Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Amorphous Drug Solubility and Absorption Enhancement

  • Chapter
  • First Online:
Amorphous Drugs

Abstract

The poor oral bioavailability of many active pharmaceutical ingredients (APIs) resulting from low solubility is one of the important challenges in pharmaceutical technology. Over the last two decades the number of relatively insoluble drugs has grown steadily. Nowadays it is estimated that approximately 70% of new drug candidates are characterized by poor solubility. In order to ensure the optimum therapeutic efficacy, the selection of the drug substance and formulation is crucial in drug design. The development and approval of new, innovative and safe drugs is tremendously complex and requires extensive knowledge of materials, current technological processes and regulations. Bearing in mind that the form of drug should be suitable for the administration route and safe to apply, understanding of manufacturing process is of key importance to successful dosage form development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hörter D, Dressman JB (2001) Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev 46(1–3):75–87

    Article  Google Scholar 

  2. Kawabata Y, Wada K, Nakatani M et al (2011) Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm 420(1):1–10

    Article  CAS  Google Scholar 

  3. Brough C, Williams III RO (2013) Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int J Pharm 453(1):157–166

    Article  CAS  Google Scholar 

  4. DiNunzio JC, Miller DA, Yang W et al (2008) Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole. Mol Pharm 5(6):968–980

    Article  CAS  Google Scholar 

  5. Hancock BC, Parks M (2000) What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res 17(4):397–404

    Article  CAS  Google Scholar 

  6. Pastrano GL, Ghaly ES (2012) Physicochemical characterization of spray dried for mulation containing amorphous drug. Int J Pharm Pharm Sci 4(4):563–570

    Google Scholar 

  7. Vasconcelos T, Marques S, das Neves J et al (2016) Amorphous solid dispersions: rational selection of a manufacturing process. Adv Drug Deliv Rev 100:85–101

    Article  CAS  Google Scholar 

  8. Sekiguchi K, Obi N (1961) Studies on absorption of eutectic mixture. I. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Chem Pharm Bull 9(11):866–872

    Article  CAS  Google Scholar 

  9. Chiou WL, Riegelman S (1971) Pharmaceutical applications of solid dispersion systems. J Pharm Sci 60(9):1281–1302

    Article  CAS  Google Scholar 

  10. Goldberg AH, Gibaldi M, Kanig JL (1966) Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures III: experimental evaluation of griseofulvin—succinic acid solid solution. J Pharm Sci 55(5):487–492

    Article  CAS  Google Scholar 

  11. Vasconcelos T, Sarmento B, Costa P (2007) Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 12(23–24):1068–1075

    Article  CAS  Google Scholar 

  12. Vo CL-N, Park C, Lee B-J (2013) Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm 85(3 Part B):799–813

    Article  CAS  Google Scholar 

  13. Laitinen R, Priemel PA, Surwase S et al (2014) Theoretical considerations in developing amorphous solid dispersions. In: Shah N, Sandhu H, Choi DS et al (eds) Amorphous solid dispersions—theory and practice. Springer, New York

    Google Scholar 

  14. Leuner C, Dressman J (2000) Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50(1):47–60

    Article  CAS  Google Scholar 

  15. Baghel S, Cathcart H, O’Reilly NJ (2016) Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci 105(9):2527–2544

    Article  CAS  Google Scholar 

  16. Craig DQM (2002) The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 231(2):131–144

    Article  CAS  Google Scholar 

  17. Sharma A, Jain CP (2011) Solid dispersion: a promising technique to enhance solubility of poorly water soluble drug. Int J Drug Deliv 1(2):149–170

    Google Scholar 

  18. Jain S, Patel N, Lin S (2015) Solubility and dissolution enhancement strategies: current understanding and recent trends. Drug Dev Ind Pharm 41(6):875–887

    Article  CAS  Google Scholar 

  19. Alonzo DE, Zhang GGZ, Zhou D et al (2010) Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm Res 27(4):608–618

    Article  CAS  Google Scholar 

  20. Elder D, Holm R (2013) Aqueous solubility: simple predictive methods (in silico, in vitro and bio-relevant approaches). Int J Pharm 453(1):3–11

    Article  CAS  Google Scholar 

  21. Sun DD, Lee PI (2015) Haste makes waste: the interplay between dissolution and precipitation of supersaturating formulations. AAPS J 17(6):1317–1326

