scholar]
  30. Li L. Nandi I. Kim K.H. Development of an ethyl laurate-based microemulsion for rapid-onset intranasal delivery of diazepam. Int. J. Pharm. 2002 237 1-2 77 85 10.1016/S0378‑5173(02)00029‑7 11955806
    [Google Scholar]
  31. Shah N.H. Carvajal M.T. Patel C.I. Infeld M.H. Malick A.W. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int. J. Pharm. 1994 106 1 15 23 10.1016/0378‑5173(94)90271‑2
    [Google Scholar]
  32. Rabinow B.E. Nanosuspensions in drug delivery. Nat. Rev. Drug Discov. 2004 3 9 785 796 10.1038/nrd1494 15340388
    [Google Scholar]
  33. Mutalik S. Naha A. Usha A.N. Ranjith A.K. Musmade P. Manoj K. Anju P. Prasanna S. Preparation, In vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac. Arch. Pharm. Res. 2007 30 2 222 234 10.1007/BF02977698 17366745
    [Google Scholar]
  34. Li P. Zhao L. Developing early formulations: Practice and perspective. Int. J. Pharm. 2007 341 1-2 1 19 10.1016/j.ijpharm.2007.05.049 17658228
    [Google Scholar]
  35. Law D. Schmitt E.A. Marsh K.C. Everitt E.A. Wang W. Fort J.J. Krill S.L. Qiu Y. Ritonavir-PEG 8000 amorphous solid dispersions: In vitro and in vivo evaluations. J. Pharm. Sci. 2004 93 3 563 570 10.1002/jps.10566 14762895
    [Google Scholar]
  36. Curry A. Brown R. The target product profile as a planning tool in drug discovery research. Pharmatech 2003 67 71
    [Google Scholar]
  37. Shah S.M. Jain A.S. Kaushik R. Nagarsenker M.S. Nerurkar M.J. Preclinical formulations: Insight, strategies, and practical considerations. AAPS PharmSciTech 2014 15 5 1307 1323 10.1208/s12249‑014‑0156‑1 24920522
    [Google Scholar]
  38. Dai W.G. Pollock-Dove C. Dong L.C. Li S. Advanced screening assays to rapidly identify solubility-enhancing formulations: High-throughput, miniaturization and automation. Adv. Drug Deliv. Rev. 2008 60 6 657 672 10.1016/j.addr.2007.10.017 18222563
    [Google Scholar]
  39. Date A.A. Desai N. Dixit R. Nagarsenker M. Self-nano emulsifying drug delivery systems: Formulation insights, applications and advances. Nanomedicine 2010 5 10 1595 1616 10.2217/nnm.10.126
    [Google Scholar]
  40. Kaushik R. Pisat N. Enose A. Nerurkar M.A. A 25 mg Approach for material characterization without automation. AAPS Annual Meeting and Exposition. National Biotechnology Conference Washington Convention Center, Seattle, 2009. p. M1206.
    [Google Scholar]
  41. The Biopharmaceutics Classification System (BCS) guidance. 2009 Available from: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm[updated 2009; cited].
  42. Alsenz J. Kansy M. High throughput solubility measurement in drug discovery and development. Adv. Drug Deliv. Rev. 2007 59 7 546 567 10.1016/j.addr.2007.05.007 17604872
    [Google Scholar]
  43. Saal C. Petereit A.C. Optimizing solubility: Kinetic versus thermodynamic solubility temptations and risks. Eur. J. Pharm. Sci. 2012 47 3 589 595 10.1016/j.ejps.2012.07.019 22885099
    [Google Scholar]
  44. Kulshreshtha A.K. Singh O.N. Wall G.M. Garad S. Wang J. Joshi Y. Preclinical development for suspensions. Pharmaceutical Suspensions New York Springer 2009 127 176 10.1007/978‑1‑4419‑1087‑5_5
    [Google Scholar]
  45. Guidance for industry, investigators, and reviewers; exploratory IND studies. 2006 Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078933.pdf[Accessed 31 Mar 2006].
