Skip to content
2000
image of Aprepitant: Review on Solubility Enhancement

Abstract

Introduction

Substance P and its neurokinin (NK-1) receptors are upregulated in different pathophysiological conditions. Overexpression of the NK-1 receptor in cancer conditions has provided a promising pathway for cancer treatment. Clinically, Aprepitant (APT) is used as the only NK-1 antagonist in chemotherapy-induced nausea and vomiting (CINV). Currently, investigations into using APT as a synergistic combination with radiation or standard chemotherapeutic drugs are underway. However, APT is categorised as a BCS Class IV drug, and therefore, solubility is one of the challenges when it must be delivered parenterally. The present review aims to understand the solubility enhancement techniques for better bioavailability.

Methods

Research and review articles were sought to understand the chemistry and solubility enhancement techniques reported for APT. Search engines such as Science Direct, PubMed, Bentham, and Google Scholar were used with the keywords “Aprepitant, solubility, NK1 receptor, parenteral dosage form.”

Results

The review comprehensively discusses the methods to improve the solubility of APT using innovative technologies, including nanotechnology.

Discussion

The review highlights the challenges associated with the use of APT in treating chemotherapy-induced nausea and vomiting (CINV), as well as its potential as a promising anticancer agent. While various solubility enhancement techniques can be employed for the oral administration of APT, the appropriate use of excipients and stability are essential for its safe clinical use in parenteral dosage forms.

Conclusion

The available solubility enhancement techniques discussed come with benefits and limitations. Fosaprepitant, a prodrug, is preferably used as an IV dosage form. Similarly, modification to a prodrug and solubility-enhancing excipients for nanoformulation can help make APT a promising therapy.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/raddf/10.2174/0126673878374342250708153111
2025-07-21
2025-09-05

  • From This Site

    /content/journals/raddf/10.2174/0126673878374342250708153111
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Robinson P. Coveñas R. Muñoz M. Combination therapy of chemotherapy or radiotherapy and the neurokinin-1 receptor antagonist aprepitant: A new antitumor strategy? Curr. Med. Chem. 2023 30 16 1798 1812 10.2174/0929867329666220811152602 35959620
    [Google Scholar]
  2. Kastin A.J. Handbook of Biologically Active Peptides. 2nd ed Academic Press Amsterdam, The Netherlands 2013
    [Google Scholar]
  3. Muñoz M. Coveñas R. Involvement of substance P and the NK-1 receptor in cancer progression. Peptides 2013 48 1 9 10.1016/j.peptides.2013.07.024 23933301
    [Google Scholar]
  4. Coveñas R. Muñoz M. Involvement of the substance P/Neurokinin-1 receptor system in cancer. Cancers 2022 14 14 3539 10.3390/cancers14143539 35884599
    [Google Scholar]
  5. Garcia-Recio S. Gascón P. Biological and pharmacological aspects of the NK1-receptor. BioMed Res. Int. 2015 2015 1 14 10.1155/2015/495704 26421291
    [Google Scholar]
  6. Muñoz M. Coveñas R. Neurokinin-1 receptor antagonists as anticancer drugs. Lett. Drug Des. Discov. 2019 16 10 1110 1129 10.2174/1570180816666190221091955
    [Google Scholar]
  7. Navari R.M. Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--Two new agents. J. Support. Oncol. 2003 1 2 89 103 15352652
    [Google Scholar]
  8. Coveñas R Rodríguez FD Muñoz M The Neurokinin-1 receptor: A promising antitumor target. Receptors 2022 1 1 72 79 10.3390/receptors1010005