    Article  CAS  Google Scholar 

  22. Brouwers J, Brewster ME, Augustijns P (2009) Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J Pharm Sci 98(8):2549–2572

    Article  CAS  Google Scholar 

  23. Huang L-F, Tong W-Q (2004) Impact of solid state properties on developability assessment of drug candidates. Adv Drug Deliv Rev 56(3):321–334

    Article  CAS  Google Scholar 

  24. Lipinski CA, Lombardo F, Dominy BW et al (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64(Suppl):4–17

    Article  Google Scholar 

  25. Xie T, Taylor LS (2016) Dissolution performance of high drug loading celecoxib amorphous solid dispersions formulated with polymer combinations. Pharm Res 33(3):739–750

    Article  CAS  Google Scholar 

  26. Meng F, Trivino A, Prasad D et al (2015) Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions. Eur J Pharm Sci 71:12–24

    Article  CAS  Google Scholar 

  27. Lipinski CA, Lombardo F, Dominy BW et al (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23(1–3):3–25

    Article  CAS  Google Scholar 

  28. Butler JM, Dressman JB (2010) The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci 99(12):4940–4954

    Article  CAS  Google Scholar 

  29. Byrn SR, Henck JO (2012) Optimizing the physical form—opportunities and limitations. Drug Discov Today Technol 9(2):e73–e78

    Article  CAS  Google Scholar 

  30. Van den Mooter G (2012) The use of amorphous solid dispersions: a formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today Technol 9(2):e79–e85

    Article  Google Scholar 

  31. Dressman JB, Vertzoni M, Goumas K et al (2007) Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev 59(7):591–602

    Article  CAS  Google Scholar 

  32. Van Drooge DJ, Hinrichs WLJ, Frijlink HW (2004) Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions. J Control Release 97(3):441–452

    Article  Google Scholar 

  33. Janssens S, Van den Mooter G (2009) Review: physical chemistry of solid dispersions. J Pharm Pharmacol 61(12):1571–1586

    Article  CAS  Google Scholar 

  34. Rinaki E, Dokoumetzidis A, Macheras P (2003) The mean dissolution time depends on the dose/solubility ratio. Pharm Res 20(3):406–408

    Article  CAS  Google Scholar 

  35. Colclough N, Ruston L, Tam K (2008) Aqueous solubility in drug discovery chemistry, DMPK, biological assays. In: van de Waterbeemd H, Testa B (eds) Drug bioavailability: estimation of solubility, permeability, absorption and bioavailability. Methods and prickles in medicinal chemistry, vol 40, 2nd edn. Wiley, Hoboken, NJ, pp 10–28

    Google Scholar 

  36. Ojarinta R, Heikkinen AT, Sievänen E, Laitinen R (2017) Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: the ability of amino acids to stabilize the supersaturated state of indomethacin. Eur J Pharm Biopharm 112:85–95

    Article  CAS  Google Scholar 

  37. Xiong X, Xu K, Du Q et al (2017) Effects of temperature and solvent on the solid-state transformations of pranlukast during mechanical milling. J Pharm Sci 106(6):1680–1687. https://doi.org/10.1016/j.xphs.2017.02.020

    Article  CAS  Google Scholar 

  38. Wlodarski K, Sawicki W, Paluch KJ et al (2014) The influence of amorphization methods on the apparent solubility and dissolution rate of tadalafil. Eur J Pharm Sci 62:132–140

    Article  CAS  Google Scholar 

  39. Lepek P, Sawicki W, Wlodarski K et al (2013) Effect of amorphization method on telmisartan solubility and the tableting process. Eur J Pharm Biopharm 83:114–121

    Article  CAS  Google Scholar 

  40. Zerrouk N, Chemtob C, Arnaud P et al (2001) In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions. Int J Pharm 225:49–62

    Article  CAS  Google Scholar 

  41. Wei Q, Keck CM, Müller RH (2017) Oral hesperidin—amorphization and improved dissolution properties by controlled loading onto porous silica. Int J Pharm 518:253–263

    Article  CAS  Google Scholar 

  42. Newa M, Bhandari KH, Li DX et al (2007) Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int J Pharm 343:228–237

    Article  CAS  Google Scholar 

  43. Miller DA, McConville JT, Yang W et al (2007) Hot-melt extrusion for enhanced delivery of drug particles. J Pharm Sci 96:361–376

