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The expanding role of formulations to enable oral delivery of poorly water-soluble drugs

Nature Reviews Drug Discovery (2026)Cite this article

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Abstract

Contemporary small-molecule drug candidates increasingly have limited aqueous solubility, rendering oral delivery challenging. Amorphous solid dispersions (ASDs) and lipid-based formulations (LBFs) have evolved as leading formulation approaches to mitigate solubility and dissolution rate limitations. There is an increasing trend towards ASD formulations for drug candidates with high melting points and LBFs for extremely lipophilic molecules. Mechanistic assessment of LBF and ASD enhancement pathways reveals a surprising amount of commonality, notably that supersaturation generation and maintenance are likely key to obtaining optimized in vivo performance for both formulation types. An expanding formulation design space is blurring the distinction between these solubility enhancement technologies and further evolution in this direction is likely necessary to address the oral delivery of even more challenging molecules, such as proteolysis-targeting chimeras and macrocyclic peptides.

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Fig. 1: Composition of ASDs and LBFs, and key kinetic processes underpinning drug absorption from these formulations.
Fig. 2: Comparison of the use of LBFs and ASDs in approved products over time.
Fig. 3: Classification of supersaturation behaviour and drug concentrations in gastrointestinal tract fluids after dissolution/dispersion of ASDs and LBFs.

References

  1. Williams, H. D. et al. Strategies to address low drug solubility in discovery and development. Pharmacol. Rev. 65, 315–499 (2013).

    Article  PubMed  Google Scholar 

  2. Davis, M. E. & Brewster, M. E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug. Discov. 3, 1023–1035 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Porter, C. J., Trevaskis, N. L. & Charman, W. N. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat. Rev. Drug. Discov. 6, 231–248 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Gardner, C. R., Walsh, C. T. & Almarsson, Ö Drugs as materials: valuing physical form in drug discovery. Nat. Rev. Drug. Discov. 3, 926–934 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Datta, S. & Grant, D. J. W. Crystal structures of drugs: advances in determination, prediction and engineering. Nat. Rev. Drug. Discov. 3, 42–57 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Trevaskis, N. L., Kaminskas, L. M. & Porter, C. J. H. From sewer to saviour—targeting the lymphatic system to promote drug exposure and activity. Nat. Rev. Drug. Discov. 14, 781–803 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Feeney, O. M. et al. 50 years of oral lipid-based formulations: provenance, progress and future perspectives. Adv. Drug. Delivery Rev. 101, 167–194 (2016).

    Article  CAS  Google Scholar 

  8. Bergström, C. A., Charman, W. N. & Porter, C. J. Computational prediction of formulation strategies for beyond-rule-of-5 compounds. Adv. Drug. Delivery Rev. 101, 6–21 (2016).

    Article  Google Scholar 

  9. Wuelfing, W. P. et al. Dose number as a tool to guide lead optimization for orally bioavailable compounds in drug discovery. J. Medicinal Chem. 65, 1685–1694 (2022).

    Article  CAS  Google Scholar 

  10. Chen, X.-Q., Gudmundsson, O. S. & Hageman, M. J. Application of lipid-based formulations in drug discovery. J. Medicinal Chem. 55, 7945–7956 (2012).

    Article  CAS  Google Scholar 

  11. Hargrove, J. T., Maxson, W. S. & Wentz, A. C. Absorption of oral progesterone is influenced by vehicle and particle size. Am. J. Obstet. Gynecol. 161, 948–951 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Rácz, A. et al. The changing landscape of medicinal chemistry optimization. Nat. Rev. Drug Discov. 24, 870–887 (2025).

    Article  PubMed  Google Scholar 

  13. Klebe, G. Applying thermodynamic profiling in lead finding and optimization. Nat. Rev. Drug. Discov. 14, 95–110 (2015).

    Article  CAS  PubMed  Google Scholar 

  14. Keseru, G. M. & Makara, G. M. The influence of lead discovery strategies on the properties of drug candidates. Nat. Rev. Drug. Discov. 8, 203–212 (2009).

    Article  PubMed  Google Scholar 

  15. O’Brien Laramy, M. N., Luthra, S., Brown, M. F. & Bartlett, D. W. Delivering on the promise of protein degraders. Nat. Rev. Drug. Discov. 22, 410–427 (2023).

    Article  PubMed  Google Scholar 

  16. He, Y. F. et al. Radioactive ADME demonstrates ARV-110’s high druggability despite low oral bioavailability. J. Medicinal Chem. 67, 14277–14291 (2024).

    Article  CAS  Google Scholar 

  17. Poongavanam, V., Wieske, L. H. E., Peintner, S., Erdelyi, M. & Kihlberg, J. Molecular chameleons in drug discovery. Nat. Rev. Chem. 8, 45–60 (2024).

    Article  CAS  PubMed  Google Scholar 

  18. Valeur, E. et al. New modalities for challenging targets in drug discovery. Angew. Chem. Int. Ed. 56, 10294–10323 (2017).

    Article  CAS  Google Scholar 

  19. Blanco, M.-J., Gardinier, K. M. & Namchuk, M. N. Advancing new chemical modalities into clinical studies. ACS Medicinal Chem. Lett. 13, 1691–1698 (2022).