  46. Niwa T. Hashimoto N. Novel technology to prepare oral formulations for preclinical safety studies. Int. J. Pharm. 2008 350 1-2 70 78 10.1016/j.ijpharm.2007.08.027 17942253
    [Google Scholar]
  47. Sherif I.B. Miriam K.F. Munir A.H. Salt selection for pharmaceutical compounds. Preformulation in solid dosage form development. 1st ed Adeyeye M.C. Brittain H.G. New York Informa Healthcare 2008 63 80
    [Google Scholar]
  48. Guerrieri P. Taylor L.S. Role of salt and excipient properties on disproportionation in the solid-state. Pharm. Res. 2009 26 8 2015 2026 10.1007/s11095‑009‑9918‑y 19507008
    [Google Scholar]
  49. Kesisoglou F. Panmai S. Wu Y. Nanosizing — Oral formulation development and biopharmaceutical evaluation. Adv. Drug Deliv. Rev. 2007 59 7 631 644 10.1016/j.addr.2007.05.003 17601629
    [Google Scholar]
  50. Bummer P. Interfacial phenomena. Remington: The Science and Practice of Pharmacy. Troy D. Baltimore Lippincott Williams and Wilkins 2006 280
    [Google Scholar]
  51. Grant R.L. Yao C. Gabaldon D. Acosta D. Evaluation of surfactant cytotoxicity potential by primary cultures of ocular tissues: I. Characterization of rabbit corneal epithelial cells and initial injury and delayed toxicity studies. Toxicology 1992 76 2 153 176 10.1016/0300‑483X(92)90162‑8 1281345
    [Google Scholar]
  52. Stella V.J. He Q. Cyclodextrins. Toxicol. Pathol. 2008 36 1 30 42 10.1177/0192623307310945 18337219
    [Google Scholar]
  53. Brewster M.E. Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 2007 59 7 645 666 10.1016/j.addr.2007.05.012 17601630
    [Google Scholar]
  54. Jain A.S. Date A.A. Pissurlenkar R.R.S. Coutinho E.C. Nagarsenker M.S. Sulfobutyl ether(7) β-cyclodextrin (SBE(7) β-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity. AAPS Pharm. Sci. Tech. 2011 12 4 1163 1175 10.1208/s12249‑011‑9685‑z 21918921
    [Google Scholar]
  55. Loftsson T. Duchêne D. Cyclodextrins and their pharmaceutical applications. Int. J. Pharm. 2007 329 1-2 1 11 10.1016/j.ijpharm.2006.10.044 17137734
    [Google Scholar]
  56. Nagarsenker M.S. Joshi M.S. Celecoxib-cyclodextrin systems: characterization and evaluation of in vitro and in vivo advantage. Drug Dev. Ind. Pharm. 2005 31 2 169 178 10.1081/DDC‑200047795 15773284
    [Google Scholar]
  57. Smith J.S. MacRae R.J. Snowden M.J. Effect of SBE7-β-cyclodextrin complexation on carbamazepine release from sustained release beads. Eur. J. Pharm. Biopharm. 2005 60 1 73 80 10.1016/j.ejpb.2004.12.001 15848059
    [Google Scholar]
  58. Crowley M.M. Fredersdorf A. Schroeder B. Kucera S. Prodduturi S. Repka M.A. McGinity J.W. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. Eur. J. Pharm. Sci. 2004 22 5 409 418 10.1016/j.ejps.2004.04.005 15265510
    [Google Scholar]
  59. Nagarsenker M.S. Meshram R.N. Ramprakash G. Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in anti-inflammatory activity and reduction in ulcerogenicity in rats. J. Pharm. Pharmacol. 2000 52 8 949 956 10.1211/0022357001774831 11007065
    [Google Scholar]