    [Google Scholar]
  9. Muñoz M. Rosso M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest. New Drugs 2010 28 2 187 193 10.1007/s10637‑009‑9218‑8 19148578
    [Google Scholar]
  10. Kitchens C.A. McDonald P.R. Pollack I.F. Wipf P. Lazo J.S. Synergy between microtubule destabilizing agents and neurokinin 1 receptor antagonists identified by an siRNA synthetic lethal screen. FASEB J. 2009 23 S1 756 13 10.1096/fasebj.23.1_supplement.756.13
    [Google Scholar]
  11. Rodríguez F.D. Coveñas R. Antitumor strategies targeting peptidergic systems. Encyclopedia 2024 4 1 478 487 10.3390/encyclopedia4010031
    [Google Scholar]
  12. Muñoz M Coveñas R Safety of neurokinin-1 receptor antagonists. Expert Opin. Drug Saf. 2013 12 5 673 685 10.1517/14740338.2013.804059
    [Google Scholar]
  13. Hale J.J. Mills S.G. MacCoss M. Finke P.E. Cascieri M.A. Sadowski S. Ber E. Chicchi G.G. Kurtz M. Metzger J. Eiermann G. Tsou N.N. Tattersall F.D. Rupniak N.M.J. Williams A.R. Rycroft W. Hargreaves R. MacIntyre D.E. Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist. J. Med. Chem. 1998 41 23 4607 4614 10.1021/jm980299k 9804700
    [Google Scholar]
  14. Navari R.M. Reinhardt R.R. Gralla R.J. Kris M.G. Hesketh P.J. Khojasteh A. Kindler H. Grote T.H. Pendergrass K. Grunberg S.M. Carides A.D. Gertz B.J. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. N. Engl. J. Med. 1999 340 3 190 195 10.1056/NEJM199901213400304 9917226
    [Google Scholar]
  15. Gralla R.J. Osoba D. Kris M.G. Kirkbride P. Hesketh P.J. Chinnery L.W. Clark-Snow R. Gill D.P. Groshen S. Grunberg S. Koeller J.M. Morrow G.R. Perez E.A. Silber J.H. Pfister D.G. Recommendations for the use of antiemetics: Evidence-based, clinical practice guidelines. J. Clin. Oncol. 1999 17 9 2971 2994 10.1200/JCO.1999.17.9.2971 10561376
    [Google Scholar]
  16. Grunberg S.M. Hansen M. Deuson R. Incidence and impact of nausea/vomiting with modern antiemetics: Perception vs. reality. Cancer 2004 100 2261 2268 10.1002/cncr.20230 15139073
    [Google Scholar]
  17. Muñoz M. Coveñas R. The neurokinin-1 receptor antagonist aprepitant: An intelligent bullet against cancer? Cancers 2020 12 9 2682 10.3390/cancers12092682 32962202
    [Google Scholar]
  18. Cheng L. Wong H. Food effects on oral drug absorption: Application of physiologically-based pharmacokinetic modeling as a predictive tool. Pharmaceutics 2020 12 7 672 10.3390/pharmaceutics12070672 32708881
    [Google Scholar]
  19. Shono Y. Jantratid E. Kesisoglou F. Reppas C. Dressman J.B. Forecasting in vivo oral absorption and food effect of micronized and nanosized aprepitant formulations in humans. Eur. J. Pharm. Biopharm. 2010 76 1 95 104 10.1016/j.ejpb.2010.05.009 20576487
    [Google Scholar]
  20. Wu Y. Loper A. Landis E. Hettrick L. Novak L. Lynn K. Chen C. Thompson K. Higgins R. Batra U. Shelukar S. Kwei G. Storey D. The role of biopharmaceutics in the development of a clinical nanoparticle formulation of MK-0869: A Beagle dog model predicts improved bioavailability and diminished food effect on absorption in human. Int. J. Pharm. 2004 285 1-2 135 146 10.1016/j.ijpharm.2004.08.001 15488686
    [Google Scholar]
  21. USP Monographs, Aprepitant. USP-NF. Rockville, MD United States Pharmacopeia 2023 10.31003/USPNF_M753_03_01
    [Google Scholar]
  22. Boyd B.J. Bergström C.A.S. Vinarov Z. Kuentz M. Brouwers J. Augustijns P. Brandl M. Bernkop-Schnürch A. Shrestha N. Préat V. Müllertz A. Bauer-Brandl A. Jannin V. Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems. Eur. J. Pharm. Sci. 2019 137 104967 10.1016/j.ejps.2019.104967 31252052