    Article  CAS  Google Scholar 

  20. Békés, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug. Discov. 21, 181–200 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Edmondson, S. D., Yang, B. & Fallan, C. Proteolysis targeting chimeras (PROTACs) in ‘beyond rule-of-five’ chemical space: recent progress and future challenges. Bioorg. Med. Chem. Lett. 29, 1555–1564 (2019).

    Article  CAS  PubMed  Google Scholar 

  22. Maple, H. J., Clayden, N., Baron, A., Stacey, C. & Felix, R. Developing degraders: principles and perspectives on design and chemical space. Medchemcomm 10, 1755–1764 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Vinogradov, A. A., Yin, Y. & Suga, H. Macrocyclic peptides as drug candidates: recent progress and remaining challenges. J. Am. Chem. Soc. 141, 4167–4181 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Räder, A. F. B. et al. Orally active peptides: is there a magic bullet? Angew. Chem. Int. Ed. 57, 14414–14438 (2018).

    Article  Google Scholar 

  25. Kawai, T. et al. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc. Natl Acad. Sci. USA 117, 29959–29967 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bar-Hai, A., Domb, A. J. & Hoffman, A. Strategies for enhancing the oral bioavailability of cannabinoids. Expert. Opin. Drug. Metab. Toxicol. 18, 313–322 (2022).

    Article  CAS  PubMed  Google Scholar 

  27. Pandi, P., Bulusu, R., Kommineni, N., Khan, W. & Singh, M. Amorphous solid dispersions: an update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int. J. Pharm. 586, 119560 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. He, Y. & Ho, C. Amorphous solid dispersions: utilization and challenges in drug discovery and development. J. Pharm. Sci. 104, 3237–3258 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Hiew, T. N., Zemlyanov, D. Y. & Taylor, L. S. Balancing solid-state stability and dissolution performance of lumefantrine amorphous solid dispersions: the role of polymer choice and drug–polymer interactions. Mol. Pharm. 19, 392–413 (2021).

    Article  PubMed  Google Scholar 

  30. Mosquera-Giraldo, L. I. et al. Crystallization inhibition properties of cellulose esters and ethers for a group of chemically diverse drugs: experimental and computational insight. Biomacromolecules 19, 4593–4606 (2018).

    Article  CAS  PubMed  Google Scholar 

  31. Moseson, D. E., Tran, T. B., Karunakaran, B., Ambardekar, R. & Hiew, T. N. Trends in amorphous solid dispersion drug products approved by the US Food and Drug Administration between 2012 and 2023. Int. J. Pharm. X 7, 100259 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Haser, A., DiNunzio, J. C., Martin, C., McGinity, J. W. & Zhang, F. in Formulating Poorly Water Soluble Drugs (eds Williams, R. O. III, Watts, A. B. & Miller, D. A.) 383–435 (Springer, 2016).

  33. Curatolo, W., Nightingale, J. & Herbig, S. Utility of hydroxypropylmethylcellulose acetate succinate (HPMCAS) for initiation and maintenance of drug supersaturation in the GI milieu. Pharm. Res. 26, 1419–1431 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Arca, H. C. et al. Pharmaceutical applications of cellulose ethers and cellulose ether esters. Biomacromolecules 19, 2351–2376 (2018).

    Article  CAS  PubMed  Google Scholar 

  35. McKelvey, C. A. & Kesisoglou, F. Enabling an HCV treatment revolution and the frontiers of solid solution formulation. J. Pharm. Sci. 108, 50–57 (2019).

    Article  CAS  PubMed  Google Scholar 

  36. Pouton, C. W. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the Lipid Formulation Classification System. Eur. J. Pharm. Sci. 29, 278–287 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Williams, H. D. et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new Lipid Formulation Performance Classification System. J. Pharm. Sci. 103, 2441–2455 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. Xi, H. et al. The effect of inorganic salt on disintegration of tablets with high loading of amorphous solid dispersion containing copovidone. Pharm. Res. 37, 1–13 (2020).

    Article  Google Scholar 

  39. Lenz, J., Finke, J. H., Bunjes, H., Kwade, A. & Juhnke, M. Tablet formulation development focusing on the functional behaviour of water uptake and swelling. Int. J. Pharm. X 3, 100103 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Indulkar, A. S., Lou, X., Zhang, G. G. Z. & Taylor, L. S. Insights into the dissolution mechanism of ritonavir–copovidone amorphous solid dispersions: importance of congruent release for enhanced performance. Mol. Pharm. 16, 1327–1339 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Taylor, L. S. & Zhang, G. G. Z. Physical chemistry of supersaturated solutions and implications for oral absorption. Adv. Drug. Delivery Rev. 101, 122–142 (2016).

    Article  CAS  Google Scholar 

  42. Wilson, V. et al. Relationship between amorphous solid dispersion in vivo absorption and in vitro dissolution: phase behavior during dissolution, speciation, and membrane mass transport. J. Control. Release 292, 172–182 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Friesen, D. T. et al. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol. Pharm. 5, 1003–1019 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. Ilevbare, G. A. & Taylor, L. S. Liquid–liquid phase separation in highly supersaturated aqueous solutions of poorly water-soluble drugs: implications for solubility enhancing formulations. Cryst. Growth Des. 13, 1497–1509 (2013).