  60. Naima Z. Siro T. Juan-Manuel G.D. Chantal C. René C. Jerome D. Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures. Eur. J. Pharm. Sci. 2001 12 4 395 404 10.1016/S0928‑0987(00)00168‑8 11231106
    [Google Scholar]
  61. Sethia S. Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int. J. Pharm. 2004 272 1-2 1 10 10.1016/j.ijpharm.2003.11.025 15019063
    [Google Scholar]
  62. Williams M. Tian Y. Jones D.S. Andrews G.P. Hot-melt extrusion technology: optimizing drug delivery. Eur. Ind. Pharm. 2010 7 7 10
    [Google Scholar]
  63. Mensch J. Melis A. Mackie C. Verreck G. Brewster M.E. Augustijns P. Evaluation of various PAMPA models to identify the most discriminating method for the prediction of BBB permeability. Eur. J. Pharm. Biopharm. 2010 74 3 495 502 10.1016/j.ejpb.2010.01.003 20067834
    [Google Scholar]
  64. Boersen N. Lee T. Hui H-W. Faqi A.S. Chapter 4 - development of preclinical formulations for toxicology studies. A comprehensive guide to toxicology in preclinical drug development 1st Ed Faqi A.S. London Academic Press 2012 69 86
    [Google Scholar]
  65. Barrett E.R. Nanosuspensions for parenteral delivery. Nanoparticulate Drug Delivery Systems Boca Raton CRC Press 2007 33 50 10.1201/9781420008449.ch2
    [Google Scholar]
  66. Zerrouk N. Chemtob C. Arnaud P. Toscani S. Dugue J. In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions. Int. J. Pharm. 2001 225 1-2 49 62 10.1016/S0378‑5173(01)00741‑4 11489554
    [Google Scholar]
  67. Zhang X. Xia Q. Gu N. Preparation of All-Trans Retinoic Acid nanosuspensions using a modified precipitation method. Drug Dev. Ind. Pharm. 2006 32 7 857 863 10.1080/03639040500534184 16908423
    [Google Scholar]
  68. Keck C. Müller R. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur. J. Pharm. Biopharm. 2006 62 1 3 16 10.1016/j.ejpb.2005.05.009 16129588
    [Google Scholar]
  69. Müller R.H. Jacobs C. Kayser O. Nanosuspensions as particulate drug formulations in therapy. Adv. Drug Deliv. Rev. 2001 47 1 3 19 10.1016/S0169‑409X(00)00118‑6 11251242
    [Google Scholar]
  70. Tungaraza T.E. Talapan-Manikoth P. Jenkins R. Curse of the ghost pills: the role of oral controlled-release formulations in the passage of empty intact shells in faeces. Two case reports and a literature review relevant to psychiatry. Ther. Adv. Drug Saf. 2013 4 2 63 71 10.1177/2042098612474681 25083252
    [Google Scholar]
  71. Beaumont K. Webster R. Gardner I. Dack K. Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist. Curr. Drug Metab. 2003 4 6 461 485 10.2174/1389200033489253 14683475
    [Google Scholar]
  72. Dahan A. Zimmermann E.M. Ben-Shabat S. Modern prodrug design for targeted oral drug delivery. Molecules 2014 19 10 16489 16505 10.3390/molecules191016489
    [Google Scholar]
  73. Mahato R. Tai W. Cheng K. Prodrugs for improving tumor targetability and efficiency. Adv. Drug Deliv. Rev. 2011 63 8 659 670 10.1016/j.addr.2011.02.002 21333700
    [Google Scholar]
  74. Zawilska J.B. Wojcieszak J. Olejniczak A.B. Prodrugs: A challenge for the drug development. Pharmacol. Rep. 2013 65 1 1 14 10.1016/S1734‑1140(13)70959‑9 23563019
    [Google Scholar]