    [Google Scholar]
  23. Ren L. Zhou Y. Wei P. Li M. Chen G. Preparation and pharmacokinetic study of aprepitant-sulfobutyl ether-β-cyclodextrin complex. AAPS PharmSciTech 2014 15 1 121 130 10.1208/s12249‑013‑0044‑0 24166668
    [Google Scholar]
  24. Ridhurkar D.N. Ansari K.A. Kumar D. Kaul N.S. Krishnamurthy T. Dhawan S. Pillai R. Inclusion complex of aprepitant with cyclodextrin: Evaluation of physico-chemical and pharmacokinetic properties. Drug Dev. Ind. Pharm. 2013 39 11 1783 1792 10.3109/03639045.2012.737331 23240730
    [Google Scholar]
  25. Cole E.T. Cadé D. Benameur H. Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration. Adv. Drug Deliv. Rev. 2008 60 6 747 756 10.1016/j.addr.2007.09.009 18096270
    [Google Scholar]
  26. Sigfridsson K. Ahlqvist M. Lindsjö M. Paulsson S. Salt formation improved the properties of a candidate drug during early formulation development. Eur. J. Pharm. Sci. 2018 120 162 171 10.1016/j.ejps.2018.04.048 29730322
    [Google Scholar]
  27. Yeo S. An J. Park C. Kim D. Lee J. Design and characterization of phosphatidylcholine-based solid dispersions of aprepitant for enhanced solubility and dissolution. Pharmaceutics 2020 12 5 407 10.3390/pharmaceutics12050407 32365589
    [Google Scholar]
  28. Roos C. Dahlgren D. Sjögren E. Sjöblom M. Hedeland M. Lennernäs H. Jejunal absorption of aprepitant from nanosuspensions: Role of particle size, prandial state and mucus layer. Eur. J. Pharm. Biopharm. 2018 132 132 222 230 10.1016/j.ejpb.2018.09.022 30266667
    [Google Scholar]
  29. Humberstone A.J. Charman W.N. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv. Drug Deliv. Rev. 1997 25 1 103 128 10.1016/S0169‑409X(96)00494‑2
    [Google Scholar]
  30. Nayak A.K. Panigrahi P.P. Solubility enhancement of etoricoxib by solvency approach. ISRN Physical Chemistry 2012 2012 1 5 10.5402/2012/820653
    [Google Scholar]
  31. Sui J. Luo Y. Zhai J. Fan F. Zhang L. Lu J. Zhu X. Solubility measurement, model evaluation and molecular simulations of aprepitant (form I) in eight pure solvents. J. Mol. Liq. 2020 304 112723 10.1016/j.molliq.2020.112723
    [Google Scholar]
  32. Sodeifian G. Sajadian S.A. Ardestani N.S. Determination of solubility of Aprepitant (an antiemetic drug for chemotherapy) in supercritical carbon dioxide: Empirical and thermodynamic models. J. Supercrit. Fluids 2017 128 102 111 10.1016/j.supflu.2017.05.019
    [Google Scholar]
  33. Madsen C.M. Feng K.I. Leithead A. Canfield N. Jørgensen S.A. Müllertz A. Rades T. Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. Eur. J. Pharm. Sci. 2018 111 311 319 10.1016/j.ejps.2017.10.003 28986196
    [Google Scholar]
  34. Angi R. Solymosi T. Ötvös Z. Ordasi B. Glavinas H. Filipcsei G. Heltovics G. Darvas F. Novel continuous flow technology for the development of a nanostructured Aprepitant formulation with improved pharmacokinetic properties. Eur. J. Pharm. Biopharm. 2014 86 3 361 368 10.1016/j.ejpb.2013.10.004 24161498
    [Google Scholar]
  35. Khadra I. Zhou Z. Dunn C. Wilson C.G. Halbert G. Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs. Eur. J. Pharm. Sci. 2015 67 65 75 10.1016/j.ejps.2014.10.019 25444845
    [Google Scholar]
  36. Benet L.Z. Broccatelli F. Oprea T.I. BDDCS applied to over 900 drugs. AAPS J. 2011 13 4 519 547 10.1208/s12248‑011‑9290‑9 21818695
    [Google Scholar]
  37. Serajuddin A.T.M. Salt formation to improve drug solubility. Adv. Drug Deliv. Rev. 2007 59 7 603 616 10.1016/j.addr.2007.05.010 17619064
    [Google Scholar]
  38. Rautio J. Meanwell N.A. Di L. Hageman M.J. The expanding role of prodrugs in contemporary drug design and development. Nat. Rev. Drug Discov. 2018 17 8 559 587 10.1038/nrd.2018.46 29700501