    Article  CAS  Google Scholar 

  45. Paus, R., Ji, Y., Vahle, L. & Sadowski, G. Predicting the solubility advantage of amorphous pharmaceuticals: a novel thermodynamic approach. Mol. Pharm. 12, 2823–2833 (2015).

    Article  CAS  PubMed  Google Scholar 

  46. Narula, A., Sabra, R. & Li, N. Mechanisms and extent of enhanced passive permeation by colloidal drug particles. Mol. Pharm. 19, 3085–3099 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ueda, K., Takemoto, S., Higashi, K. & Moribe, K. Impact of colloidal drug-rich droplet size and amorphous solubility on drug membrane permeability: a comprehensive analysis. J. Pharm. Sci. 114, 136–144 (2025).

    Article  CAS  PubMed  Google Scholar 

  48. Yoshikawa, E., Ueda, K., Hakata, R., Higashi, K. & Moribe, K. Quantitative investigation of intestinal drug absorption enhancement by drug-rich nanodroplets generated via liquid–liquid phase separation. Mol. Pharm. 21, 1745–1755 (2024).

    Article  CAS  PubMed  Google Scholar 

  49. Stewart, A. M. & Grass, M. E. Practical approach to modeling the impact of amorphous drug nanoparticles on the oral absorption of poorly soluble drugs. Mol. Pharm. 17, 180–189 (2019).

    Article  PubMed  Google Scholar 

  50. Suys, E. J., Brundel, D. H., Chalmers, D. K., Pouton, C. W. & Porter, C. J. Interaction with biliary and pancreatic fluids drives supersaturation and drug absorption from lipid-based formulations of low (saquinavir) and high (fenofibrate) permeability poorly soluble drugs. J. Control. Release 331, 45–61 (2021).

    Article  CAS  PubMed  Google Scholar 

  51. Anby, M. U. et al. Lipid digestion as a trigger for supersaturation: evaluation of the impact of supersaturation stabilization on the in vitro and in vivo performance of self-emulsifying drug delivery systems. Mol. Pharm. 9, 2063–2079 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. Yeap, Y. Y. et al. Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation. Mol. Pharm. 10, 1874–1889 (2013).

    Article  CAS  PubMed  Google Scholar 

  53. Yeap, Y. Y., Trevaskis, N. L. & Porter, C. J. Lipid absorption triggers drug supersaturation at the intestinal unstirred water layer and promotes drug absorption from mixed micelles. Pharm. Res. 30, 3045–3058 (2013).

    Article  CAS  PubMed  Google Scholar 

  54. Edera, R., Ueda, K., Tomita, S., Higashi, K. & Moribe, K. Impact of microemulsion oil components on liquid–liquid phase separation of a supersaturated drug revealed by cryo-TEM and 1H NMR analysis. Mol. Pharm. 22, 1539–1554 (2025).

    Article  CAS  PubMed  Google Scholar 

  55. Gao, P. & Morozowich, W. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert. Opin. Drug Delivery 3, 97–110 (2006).

    Article  CAS  Google Scholar 

  56. Gao, P. et al. Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability. J. Pharm. Sci. 92, 2386–2398 (2003).

    Article  CAS  PubMed  Google Scholar 

  57. Van Eerdenbrugh, B., Raina, S., Hsieh, Y.-L., Augustijns, P. & Taylor, L. Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments. Pharm. Res. 31, 969–982 (2014).

    Article  PubMed  Google Scholar 

  58. Crum, M. F., Trevaskis, N. L., Pouton, C. W. & Porter, C. J. Transient supersaturation supports drug absorption from lipid-based formulations for short periods of time, but ongoing solubilization is required for longer absorption periods. Mol. Pharm. 14, 394–405 (2017).

    Article  CAS  PubMed  Google Scholar 

  59. Taylor, L. S. et al. Changes in drug crystallinity in a commercial tacrolimus amorphous formulation result in variable pharmacokinetics. J. Pharm. Sci. 114, 313–322 (2025).

    Article  CAS  PubMed  Google Scholar 

  60. Mateo, J. et al. An adaptive study to determine the optimal dose of the tablet formulation of the PARP inhibitor olaparib. Target. Oncol. 11, 401–415 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Lorenz, D. A. et al. Formulations of enzalutamide. US Patent 20170027910 (2017).

  62. Potharaju, S. et al. Improving solubility and oral bioavailability of a novel antimalarial prodrug: comparing spray-dried dispersions with self-emulsifying drug delivery systems. Pharm. Dev. Technol. 25, 625–639 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Khoo, S.-M., Porter, C. J. & Charman, W. N. The formulation of halofantrine as either non-solubilising PEG 6000 or solubilising lipid based solid dispersions: physical stability and absolute bioavailability assessment. Int. J. Pharm. 205, 65–78 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Zhang, Z., Lu, Y., Qi, J. & Wu, W. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharm. Sin. B 11, 2449–2468 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Reddiar, S. B. et al. Intestinal lymphatic biology, drug delivery, and therapeutics: current status and future directions. Pharmacol. Rev. 76, 1326–1398 (2024).

    Article  CAS  PubMed  Google Scholar 

  66. Baluk, P. et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J. Exp. Med. 204, 2349–2362 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Caliph, S. M., Charman, W. N. & Porter, C. J. Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. J. Pharm. Sci. 89, 1073–1084 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Charman, W. & Stella, V. Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules. Int. J. Pharm. 34, 175–178 (1986).