  75. Ulhane J.C. Dawson P.E. Peptide pharmaceuticals: modifications to the peptide backbone that enhance stability and targeting. Chim. Oggi. 2014 32 4 17 18
    [Google Scholar]
  76. Milla P. Dosio F. Cattel L. PEGylation of proteins and liposomes: a powerful and flexible strategy to improve the drug delivery. Curr. Drug Metab. 2012 13 1 105 119 10.2174/138920012798356934 21892917
    [Google Scholar]
  77. Pasut G. Morpurgo M. Veronese F.M. Basic strategies for PEGylation of peptide and protein drugs. Deliv. Prot. Pept. Drugs Cancer 2006 53 84 10.1142/9781860948039_0004
    [Google Scholar]
  78. Ishida T. Kiwada H. Anti-polyethyleneglycol antibody response to PEGylated substances. Biol. Pharm. Bull. 2013 36 6 889 891 10.1248/bpb.b13‑00107 23727911
    [Google Scholar]
  79. Schellekens H. Hennink W.E. Brinks V. The immunogenicity of polyethylene glycol: facts and fiction. Pharm. Res. 2013 30 7 1729 1734 10.1007/s11095‑013‑1067‑7 23673554
    [Google Scholar]
  80. Verhoef J.J.F. Carpenter J.F. Anchordoquy T.J. Schellekens H. Potential induction of anti-PEG antibodies and complement activation toward PEGylated therapeutics. Drug Discov. Today 2014 19 12 1945 1952 10.1016/j.drudis.2014.08.015 25205349
    [Google Scholar]
  81. Dawidczyk C.M. Kim C. Park J.H. Russell L.M. Lee K.H. Pomper M.G. Searson P.C. State-of-the-art in design rules for drug delivery platforms: Lessons learned from FDA-approved nanomedicines. J. Control. Release 2014 187 133 144 10.1016/j.jconrel.2014.05.036 24874289
    [Google Scholar]
  82. Dawidczyk C.M. Russell L.M. Searson P.C. Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments. Front Chem. 2014 2 69 10.3389/fchem.2014.00069 25202689
    [Google Scholar]
  83. Onoue S. Yamada S. Chan H-K. Nanodrugs: pharmacokinetics and safety. Int. J. Nanomed. 2014 9 1025 1037 10.2147/IJN.S38378
    [Google Scholar]
  84. Tiwari G. Tiwari R. Rai A. Cyclodextrins in delivery systems: Applications. J. Pharm. Bioallied Sci. 2010 2 2 72 79 10.4103/0975‑7406.67003 21814436
    [Google Scholar]
  85. Andersson S.B. Jonn S. Landh T. Nicotine compositions and methods of formulation thereof. Patent WO1999015171A1 1999
  86. Stefansson E. Loftsson T. Cyclodextrins in eye drop formulations. J. Incl. Phenom. Macrocycl. Chem. 2003 44 1–4 23 27
    [Google Scholar]
  87. Chan J.G.Y. Wong J. Zhou Q.T. Leung S.S.Y. Chan H.K. Advances in device and formulation technologies for pulmonary drug delivery. AAPS PharmSciTech 2014 15 4 882 897 10.1208/s12249‑014‑0114‑y 24728868
    [Google Scholar]
  88. Cheng Y.S. Mechanisms of pharmaceutical aerosol deposition in the respiratory tract. AAPS PharmSciTech 2014 15 3 630 640 10.1208/s12249‑014‑0092‑0 24563174
    [Google Scholar]
  89. Cordts E. Steckel H. Formulation considerations for dry powder inhalers. Ther. Deliv. 2014 5 6 675 689 10.4155/tde.14.35 25090281
    [Google Scholar]
  90. Cui Y Schmalfuß S. Zellnitz S. Towards the optimization and adaptation of dry powder inhalers. Int. J. Pharm. 2014 470 1-2 120 132 10.1016/j.ijpharm.2014.04.065
    [Google Scholar]
  91. Escárcega R.O. Baker N.C. Lipinski M.J. Magalhaes M.A. Minha S. Omar A.F. Torguson R. Waksman R. Current application and bioavailability of drug-eluting stents. Expert Opin. Drug Deliv. 2014 11 5 689 709 10.1517/17425247.2014.888054 24533457