    [Google Scholar]
  39. Yadav GV Singh SR Nanosuspension: A promising drug delivery system. Pharmacophore 2012 3 5-2012 217 243
    [Google Scholar]
  40. Wu K Kwon SH Zhou X Fuller C Wang X Vadgama J Wu Y Overcoming challenges in small-molecule drug bioavailability: A review of key factors and approaches. Int J Mol Sci 2024 25 23 13121 10.3390/ijms252313121 39684832
    [Google Scholar]
  41. Wissing S.A. Kayser O. Müller R.H. Solid lipid nanoparticles for parenteral drug delivery. Adv. Drug Deliv. Rev. 2004 56 9 1257 1272 10.1016/j.addr.2003.12.002 15109768
    [Google Scholar]
  42. Ferreira L. Campos J. Veiga F. Cardoso C. Paiva-Santos A.C. Cyclodextrin-based delivery systems in parenteral formulations: A critical update review. Eur. J. Pharm. Biopharm. 2022 178 35 52 10.1016/j.ejpb.2022.07.007 35868490
    [Google Scholar]
  43. Kalepu S Nekkanti V Insoluble drug delivery strategies: Review of recent advances and business prospects. Acta. Pharm. Sin. B. 2015 5 5 442 453 10.1016/j.apsb.2015.07.003
    [Google Scholar]
  44. Shegokar R. Müller R.H. Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives. Int. J. Pharm. 2010 399 1-2 129 139 10.1016/j.ijpharm.2010.07.044 20674732
    [Google Scholar]
  45. 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]
  46. Salazar J. Müller R.H. Möschwitzer J.P. Combinative particle size reduction technologies for the production of drug nanocrystals. J. Pharm. 2014 2014 1 1 14 10.1155/2014/265754 26556191
    [Google Scholar]
  47. Thorat Y.S. Gonjari I.D. Hosmani A.H. Solubility enhancement techniques: A review on conventional and novel approaches. Int. J. Pharm. Sci. Res. 2011 2 10 2501 10.13040/IJPSR.0975‑8232.2(10).2501‑13
    [Google Scholar]
  48. Vemula V.R. Lagishetty V. Lingala S. Solubility enhancement techniques. Int. J. Pharm. Sci. Res. 2010 1 41 51
    [Google Scholar]
  49. Goel S. Sachdeva M. Agarwal V. Nanosuspension technology: Recent patents on drug delivery and their characterizations. Recent Pat. Drug Deliv. Formul. 2019 13 2 91 104 10.2174/1872211313666190614151615 31203813
    [Google Scholar]
  50. Agrawal Y.K. Patel V.R. Nanosuspension: An approach to enhance solubility of drugs. J. Adv. Pharm. Technol. Res. 2011 2 2 81 87 10.4103/2231‑4040.82950 22171298
    [Google Scholar]
  51. Liu J. Li S. Ao W. Li Y. Xiao Y. Bai M. Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability. Biochem. Biophys. Res. Commun. 2022 631 72 77 10.1016/j.bbrc.2022.09.031 36179498
    [Google Scholar]
  52. Toziopoulou F. Malamatari M. Nikolakakis I. Kachrimanis K. Production of aprepitant nanocrystals by wet media milling and subsequent solidification. Int. J. Pharm. 2017 533 2 324 334 10.1016/j.ijpharm.2017.02.065 28257885
    [Google Scholar]
  53. Attari Z. Kalvakuntla S. Reddy M.S. Deshpande M. Rao C.M. Koteshwara K.B. Formulation and characterisation of nanosuspensions of BCS class II and IV drugs by combinative method. J. Exp. Nanosci. 2016 11 4 276 288 10.1080/17458080.2015.1055841
    [Google Scholar]
  54. Roos C. Dahlgren D. Berg S. Westergren J. Abrahamsson B. Tannergren C. Sjögren E. Lennernäs H. In vivo mechanisms of intestinal drug absorption from aprepitant nanoformulations. Mol. Pharm. 2017 14 12 4233 4242 10.1021/acs.molpharmaceut.7b00294 28737398
    [Google Scholar]
  55. Kalvakuntla S. Deshpande M. Attari Z. Kunnatur B K. Preparation and characterization of nanosuspension of aprepitant by H96 process. Adv. Pharm. Bull. 2016 6 1 83 90 10.15171/apb.2016.013 27123422
    [Google Scholar]