    Article  CAS  Google Scholar 

  69. Porter, C. J. & Charman, W. N. Uptake of drugs into the intestinal lymphatics after oral administration. Adv. Drug Delivery Rev. 25, 71–89 (1997).

    Article  CAS  Google Scholar 

  70. Zgair, A. et al. Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Sci. Rep. 7, 14542 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Hu, L. et al. Glyceride-mimetic prodrugs incorporating self-immolative spacers promote lymphatic transport, avoid first-pass metabolism, and enhance oral bioavailability. Angew. Chem. Int. Ed. 55, 13700–13705 (2016).

    Article  CAS  Google Scholar 

  72. Cao, E. et al. Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity. Nat. Metab. 3, 1175–1188 (2021).

    Article  CAS  PubMed  Google Scholar 

  73. Nora, G.-I. et al. Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug. J. Control. Release 349, 206–212 (2022).

    Article  CAS  PubMed  Google Scholar 

  74. Bannow, J., Yorulmaz, Y., Löbmann, K., Müllertz, A. & Rades, T. Improving the drug load and in vitro performance of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) using polymeric precipitation inhibitors. Int. J. Pharm. 575, 118960 (2020).

    Article  CAS  PubMed  Google Scholar 

  75. Holm, R., Kuentz, M., Ilie-Spiridon, A.-R. & Griffin, B. T. Lipid based formulations as supersaturating oral delivery systems: from current to future industrial applications. Eur. J. Pharm. Sci. 189, 106556 (2023).

    Article  CAS  PubMed  Google Scholar 

  76. Chemburkar, S. R. et al. Dealing with the impact of ritonavir polymorphs on the late stages of bulk drug process development. Org. Process. Res. Dev. 4, 413–417 (2000).

    Article  CAS  Google Scholar 

  77. Williams, H. D. et al. Unlocking the full potential of lipid-based formulations using lipophilic salt/ionic liquid forms. Adv. Drug Delivery Rev. 142, 75–90 (2019).

    Article  CAS  Google Scholar 

  78. Koehl, N. J. et al. Lipophilic salts and lipid-based formulations for bridging the food effect gap of venetoclax. J. Pharm. Sci. 111, 164–174 (2022).

    Article  CAS  PubMed  Google Scholar 

  79. Sahbaz, Y. et al. Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. Mol. Pharm. 12, 1980–1991 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Klein, C. E. et al. The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J. Acquir. Immune Defic. Syndr. 44, 401–410 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Schittny, A., Philipp-Bauer, S., Detampel, P., Huwyler, J. & Puchkov, M. Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions. J. Control. Release 320, 214–225 (2020).

    Article  CAS  PubMed  Google Scholar 

  82. Gao, P. et al. Characterization and optimization of AMG 517 supersaturatable self-emulsifying drug delivery system (S-SEDDS) for improved oral absorption. J. Pharm. Sci. 98, 516–528 (2009).

    Article  CAS  PubMed  Google Scholar 

  83. Dobry, D. E. et al. A model-based methodology for spray-drying process development. J. Pharm. Innov. 4, 133–142 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Dohrn, S. et al. Predicting process design spaces for spray drying amorphous solid dispersions. Int. J. Pharm. X 3, 100072 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Wolbert, F., Luebbert, C. & Sadowski, G. The shelf life of ASDs: 2. Predicting the shelf life at storage conditions. Int. J. Pharm. X 6, 100207 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Hu, H., Koranne, S., Bower, C. M., Skomski, D. & Lamm, M. S. High-speed imaging-based particle attribute analysis of spray-dried amorphous solid dispersions using a convolution neural network. Mol. Pharm. 22, 488–497 (2024).

    Article  PubMed  Google Scholar 

  87. Schmitt, J. M., Baumann, J. M. & Morgen, M. M. Predicting spray dried dispersion particle size via machine learning regression methods. Pharm. Res. 39, 3223–3239 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Gollob, J., Davis, J., McDonald, A. & Rong, H. Irak4 degraders and uses thereof. US Patent 12171768 (2022).

  89. Ackerman, L. et al. IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat. Med. 29, 3127–3136 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Savla, R., Browne, J., Plassat, V., Wasan, K. M. & Wasan, E. K. Review and analysis of FDA approved drugs using lipid-based formulations. Drug. Dev. Ind. Pharm. 43, 1743–1758 (2017).

    Article  CAS  PubMed  Google Scholar 

  91. O’Shea, J. P., Holm, R., O’Driscoll, C. M. & Griffin, B. T. Food for thought: formulating away the food effect—a PEARRL review. J. Pharm. Pharmacol. 71, 510–535 (2019).

    Article  PubMed  Google Scholar 

  92. Larfors, G. et al. Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug–drug interactions. Eur. J. Haematol. 111, 644–654 (2023).

    Article  CAS  PubMed  Google Scholar 

  93. Chen, S., Lotz, R. R. H., Schlesinger, E. B., Smithey, D. T. & Wald, R. J. Solid dispersion of a HER2 inhibitor. AU Patent 2023410266 (2024).