    [Google Scholar]
  92. Wiebe J. Nef H.M. Hamm C.W. Current status of bioresorbable scaffolds in the treatment of coronary artery disease. J. Am. Coll. Cardiol. 2014 64 23 2541 2551 10.1016/j.jacc.2014.09.041 25500240
    [Google Scholar]
  93. Atkinson M.A. Eisenbarth G.S. Michels A.W. Type 1 diabetes. Lancet 2014 383 9911 69 82 10.1016/S0140‑6736(13)60591‑7 23890997
    [Google Scholar]
  94. Tauschmann M. Hovorka R. Insulin pump therapy in youth with type 1 diabetes: toward closed-loop systems. Expert Opin. Drug Deliv. 2014 11 6 943 955 10.1517/17425247.2014.910192 24749563
    [Google Scholar]
  95. Nagilla R. Nord M. Mcatee J.J. Jolivette L.J. Cassette dosing for pharmacokinetic screening in drug discovery: comparison of clearance, volume of distribution, half-life, mean residence time, and oral bioavailability obtained by cassette and discrete dosing in rats. J. Pharm. Sci. 2011 100 9 3862 3874 10.1002/jps.22525 21360708
    [Google Scholar]
  96. Chiou W.L. Barve A. Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharm. Res. 1998 15 11 1792 1795 10.1023/A:1011981317451 9834005
    [Google Scholar]
  97. Lui C.Y. Amidon G.L. Berardi R.R. Fleisher D. Youngberg C. Dressman J.B. Comparison of gastrointestinal pH in dogs and humans: implications on the use of the beagle dog as a model for oral absorption in humans. J. Pharm. Sci. 1986 75 3 271 274 10.1002/jps.2600750313 3701609
    [Google Scholar]
  98. Yamada I. Haga K. Measurement of gastric pH during digestion of a solid meal in dogs. Chem. Pharm. Bull. 1990 38 6 1755 1756 10.1248/cpb.38.1755 2208391
    [Google Scholar]
  99. Akimoto M. Nagahata N. Furuya A. Fukushima K. Higuchi S. Suwa T. Gastric pH profiles of beagle dogs and their use as an alternative to human testing. Eur. J. Pharm. Biopharm. 2000 49 2 99 102 10.1016/S0939‑6411(99)00070‑3 10704891
    [Google Scholar]
  100. Kesisoglou F. Mitra A. Crystalline nanosuspensions as potential toxicology and clinical oral formulations for BCS II/IV compounds. AAPS J. 2012 14 4 677 687 10.1208/s12248‑012‑9383‑0 22736294
    [Google Scholar]
  101. Higgins J. Cartwright M.E. Templeton A.C. Progressing preclinical drug candidates: strategies on preclinical safety studies and the quest for adequate exposure. Drug Discov. Today 2012 17 15-16 828 836 10.1016/j.drudis.2012.03.016 22546604
    [Google Scholar]
  102. Brewster M. Claire M. Noppe M. Lampo A. Loftsson T. The use of solubilizing excipients and approaches to generate toxicology vehicles for contemporary drug pipelines. Solvent systems and their selection in pharmaceutics and biopharmaceutics. Augustijns P. Brewster M. New York Springer 2007 221 256 10.1007/978‑0‑387‑69154‑1_8
    [Google Scholar]
  103. Sun Y.N. Lee H.J. Almon R.R. Jusko W.J. A pharmacokinetic/pharmacodynamic model for recombinant human growth hormone effects on induction of insulin-like growth factor I in monkeys. J. Pharmacol. Exp. Ther. 1999 289 3 1523 1532 10.1016/S0022‑3565(24)38301‑6 10336548
    [Google Scholar]