  56. Kazi M. Al-Swairi M. Ahmad A. Raish M. Alanazi F.K. Badran M.M. Khan A.A. Alanazi A.M. Hussain M.D. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitro and in vivo assessment. Front. Pharmacol. 2019 10 459 10.3389/fphar.2019.00459 31118895
    [Google Scholar]
  57. Date A.A. Desai N. Dixit R. Nagarsenker M. Self-nanoemulsifying drug delivery systems: Formulation insights, applications and advances. Nanomedicine 2010 5 10 1595 1616 10.2217/nnm.10.126 21143036
    [Google Scholar]
  58. Rehman F.U. Shah K.U. Shah S.U. Khan I.U. Khan G.M. Khan A. From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS). Expert Opin. Drug Deliv. 2017 14 11 1325 1340 10.1080/17425247.2016.1218462 27485144
    [Google Scholar]
  59. Nazlı H. Mesut B. Akbal-Dağıstan Ö. Özsoy Y. A novel semi-solid self-emulsifying formulation of aprepitant for oral delivery: An in vitro evaluation. Pharmaceutics 2023 15 5 1509 10.3390/pharmaceutics15051509 37242751
    [Google Scholar]
  60. Nazlı H. Mesut B. Özsoy Y. In vitro evaluation of a solid supersaturated self-nanoemulsifying drug delivery system (Super-SNEDDS) of aprepitant for enhanced solubility. Pharmaceuticals 2021 14 11 1089 10.3390/ph14111089 34832871
    [Google Scholar]
  61. Alskär L.C. Porter C.J.H. Bergström C.A.S. Tools for early prediction of drug loading in lipid-based formulations. Mol. Pharm. 2016 13 1 251 261 10.1021/acs.molpharmaceut.5b00704 26568134
    [Google Scholar]
  62. Pandey V. Haider T. Agrawal P. Soni S. Soni V. Advances in natural polymeric nanoparticles for the drug delivery. In: Advances in Drug Delivery Methods United Kingdom IntechOpen 2022 10.5772/intechopen.107513
    [Google Scholar]
  63. Krishnamoorthy K. Mahalingam M. Selection of a suitable method for the preparation of polymeric nanoparticles: Multi-criteria decision making approach. Adv. Pharm. Bull. 2015 5 1 57 67 10.5681/apb.2015.008 25789220
    [Google Scholar]
  64. Sodeifian G. Sajadian S.A. Daneshyan S. Preparation of Aprepitant nanoparticles (efficient drug for coping with the effects of cancer treatment) by rapid expansion of supercritical solution with solid cosolvent (RESS-SC). J. Supercrit. Fluids 2018 140 72 84 10.1016/j.supflu.2018.06.009
    [Google Scholar]
  65. Li Y. Mou Y. Zhu Y. Liu J. Liu J. Zhao H. Equilibrium solubility determination and thermodynamic aspects of aprepitant (form I) in four binary aqueous mixtures of methanol, ethanol, acetone and 1,4-dioxane. J. Chem. Thermodyn. 2020 149 106170 10.1016/j.jct.2020.106170
    [Google Scholar]
  66. Suhail N. Alzahrani A.K. Basha W.J. Kizilbash N. Zaidi A. Ambreen J. Khachfe H.M. Microemulsions: Unique properties, pharmacological applications, and targeted drug delivery. Front. Nanotechnol. 2021 3 754889 10.3389/fnano.2021.754889
    [Google Scholar]
  67. Callender S.P. Mathews J.A. Kobernyk K. Wettig S.D. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery. Int. J. Pharm. 2017 526 1-2 425 442 10.1016/j.ijpharm.2017.05.005 28495500
    [Google Scholar]
  68. Ghai D. Sinha V.R. Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β1-adrenoreceptor blocker Talinolol. Nanomedicine 2012 8 5 618 626 10.1016/j.nano.2011.08.015 21924224
    [Google Scholar]
  69. Singh K. Tiwary A.K. Rana V. Spray dried chitosan–EDTA superior microparticles as solid substrate for the oral delivery of amphotericin B. Int. J. Biol. Macromol. 2013 58 310 319 10.1016/j.ijbiomac.2013.04.053 23624284
    [Google Scholar]
  70. Bandyopadhyay S. Katare O.P. 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 10.1016/j.colsurfb.2012.05.019 22766282
    [Google Scholar]