  94. Badawy, S. I. F. et al. Dosage forms for TYK2 inhibitors. CA Patent 3151137 (2021).

  95. Fry, D. S. et al. Solid dispersions of a erb2 (her2) inhibitor. US Patent 20140296267 (2014).

  96. Lange, J. J. et al. Comparative analysis of chemical descriptors by machine learning reveals atomistic insights into solute–lipid interactions. Mol. Pharm. 21, 3343–3355 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bannigan, P., Hickman, R. J., Aspuru-Guzik, A. & Allen, C. The dawn of a new pharmaceutical epoch: can AI and robotics reshape drug formulation? Adv. Healthc. Mater. 13, 2401312 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Karkare, R. Solid dosage forms and dosing regimens comprising (2R,3S,4S,5R)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide. CA Patent 3222197 (2022).

  99. Salama, P., Mamluk, R., Marom, K., Weinstein, I. & Tzabari, M. Pharmaceutical composition comprising octreotide oral suspension for improved delivery and therapeutic uses thereof. CA Patent 2963659 (2020).

  100. Heade, J., Maher, S., Bleiel, S. B. & Brayden, D. J. Labrasol® and salts of medium-chain fatty acids can be combined in low concentrations to increase the permeability of a macromolecule marker across isolated rat intestinal mucosae. J. Pharm. Sci. 107, 1648–1655 (2018).

    Article  CAS  PubMed  Google Scholar 

  101. McCartney, F., Caisse, P., Dumont, C. & Brayden, D. J. Capryol® 90 is an efficacious intestinal absorption enhancer for insulin in vivo when combined other excipients. Int. J. Pharm. 686, 126315 (2025).

    Article  CAS  PubMed  Google Scholar 

  102. McCartney, F. et al. Labrasol® is an efficacious intestinal permeation enhancer across rat intestine: ex vivo and in vivo rat studies. J. Control. Release 310, 115–126 (2019).

    Article  CAS  PubMed  Google Scholar 

  103. Noh, G. et al. Recent progress in hydrophobic ion-pairing and lipid-based drug delivery systems for enhanced oral delivery of biopharmaceuticals. J. Pharm. Investig. 52, 75–93 (2022).

    Article  CAS  Google Scholar 

  104. Wibel, R. et al. Oral delivery of calcitonin-ion pairs: in vivo proof of concept for a highly lipophilic counterion. Int. J. Pharm. 631, 122476 (2023).

    Article  CAS  PubMed  Google Scholar 

  105. Li, P. et al. Lipophilic salts and lipid-based formulations: enhancing the oral delivery of octreotide. Pharm. Res. 38, 1125–1137 (2021).

    Article  CAS  PubMed  Google Scholar 

  106. Postina, A., To, D., Zöller, K. & Bernkop-Schnürch, A. Oral peptide drug delivery: design of SEDDS providing a protective effect against intestinal membrane-bound enzymes. Drug Deliv. Transl. Res. https://doi.org/10.1007/s13346-025-01852-6 (2025).

  107. Menzel, C. et al. In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide. J. Control. Release 277, 165–172 (2018).

    Article  CAS  PubMed  Google Scholar 

  108. Venkatasubramanian, R. et al. Design, evaluation, and in vitro–in vivo correlation of self-nanoemulsifying drug delivery systems to improve the oral absorption of exenatide. J. Control. Release 379, 440–451 (2025).

    Article  CAS  PubMed  Google Scholar 

  109. Indulkar, A. S., Hanouch, L., Gignac, N., Borchardt, T. & Marsh, K. Investigating the effect of permeation enhancers on oral absorption of a BCS IV compound, ombitasvir, utilizing animal models. J. Pharm. Sci. 114, 103851 (2025).

    Article  CAS  PubMed  Google Scholar 

  110. Goole, J. et al. The effects of excipients on transporter mediated absorption. Int. J. Pharm. 393, 17–31 (2010).

    Article  CAS  PubMed  Google Scholar 

  111. Gurjar, R. et al. Inhibitory effects of commonly used excipients on P-glycoprotein in vitro. Mol. Pharm. 15, 4835–4842 (2018).

    Article  CAS  PubMed  Google Scholar 

  112. Gaikwad, V. L., Sen, S. G. & Dhake, P. R. Interactions between multifunctional pharmaceutical excipients and efflux pump for optimal drug transport and bioavailability: an overview. J. Drug. Delivery Sci. Technol. 94, 105475 (2024).

    Article  CAS  Google Scholar 

  113. Leeson, P. D. Molecular inflation, attrition and the rule of five. Adv. Drug. Delivery Rev. 101, 22–33 (2016).

    Article  CAS  Google Scholar 

  114. Burns, L. J. Glp1 pharmaceutical compositions. AU Patent 2023269995 (2023).

  115. Aburub, A., Allgeier, M. C., Hanson, J. M. & Huang, S. Pharmaceutical tablet composition containing glucagon-like peptide-1 for treating type 2 diabetes mellitus. AU Patent 2023269191 (2023).

  116. Niessen, J. et al. A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats. Eur. J. Pharm. Biopharm. 211, 114719 (2025).

    Article  CAS  PubMed  Google Scholar 

  117. Haskell, R. J. III & Reo, J. P. Solid oral dosage forms of estrogen receptor degraders. CA Patent 3295229 (2024).

  118. Dong, H. et al. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same. AU Patent 2021273458 (2021).

  119. Saraswat, A. et al. Oral lipid nanocomplex of BRD4 PROteolysis TArgeting Chimera and vemurafenib for drug-resistant malignant melanoma. Biomed. Pharmacother. 168, 115754 (2023).