  104. Gabrielsson J. Green A.R. Van der Graaf P.H. Optimising in vivo pharmacology studies—Practical PKPD considerations. J. Pharmacol. Toxicol. Methods 2010 61 2 146 156 10.1016/j.vascn.2010.02.002 20153442
    [Google Scholar]
  105. Peterson J.K. Houghton P.J. Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development. Eur. J. Cancer 2004 40 6 837 844 10.1016/j.ejca.2004.01.003 15120039
    [Google Scholar]
  106. HoHoughton P.J. Houghton J.A Myers L. Cheshire P. Evaluation of N-(5-indanylsulfonyl)-N0-(4-chlorophenyl)-urea against xenografts of pediatric rhabdomyosarcoma. Cancer Chemother. Pharmacol. 1989 25 84 88 10.1007/BF00692344 2598403
    [Google Scholar]
  107. Houghton P.J. Cheshire P.J. Hallman J.C. Evaluation of a novel bis-naphthalimide anticancer agent DMP-840 against human xenograft derived from adult, juvenile, and pediatric cancers. Cancer Chemother. Pharmacol. 1994 36 45 52 10.1007/BF00685731 7720175
    [Google Scholar]
  108. Houghton P.J. Cheshire P.J. Hallman J.D. II Houghton J.A. Therapeutic efficacy of the cyclopropylpyrroloindole, carzelesin, against xenografts derived from adult and childhood solid tumors. Cancer Chemother. Pharmacol. 1995 36 1 45 52 10.1007/BF00685731 7720175
    [Google Scholar]
  109. Black P.L. Ussery M.A. Barney S. Wittrock R. DeMarsh P. Dreyer G.B. Petteway S.R. Jr DalMonte P. Baldoni J. Lambert D.M. Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in mice. Antiviral Res. 1996 29 2-3 175 186 10.1016/0166‑3542(95)00831‑4 8739597
    [Google Scholar]
  110. D’Souza R. Mutalik S. Venkatesh M. Vidyasagar S. Udupa N. Nasal insulin gel as an alternate to parenteral insulin: Formulation, preclinical, and clinical studies. AAPS PharmSciTech 2005 6 2 E184 E189 10.1208/pt060227 16353976
    [Google Scholar]
  111. Rathbone M.J. Purvesh R. Ghazail F.A. Ho P.C. In vivo techniques for studying the oral mucosal absorption characteristics of drugs in animals and humans. Oral mucosal drug delivery. Rathbone M.J. New York Marcel Dekker, Inc. 1996 121 156
    [Google Scholar]
  112. Dali M.M. Moench P.A. Mathias N.R. Stetsko P.I. Heran C.L. Smith R.L. A rabbit model for sublingual drug delivery: Comparison with human pharmacokinetic studies of propranolol, verapamil and captopril. J. Pharm. Sci. 2006 95 1 37 44 10.1002/jps.20312 16307454
    [Google Scholar]
  113. Kesavadev J. Das A.K. Unnikrishnan R. Joshi S.R. Ramachandran A. Shamsudeen J. Krishnan G. Jothydev S. Mohan V. Use of insulin pumps in India: suggested guidelines based on experience and cultural differences. Diabetes Technol. Ther. 2010 12 10 823 831 10.1089/dia.2010.0027 20807118
    [Google Scholar]
  114. Chopade P. Chopade N. Zhao Z. Mitragotri S. Liao R. Suja C.V. Alzheimer’s and Parkinson’s disease therapies in the clinic. Bioeng. Transl. Med. 2023 8 1 e10367 10.1002/btm2.10367 36684083
    [Google Scholar]
  115. Thomas R.H. Smith P.E.M. Epilepsy is different. J. R. Soc. Med. 2011 104 4 141 143 10.1258/jrsm.2011.100412 21502208
    [Google Scholar]
  116. Singh I. Thakur G. Singh A. Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin. Int. J. Pharm. Investig. 2016 6 1 23 31 10.4103/2230‑973X.176468 27014616