  71. Kamboj S. Sharma R. Singh K. Rana V. Aprepitant loaded solid preconcentrated microemulsion for enhanced bioavailability: A comparison with micronized Aprepitant. Eur. J. Pharm. Sci. 2015 78 90 102 10.1016/j.ejps.2015.07.008 26165621
    [Google Scholar]
  72. Pathak A Singh D Bedi N. Aprepitant loaded self-microemulsion preconcentrates for enhanced solubility and bioavailability: A design. Curr. Nanomed. 2018 8 2 156 173 10.2174/2468187308666180426120823
    [Google Scholar]
  73. Kamboj S. Rana V. Formulation optimization of aprepitant microemulsion-loaded silicated corn fiber gum particles for enhanced bioavailability. Drug Dev. Ind. Pharm. 2016 42 8 1267 1282 10.3109/03639045.2015.1122611 26592754
    [Google Scholar]
  74. Liu J. Zou M. Piao H. Liu Y. Tang B. Gao Y. Ma N. Cheng G. Characterization and pharmacokinetic study of aprepitant solid dispersions with soluplus®. Molecules 2015 20 6 11345 11356 10.3390/molecules200611345 26102068
    [Google Scholar]
  75. Sathigari S.K. Radhakrishnan V.K. Davis V.A. Parsons D.L. Babu R.J. Amorphous-state characterization of efavirenz--polymer hot-melt extrusion systems for dissolution enhancement. J. Pharm. Sci. 2012 101 9 3456 3464 10.1002/jps.23125 22437488
    [Google Scholar]
  76. Shah S. Maddineni S. Lu J. Repka M.A. Melt extrusion with poorly soluble drugs. Int. J. Pharm. 2013 453 1 233 252 10.1016/j.ijpharm.2012.11.001 23178213
    [Google Scholar]
  77. Kalivoda A. Fischbach M. Kleinebudde P. Application of mixtures of polymeric carriers for dissolution enhancement of fenofibrate using hot-melt extrusion. Int. J. Pharm. 2012 429 1-2 58 68 10.1016/j.ijpharm.2012.03.009 22440149
    [Google Scholar]
  78. Penumetcha S.S. Gutta L.N. Dhanala H. Yamili S. Challa S. Rudraraju S. Rudraraju S. Rudraraju V. Hot melt extruded Aprepitant–Soluplus solid dispersion: Preformulation considerations, stability and in vitro study. Drug Dev. Ind. Pharm. 2016 42 10 1609 1620 10.3109/03639045.2016.1160105 26925514
    [Google Scholar]
  79. Loftsson T. Cyclodextrins in parenteral formulations. J. Pharm. Sci. 2021 110 2 654 664 10.1016/j.xphs.2020.10.026 33069709
    [Google Scholar]
  80. Pardeshi C.V. Kothawade R.V. Markad A.R. Pardeshi S.R. Kulkarni A.D. Chaudhari P.J. Longhi M.R. Dhas N. Naik J.B. Surana S.J. García M.C. Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications. Carbohydr. Polym. 2023 301 Pt B 120347 10.1016/j.carbpol.2022.120347 36446486
    [Google Scholar]
  81. Erdoğar N. Akkın S. Nielsen T.T. Özçelebi E. Erdoğdu B. Nemutlu E. İskit A.B. Bilensoy E. Development of oral aprepitant-loaded chitosan–polyethylene glycol-coated cyclodextrin nanocapsules: Formulation, characterization, and pharmacokinetic evaluation. J. Pharm. Investig. 2021 51 3 297 310 10.1007/s40005‑020‑00511‑x
    [Google Scholar]
  82. Palmelund H. Eriksen J.B. Bauer-Brandl A. Rantanen J. Löbmann K. Enabling formulations of aprepitant: in vitro and in vivo comparison of nanocrystalline, amorphous and deep eutectic solvent based formulations. Int. J. Pharm. X 2021 3 100083 10.1016/j.ijpx.2021.100083 34151250
    [Google Scholar]
  83. Li Y. Yin H. Wu C. He J. Wang C. Ren B. Wang H. Geng D. Zhang Y. Zhao L. Preparation and in vivo evaluation of an intravenous emulsion loaded with an aprepitant-phospholipid complex. Drug Deliv. 2023 30 1 2183834 10.1080/10717544.2023.2183834 36843571
    [Google Scholar]
  84. Li Y Wu J Lu Q Liu X Wen J Qi X Liu J Lian B Zhang B Sun H Tian G. GA GA&HA-modified liposomes for co-delivery of aprepitant and curcumin to inhibit drug-resistance and metastasis of hepatocellular carcinoma. Inter. J. Nanomed. 2022 2559 2575 10.2147/IJN.S381649