    Article  CAS  PubMed  Google Scholar 

  120. Ueda, K., Moseson, D. E. & Taylor, L. S. Amorphous solubility advantage: theoretical considerations, experimental methods, and contemporary relevance. J. Pharm. Sci. 114, 18–39 (2025).

    Article  CAS  PubMed  Google Scholar 

  121. Elkhabaz, A., Moseson, D. E., Brouwers, J., Augustijns, P. & Taylor, L. S. Interplay of supersaturation and solubilization: lack of correlation between concentration-based supersaturation measurements and membrane transport rates in simulated and aspirated human fluids. Mol. Pharm. 16, 5042–5053 (2019).

    Article  CAS  PubMed  Google Scholar 

  122. Kraml, M., Dubuc, J., Beall, D. & L’Heureux, N. Gastrointestinal absorption of griseofulvin: I. Effect of particle size, addition of surfactants, and corn oil on the level of griseofulvin in the serum of rats. Can. J. Biochem. Physiol. 40, 1449–1451 (1962).

    Article  CAS  Google Scholar 

  123. Bates, T. R., Gibaldi, M. & Kanig, J. L. Solubilizing properties of bile salt solutions II. Effect of inorganic electrolyte, lipids, and a mixed bile salt system on solubilization of glutethimide, griseofulvin, and hexestrol. J. Pharm. Sci. 55, 901–906 (1966).

    Article  CAS  PubMed  Google Scholar 

  124. Bates, T. R. & Sequeira, J. A. Bioavailability of micronized griseofulvin from corn oil-in-water emulsion, aqueous suspension, and commercial tablet dosage forms in humans. J. Pharm. Sci. 64, 793–797 (1975).

    Article  CAS  PubMed  Google Scholar 

  125. Svenson, S., Delorenzo, W., Engelberg, R., Spooner, M. & Randall, L. Absorption and chemotherapeutic activity of acetyl sulfisoxazole suspended in an oil in water emulsion. Antibiotic Med. Clin. Ther. 2, 148–152 (1956).

    CAS  Google Scholar 

  126. Daeschner, C. W., Bell, W. R., Stivrins, P. C., Yow, E. M. & Townsend, E. Oral sulfonamides in lipid emulsion: a comparative study of free sulfonamide levels in blood following oral administration of sulfonamides in aqueous suspension and in lipid emulsions to infants and children. AMA J. Dis. Child. 93, 370–374 (1957).

    Article  CAS  PubMed  Google Scholar 

  127. Kovarik, J. M., Mueller, E. A., Kutz, K., Van Bree, J. B. & Tetzloff, W. Reduced inter-and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation. J. Pharm. Sci. 83, 444–446 (1994).

    Article  CAS  PubMed  Google Scholar 

  128. Tay, E. et al. Ionic liquid forms of the antimalarial lumefantrine in combination with LFCS type IIIB lipid-based formulations preferentially increase lipid solubility, in vitro solubilization behavior and in vivo exposure. Pharmaceutics 12, 17 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Dahan, A. & Hoffman, A. The effect of different lipid based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. Eur. J. Pharm. Biopharm. 67, 96–105 (2007).

    Article  CAS  PubMed  Google Scholar 

  130. Taheri, A. et al. Enhancing the pharmacokinetics of abiraterone acetate through lipid-based formulations: addressing solubility and food effect challenges. Drug Deliv. Transl. Res. 15, 3770–3782 (2024).

    Article  PubMed  Google Scholar 

  131. Chavan, R. B., Modi, S. R. & Bansal, A. K. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. Int. J. Pharm. 495, 374–384 (2015).

    Article  CAS  PubMed  Google Scholar 

  132. Tanaka, Y., Doi, H., Katano, T. & Kasaoka, S. The impact of quantity of lipid based formulations with different compositions on the oral absorption of ritonavir: a trade-off between apparent solubility and permeability. Eur. J. Pharm. Sci. 168, 106079 (2022).

    Article  CAS  PubMed  Google Scholar 

  133. McEvoy, C. L. et al. In vitro–in vivo evaluation of lipid based formulations of the CETP inhibitors CP-529,414 (torcetrapib) and CP-532,623. Eur. J. Pharm. Biopharm. 88, 973–985 (2014).

    Article  CAS  PubMed  Google Scholar 

  134. Sek, L., Boyd, B. J., Charman, W. N. & Porter, C. J. Examination of the impact of a range of pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone. J. Pharm. Pharmacol. 58, 809–820 (2006).

    Article  CAS  PubMed  Google Scholar 

  135. Perlman, M. et al. Development of a self-emulsifying formulation that reduces the food effect for torcetrapib. Int. J. Pharm. 351, 15–22 (2008).

    Article  CAS  PubMed  Google Scholar 

  136. Li, H. et al. Dissolution evaluation in vitro and bioavailability in vivo of self-microemulsifying drug delivery systems for pH-sensitive drug loratadine. J. Microencapsul. 32, 175–180 (2015).

    Article  PubMed  Google Scholar 

  137. Nielsen, F. S., Petersen, K. B. & Müllertz, A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur. J. Pharm. Biopharm. 69, 553–562 (2008).