    [Google Scholar]
  117. Shivalingam M.R. Balasubramanian A. Ramalingam K. Formulation and evaluation of transdermal patches of pantoprazole sodium. Inter. J. App. Pharm. 2021 13 5 287 291 10.22159/ijap.2021v13i5.42175
    [Google Scholar]
  118. Crowe T.P. Hsu W.H. Evaluation of recent intranasal drug delivery systems to the central nervous system. Pharmaceutics 2022 14 3 629 10.3390/pharmaceutics14030629 35336004
    [Google Scholar]
  119. Stella B. Baratta F. Pepa D.C. Arpicco S. Gastaldi D. Dosio F. Cannabinoid formulations and delivery systems: Current and future options to treat pain. Drugs 2021 81 13 1513 1557 10.1007/s40265‑021‑01579‑x 34480749
    [Google Scholar]
  120. Laffleur F. Keckeis V. Advances in drug delivery systems: Work in progress still needed? Int. J. Pharm. 2020 590 119912 10.1016/j.ijpharm.2020.119912 32971178
    [Google Scholar]
  121. Diana J.N. Tao Y. Du Q. Wang M. Kumar C.U. Wu F. Jin T. PLGA microspheres of hGH of preserved native state prepared using a self-regulated process. Pharmaceutics 2020 12 7 683 10.3390/pharmaceutics12070683 32698347
    [Google Scholar]
  122. Lim H.S. Evolving role of modeling and simulation in drug development. Transl. Clin. Pharmacol. 2019 27 1 19 23 10.12793/tcp.2019.27.1.19 32055577
    [Google Scholar]
  123. Ding Y. Chu N. Wang R. Qin W. Shi Y. Qian Z. Liu B. He Q. Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects. Sci. Rep. 2024 14 1 7071 10.1038/s41598‑024‑57581‑2 38528026
    [Google Scholar]
  124. Jones L. Carol H. Evans K. Richmond J. Houghton P.J. Smith M.A. Lock R.B. A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Leukemia 2016 30 11 2133 2141 10.1038/leu.2016.192 27416986
    [Google Scholar]
  125. Graham C. Tucker C. Creech J. Favours E. Billups C.A. Liu T. Fouladi M. Freeman B.B. III Stewart C.F. Houghton P.J. Evaluation of the antitumor efficacy, pharmacokinetics, and pharmacodynamics of the histone deacetylase inhibitor depsipeptide in childhood cancer models in vivo. Clin. Cancer Res. 2006 12 1 223 234 10.1158/1078‑0432.CCR‑05‑1225 16397046
    [Google Scholar]
  126. Murphy B. Yin H. Maris J.M. Kolb E.A. Gorlick R. Reynolds C.P. Kang M.H. Keir S.T. Kurmasheva R.T. Dvorchik I. Wu J. Billups C.A. Boateng N. Smith M.A. Lock R.B. Houghton P.J. Evaluation of alternative in vivo drug screening methodology: a single mouse analysis. Cancer Res. 2016 76 19 5798 5809 10.1158/0008‑5472.CAN‑16‑0122 27496711
    [Google Scholar]
  127. Fehér A. Boross P. Sperka T. Miklóssy G. Kádas J. Bagossi P. Oroszlan S. Weber I.T. Tözsér J. Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease. J. Gen. Virol. 2006 87 5 1321 1330 10.1099/vir.0.81382‑0 16603535
    [Google Scholar]
  128. Blanc-Sylvestre N. Bouchard P. Chaussain C. Bardet C. Pre-clinical models in implant dentistry: past, present, future. Biomedicines 2021 9 11 1538 10.3390/biomedicines9111538 34829765
    [Google Scholar]
  129. Majid H. Bartel A. Burckhardt B.B. Predictivity of standardized and controlled permeation studies: Ex vivo – In vitro – In vivo correlation for sublingual absorption of propranolol. Eur. J. Pharm. Biopharm. 2021 169 12 19 10.1016/j.ejpb.2021.09.002 34508807