    [Google Scholar]
  85. Vijetha J. Balamurugan K. Formulation and evaluation of lipid nanoparticulate drug delivery system of aprepitant for the treatment of CINV. J. Pharm. Negat. Results 2022 13 10
    [Google Scholar]
  86. Lale A.S. Sirvi A. Debaje S. Patil S. Sangamwar A.T. Supersaturable diacyl phospholipid dispersion for improving oral bioavailability of brick dust molecule: A case study of Aprepitant. Eur. J. Pharm. Biopharm. 2024 197 114241 10.1016/j.ejpb.2024.114241 38432600
    [Google Scholar]
  87. Liu J. Li Y. Ao W. Xiao Y. Bai M. Li S. Preparation and characterization of aprepitant solid dispersion with HPMCAS-LF. ACS Omega 2022 7 44 39907 39912 10.1021/acsomega.2c04021 36385804
    [Google Scholar]
  88. Punčochová K. Ewing A.V. Gajdošová M. Pekárek T. Beránek J. Kazarian S.G. Štěpánek F. The combined use of imaging approaches to assess drug release from multicomponent solid dispersions. Pharm. Res. 2017 34 5 990 1001 10.1007/s11095‑016‑2018‑x 27573574
    [Google Scholar]
  89. Hashmi A.R. Eltayib E.M. Qaisar M.N. Bafail D.A. Salimi E. Arshad S. Rubab M. Alamgeer Zahra F. Yasmeen S. Asim M.H. Mucoadhesive aprepitant-loaded nanostructured lipid carriers containing sulfhydryl surfactant for enhanced oral drug bioavailability. J. Drug Deliv. Sci. Technol. 2024 98 105904 10.1016/j.jddst.2024.105904
    [Google Scholar]
  90. Memarvar D. Yaqoubi S. Hamishehkar H. Lam M. Nokhodchi A. Impact of grinding balls on the size reduction of Aprepitant in wet ball milling procedure. Pharm. Dev. Technol. 2024 29 4 353 358 10.1080/10837450.2024.2334754 38528824
    [Google Scholar]
  91. Abouhussein D.M.N. Enhanced transdermal permeation of BCS class IV aprepitant using binary ethosome: Optimization, characterization and ex vivo permeation. J. Drug Deliv. Sci. Technol. 2021 61 102185 10.1016/j.jddst.2020.102185
    [Google Scholar]
  92. Mohammadi H.S. Asl A.H. Khajenoori M. Experimental analysis and modeling of aprepitant (an antiemetic drug for chemotherapy) solubility in subcritical water with/without co-solvent. J. Supercrit. Fluids 2024 213 106356 10.1016/j.supflu.2024.106356
    [Google Scholar]
  93. Hussain M. Rehan T. Goh K.W. Shah S.I. Khan A. Ming L.C. Shah N. Fabrication of a double core–shell particle-based magnetic nanocomposite for effective adsorption-controlled release of drugs. Polymers 2022 14 13 2681 10.3390/polym14132681 35808726
    [Google Scholar]
  94. Navari R.M. Fosaprepitant (MK-0517): A neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin. Investig. Drugs 2007 16 12 1977 1985 10.1517/13543784.16.12.1977 18042005
    [Google Scholar]
  95. Saito H. Yoshizawa H. Yoshimori K. Katakami N. Katsumata N. Kawahara M. Eguchi K. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: A multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann. Oncol. 2013 24 4 1067 1073 10.1093/annonc/mds541 23117073
    [Google Scholar]
  96. Lundberg JD Crawford BS Phillips G Berger MJ Wesolowski R Incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant. Support Care Cancer 2014 22 6 1461 1466 10.1007/s00520‑013‑2106‑y
    [Google Scholar]
  97. Leal AD Kadakia KC Looker S Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin /cyclophosphamide therapy. Support Care Cancer 2014 22 5 1313 1317 10.1007/s00520‑013‑2089‑8
    [Google Scholar]
  98. Burns D Kula J Marshall S Ashworth E Ornelas M Best Practice Approach to Successful Conversion of Fosaprepitant to Aprepitant IV in a Large Multisite Community Oncology Infusion Center: A Retrospective Analysis. Advances in Therapy 2020 37 3265 77 10.1007/s12325‑020‑01377‑z.