    Article  CAS  PubMed  Google Scholar 

  138. Lee, S.-M., Lee, J.-G., Yun, T.-H., Cho, J.-H. & Kim, K.-S. Enhanced stability and improved oral absorption of enzalutamide with self-nanoemulsifying drug delivery system. Int. J. Mol. Sci. 25, 1197 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Kotta, S. et al. Efavirenz nanoemulsion: formulation optimization by Box–Behnken design, in vivo pharmacokinetic evaluation and stability assessment. Int. J. Pharmacol. 18, 732–745 (2022).

    Article  CAS  Google Scholar 

  140. Charman, W. N., Rogge, M. C., Boddy, A. W., Barr, W. H. & Berger, B. M. Absorption of danazol after administration to different sites of the gastrointestinal tract and the relationship to single-and double-peak phenomena in the plasma profiles. J. Clin. Pharmacol. 33, 1207–1213 (1993).

    Article  CAS  PubMed  Google Scholar 

  141. Porter, C. J., Kaukonen, A. M., Boyd, B. J., Edwards, G. A. & Charman, W. N. Susceptibility to lipase-mediated digestion reduces the oral bioavailability of danazol after administration as a medium-chain lipid-based microemulsion formulation. Pharm. Res. 21, 1405–1412 (2004).

    Article  CAS  PubMed  Google Scholar 

  142. Larsen, A., Holm, R., Pedersen, M. L. & Müllertz, A. Lipid-based formulations for danazol containing a digestible surfactant, Labrafil M2125CS: in vivo bioavailability and dynamic in vitro lipolysis. Pharm. Res. 25, 2769–2777 (2008).

    Article  CAS  PubMed  Google Scholar 

  143. Chesney, E. et al. Novel lipid formulation increases absorption of oral cannabidiol (CBD). Pharmaceutics 16, 1537 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Izgelov, D. et al. Pharmacokinetic investigation of synthetic cannabidiol oral formulations in healthy volunteers. Eur. J. Pharm. Biopharm. 154, 108–115 (2020).

    Article  CAS  PubMed  Google Scholar 

  145. Lemberger, L. et al. Pharmacokinetics, metabolism and drug-abuse potential of nabilone. Cancer Treat. Rev. 9, 17–23 (1982).

    Article  PubMed  Google Scholar 

  146. Newman, A., Knipp, G. & Zografi, G. Assessing the performance of amorphous solid dispersions. J. Pharm. Sci. 101, 1355–1377 (2012).

    Article  CAS  PubMed  Google Scholar 

  147. Kwong, A. D., Kauffman, R. S., Hurter, P. & Mueller, P. Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. Nat. Biotech. 29, 993–1003 (2011).

    Article  CAS  Google Scholar 

  148. Bollag, G. et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596–599 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Kaufman, M. D., Bone, S., Bloom, C. & Jordan, F. Amorphous kinase inhibitor formulations and methods of use thereof. US Patent 20210196692 (2021).

  150. Hurter, P. Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide. AU Patent 2006332726 (2008).

  151. Gu, C.-H. Pharmaceutical compositions and use of (S)-N-((S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide. CA Patent 2942072 (2015).

  152. Brandhuber, B. J. et al. Spray-dried dispersions and formulations of (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoro propan-2-yl)-1H-pyrazole-4-carboxamide. AU Patent 2019314302 (2020).

  153. Yamashita, K. et al. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int. J. Pharm. 267, 79–91 (2003).

    Article  CAS  PubMed  Google Scholar 

  154. Dumas, J., Ehrlich, P. & Zuleger, S. Pharmaceutical compositions for the treatment of hyperproliferative disorders. US Patent 20060058358 (2006).

  155. Bechtold, M. K. et al. Pharmaceutical formulation 514. CA Patent 2737400 (2010).

  156. Mogalian, E., Oliyai, R., Stefanidis, D. & Zia, V. Solid dispersion formulation of an antiviral compound. US Patent 20140212487 (2014).

  157. Lowinger, M. et al. Composition of a non-nucleoside reverse transcriptase inhibitor. CA Patent 2929499 (2015).

  158. Harmon, P. A. & Variankaval, N. Solid dosage formulations of orexin receptor antagonist suvorexant. CA Patent 2795550 (2013).

  159. Choudhari, A., Thallur Gopi, A. K., Pattanayek, S., Shah, P. & Joshi, M. Eltrombopag choline dosage forms. US Patent 20220079883 (2022).

  160. Fang, L. Y., Harris, D. & Wan, J. Oral pharmaceutical compositions in a molecular solid dispersion. CA Patent 2720851 (2009).

  161. Wertz, C. F. & Chen, T. Pharmaceutical compositions and crushable tablets including amorphous solid dispersions of dasatinib and uses. US Patent 20230041852 (2023).

  162. Shah, N. et al. Improved human bioavailability of vemurafenib, a practically insoluble drug, using an amorphous polymer-stabilized solid dispersion prepared by a solvent-controlled coprecipitation process. J. Pharm. Sci. 102, 967–981 (2013).

    Article  CAS  PubMed  Google Scholar 

  163. Jain, J. P., Leong, F. J., Winnips, C. & Wolf, M.-C. Therapeutic regimen for malaria using an imidazolepiperazine optionally in combination with another antimalarial drug. US Patent 20180303837 (2018).