    [Google Scholar]
  130. Vick J.A. Kandil A. Herman E.H. Balazs T. Reversal of propranolol and verapamil toxicity by calcium. Vet. Hum. Toxicol. 1983 25 1 8 10 6829164
    [Google Scholar]
  131. Kreuter J. Ramge P. Petrov V. Hamm S. Gelperina S.E. Engelhardt B. Alyautdin R. Briesen V.H. Begley D.J. Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm. Res. 2003 20 3 409 416 10.1023/A:1022604120952 12669961
    [Google Scholar]
  132. Jensen S.A. Day E.S. Ko C.H. Hurley L.A. Luciano J.P. Kouri F.M. Merkel T.J. Luthi A.J. Patel P.C. Cutler J.I. Daniel W.L. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci. Transl. Med. 2020 5 209 209ra152 10.1126/scitranslmed.3006839
    [Google Scholar]
  133. Mathew A. Fukuda T. Nagaoka Y. Hasumura T. Morimoto H. Yoshida Y. Maekawa T. Venugopal K. Kumar D.S. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One 2012 7 3 e32616 10.1371/journal.pone.0032616 22403681
    [Google Scholar]
  134. Xin H. Jiang X. Gu J. Sha X. Chen L. Law K. Chen Y. Wang X. Jiang Y. Fang X. Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials 2011 32 18 4293 4305 10.1016/j.biomaterials.2011.02.044 21427009
    [Google Scholar]
  135. Liu H.L. Hua M.Y. Yang H.W. Huang C.Y. Chu P.C. Wu J.S. Tseng I.C. Wang J.J. Yen T.C. Chen P.Y. Wei K.C. Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain. Proc. Natl. Acad. Sci. USA 2010 107 34 15205 15210 10.1073/pnas.1003388107 20696897
    [Google Scholar]
  136. Hu K. Li J. Shen Y. Lu W. Gao X. Zhang Q. Jiang X. Lactoferrin-conjugated PEG–PLA nanoparticles with improved brain delivery: In vitro and in vivo evaluations. J. Control. Rel. 2009 134 1 55 61 10.1016/j.jconrel.2008.10.016 19038299
    [Google Scholar]
  137. Ruan S. Yuan M. Zhang L. Hu G. Chen J. Cun X. Zhang Q. Yang Y. He Q. Gao H. Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials 2015 37 425 435 10.1016/j.biomaterials.2014.10.007 25453970
    [Google Scholar]
  138. Oates J.T. Lopez D. Pharmacogenetics: an important part of drug development with a focus on its application. Int. J. Biomed. Investig. 2018 1 2 111 32467882
    [Google Scholar]
  139. Ezike T.C. Okpala U.S. Onoja U.L. Nwike C.P. Ezeako E.C. Okpara O.J. Okoroafor C.C. Eze S.C. Kalu O.L. Odoh E.C. Nwadike U.G. Ogbodo J.O. Umeh B.U. Ossai E.C. Nwanguma B.C. Advances in drug delivery systems, challenges and future directions. Heliyon 2023 9 6 e17488 10.1016/j.heliyon.2023.e17488 37416680
    [Google Scholar]
/content/journals/rrct/10.2174/0115748871340281250331180316
Loading
Transformative Paths: Preclinical Drug Formulation and Delivery Approaches in Development
Bentham Science Publishers ; https://doi.org/10.2174/0115748871340281250331180316
/content/journals/rrct/10.2174/0115748871340281250331180316
/content/journals/rrct/10.2174/0115748871340281250331180316
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Pre-clinical studies ; IND ; pre-formulation studies ; innovation ; regulatory approval ; formulation strategies

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test