    [Google Scholar]
  99. Agrawal S Soni N Jain NK. Agrawal GP Solubility enhancement of poorly water-soluble celecoxib for parenteral formulations Int J Pharm Sci Res 2012 3 7 2325
    [Google Scholar]
  100. Swamy PV Sushma P Chirag G Prasad K Ali MY Raju SA Parenteral formulation of zopiclone. Int J Pharm Sci Res 2008 70 99 99 10.4103/0250‑474X.40342
    [Google Scholar]
  101. Panchal K Katke S Dash SK Gaur A Tóth B.I. Shinde A, Saha N, Mehra NK, Chaurasiya A An expanding horizon of complex injectable products: Development and regulatory considerations. Drug Deliv. Transl. Res 2023 13 2 433 72 10.1007/s13346‑022‑01223‑5
    [Google Scholar]
  102. OttoboniTLernerLSanthouseA \ Stability of Aprepitant Injectable Emulsion in Alternate Infusion Bags, in Refrigerated Storage, and Admixed with Dexamethasone and Palonosetron. Drug Des Devel Ther 2021 Jun 15 15 2519 2527 10.2147/DDDT.S282058.
    [Google Scholar]
  103. Ugwu S He X Fu Z Teng X Ji M inventors Fordoz Pharma Corp, assignee. Nanosome formulations of aprepitant and methods and applications thereof. United States patent US 11,260,028 2022 Mar 1
    [Google Scholar]
  104. Pardhi E. Tomar D.S. Khemchandani R. Srivastava V, Pawar A, Yadav R, Goud D, Godugu C, Samanthula G, Mehra NK. Enhancing solubility, bioavailability and anti-cancer efficacy of aprepitant through a naringin-based co-amorphous system. Journal of Molecular Liquids. 2025 425 127225 10.1016/j.molliq.2025.127225
    [Google Scholar]
  105. Ghahremanloo A. Asgharzadeh F. Gheybi F. Hosseini H. Hashemy S.I. Sahebkar A. Synergistic anticancer effects of liposomal doxorubicin and aprepitant combination therapy in breast cancer: Preclinical insights and therapeutic potential. Journal of Drug Delivery Science and Technology. 2025 105 106620 10.1016/j.jddst.2025.106620
    [Google Scholar]
  106. Li Y Fu R Jiang T Duan D Wu Y, Li C, Li Z, Ni R, Li L, Liu Y. Mechanism of lethal skin toxicities induced by epidermal growth factor receptor inhibitors and related treatment strategies. Frontiers in Oncology 2022 10.3389/fonc.2022.804212
    [Google Scholar]
  107. Szöllősi AG Oláh A Lisztes E Griger Z Tóth BI. Pruritus: a sensory symptom generated in cutaneous immuno-neuronal crosstalk. Frontiers in Pharmacology. 2022 13 745658 10.3389/fphar.2022.745658
    [Google Scholar]
  108. He A Alhariri JM Sweren RJ Kwatra MM Kwatra SG Aprepitant for the treatment of chronic refractory pruritus. BioMed research is international 2017 10.1155/2017/4790810
    [Google Scholar]
  109. Vincenzi B Trower M Duggal A, Guglielmini P, Harris P, Jackson D, Lacouture ME, Ratti E, Tonini G, Wood A, Ständer S. Neurokinin-1 antagonist orvepitant for EGFRI-induced pruritus in patients with cancer: a randomised, placebo-controlled phase II trial. BMJ open 2020102 e030114
    [Google Scholar]
/content/journals/raddf/10.2174/0126673878374342250708153111
Loading
Aprepitant: Review on Solubility Enhancement
Bentham Science Publishers ; https://doi.org/10.2174/0126673878374342250708153111
/content/journals/raddf/10.2174/0126673878374342250708153111
/content/journals/raddf/10.2174/0126673878374342250708153111
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: NK-1 antagonist ; solubility enhancement ; Anti-emetic ; Aprepitant ; solubility ; CINV

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