  164. Almeida e Sousa, L., Reutzel-Edens, S. M., Stephenson, G. A. & Taylor, L. S. Assessment of the amorphous “solubility” of a group of diverse drugs using new experimental and theoretical approaches. Mol. Pharm. 12, 484–495 (2014).

    Article  PubMed  Google Scholar 

  165. Crowley, K. J. & Zografi, G. Water vapor absorption into amorphous hydrophobic drug/poly(vinylpyrrolidone) dispersions. J. Pharm. Sci. 91, 2150–2165 (2002).

    Article  CAS  PubMed  Google Scholar 

  166. Bhujbal, S. V. et al. Pharmaceutical amorphous solid dispersion: a review of manufacturing strategies. Acta Pharm. Sin. B 11, 2505–2536 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Newman, A. & Zografi, G. Considerations in the development of physically stable high drug load API–polymer amorphous solid dispersions in the glassy state. J. Pharm. Sci. 112, 8–18 (2023).

    Article  CAS  PubMed  Google Scholar 

  168. Miller, D. A. & Keen, J. M. in Amorphous Solid Dispersions: Theory and Practice (eds Shah, N. et al.) 567–577 (Springer, 2014).

  169. Strotman, N. A. & Schenck, L. Coprecipitated amorphous dispersions as drug substance: opportunities and challenges. Org. Process. Res. Dev. 26, 10–13 (2021).

    Article  Google Scholar 

  170. Mudie, D. M. et al. Novel high-drug-loaded amorphous dispersion tablets of posaconazole; in vivo and in vitro assessment. Mol. Pharmaceutics 17, 4463–4472 (2020).

    Article  CAS  Google Scholar 

  171. Mudie, D. M. et al. A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets. Int. J. Pharm. X 2, 100042 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Vehring, R. Pharmaceutical particle engineering via spray drying. Pharm. Res. 25, 999–1022 (2008).

    Article  CAS  PubMed  Google Scholar 

  173. Paudel, A., Worku, Z. A., Meeus, J., Guns, S. & Van den Mooter, G. Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int. J. Pharm. 453, 253–284 (2013).

    Article  CAS  PubMed  Google Scholar 

  174. Ekdahl, A., Mudie, D., Malewski, D., Amidon, G. & Goodwin, A. Effect of spray-dried particle morphology on mechanical and flow properties of felodipine in PVP VA amorphous solid dispersions. J. Pharm. Sci. 108, 3657–3666 (2019).

    Article  CAS  PubMed  Google Scholar 

  175. Kossor, C., Bhat, R. & Davé, R. N. Assessing processability of milled HME extrudates: consolidating the effect of extrusion temperature, drug loading, and particle size via non-dimensional cohesion. Int. J. Pharm. 666, 124833 (2024).

    Article  CAS  PubMed  Google Scholar 

  176. Nakmode, D. et al. Fundamental aspects of lipid-based excipients in lipid-based product development. Pharmaceutics 14, 831 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Williams, H. D. et al. Lipid-based formulations and drug supersaturation: harnessing the unique benefits of the lipid digestion/absorption pathway. Pharm. Res. 30, 2976–2992 (2013).

    Article  CAS  PubMed  Google Scholar 

  178. Kuentz, M. Drug supersaturation during formulation digestion, including real-time analytical approaches. Adv. Drug Delivery Rev. 142, 50–61 (2019).

    Article  CAS  Google Scholar 

  179. Williams, H. D. et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. Pharm. Res. 30, 3059–3076 (2013).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

C.J.H.P. acknowledges funding from National Health and Medical Research Council Investigator Grant APP1177084 and Australian Research Council Linkage Grant LP220200944.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan

    Keisuke Ueda

  2. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia

    Christopher J. H. Porter

  3. Department of Pharmaceutical Sciences, OnKure Therapeutics, Boulder, CO, USA

    Aaron Goodwin

  4. Industrial and Molecular Pharmaceutics, Purdue University, West Lafayette, IN, USA

    Lynne S. Taylor

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  1. Keisuke Ueda
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  2. Christopher J. H. Porter
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  4. Lynne S. Taylor
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K.U. and C.J.H.P. were involved in conceptualization, writing the original draft, review and editing of the article, and literature analysis. A.G. was involved in conceptualization, writing the original draft, and review and editing of the article. L.S.T. was involved in conceptualization, writing the original draft, review and editing of the article, and literature analysis and editing.

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Correspondence to Lynne S. Taylor.

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Competing interests

C.J.H.P. is an inventor on intellectual property (IP) related to a triglyceride-mimetic prodrug technology that is briefly described in this Perspective and was licensed from Monash University to Seaport Therapeutics. L.S.T. has served as a consultant or paid speaker, may own shares or has received recent research funding from the following companies whose products are mentioned in this submission: Pfizer, Eli Lilly, AstraZeneca, Bristol Myers Squibb, Johnson and Johnson, AbbVie and Merck. The remaining authors declare no competing interests.

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Ueda, K., Porter, C.J.H., Goodwin, A. et al. The expanding role of formulations to enable oral delivery of poorly water-soluble drugs. Nat Rev Drug Discov (2026). https://doi.org/10.1038/s41573-026-01407-5

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