    Article  CAS  Google Scholar 

  44. Sugimoto I, Kuchiki A, Nakagawa H et al (1980) Dissolution and absorption of nifedipine from nifedipine–polyvinylpyrrolidone coprecipitate. Drug Dev Ind Pharm 6:137–160

    Article  CAS  Google Scholar 

  45. Costa ED, Orlandi S, Leonardi D et al (2016) Unexpected solvent impact in the crystallinity of praziquantel/poly(vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study. Int J Pharm 511:983–993

    Article  CAS  Google Scholar 

  46. Yamashita K, Nakate T, Okimoto K et al (2003) Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm 267(1–2):79–91

    Article  CAS  Google Scholar 

  47. Park J, Cho W, Cha K et al (2013) Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process. Int J Pharm 441:50–55

    Article  CAS  Google Scholar 

  48. Ferguson J, Pataki H (2013) Solvent-free melt electrospinning for preparation of fast dissolving drug delivery system and comparison with solvent-based electrospun and melt extruded systems. J Pharm Sci 102:508–517

    Article  Google Scholar 

  49. Dhumal RS, Biradar SV, Yamamura S et al (2008) Preparation of amorphous cefuroxime axetil nanoparticles by sonoprecipitation for enhancement of bioavailability. Eur J Pharm Biopharm 70:109–115

    Article  CAS  Google Scholar 

  50. Knopp MM, Chourak N, Khan F et al (2016) Effect of polymer type and drug dose on the in vitro and in vivo behavior of amorphous solid dispersions. Eur J Pharm Biopharm 105:106–114

    Article  CAS  Google Scholar 

  51. Sarode AL, Wang P, Obara S et al (2014) Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs. Eur J Pharm Biopharm 86:351–360

    Article  CAS  Google Scholar 

  52. Karavasili C, Kokove L, Kontopoulou I et al (2016) Dissolution enhancement of the poorly soluble drug nifedipine by co-spray drying with microporous zeolite beta. J Drug Deliv Sci Technol 35:91–97

    Article  CAS  Google Scholar 

  53. Zheng X, Yang R, Tang X et al (2007) Part I: Characterization of solid dispersions of nimodipine prepared by hot-melt extrusion. Drug Dev Ind Pharm 33(7):791–802

    Article  CAS  Google Scholar 

  54. Zheng X, Yang R, Zhang Y et al (2007) Part II: Bioavailability in beagle dogs of nimodipine solid dispersions prepared by hot-melt extrusion. Drug Dev Ind Pharm 33:783–789

    Article  CAS  Google Scholar 

  55. Li S, Liu Y, Liu T et al (2011) Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique. Int J Pharm 411:172–177

    Article  CAS  Google Scholar 

  56. Jensen LG, Skautrup FB, Müllertz A, Abrahamsson B, Rades T, Priemel PA (2017) Amorphous is not always better—A dissolution study on solid state forms of carbamazepine. Int J Pharm 522(1–2):74–79

    Article  CAS  Google Scholar 

  57. LaFountaine JS, Prasad LK, Miller DA et al (2017) Mucoadhesive amorphous solid dispersions for sustained release of poorly water soluble drugs. Eur J Pharm Biopharm 113:157–167

    Article  CAS  Google Scholar 

  58. Moes J, Koolen S, Huitema A et al (2013) Development of an oral solid dispersion formulation for use in low-dose metronomic chemotherapy of paclitaxel. Eur J Pharm Biopharm 83(1):87–94

    Article  CAS  Google Scholar 

  59. Otsuka M, Maeno Y, Fukami T et al (2016) Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment. Eur J Pharm Biopharm 108:25–31

    Article  CAS  Google Scholar 

  60. Galia E, Horton J, Dressman JB (1999) Albendazole generics—a comparative in vitro study. Pharm Res 16:1871–1875

    Article  CAS  Google Scholar 

  61. Onoue S, Sato H, Ogawa K et al (2010) Improved dissolution and pharmacokinetic behavior of cyclosporine A using high-energy amorphous solid dispersion approach. Int J Pharm 399:94–101

    Article  CAS  Google Scholar 

  62. Vaughn JM, McConville JT, Crisp MT et al (2006) Supersaturation produces high bioavailability of amorphous danazol particles formed by evaporative precipitation into aqueous solution and spray freezing into liquid technologies. Drug Dev Ind Pharm 32:559–567

    Article  CAS  Google Scholar 

  63. Newa M, Bhandari KH, Kim JO et al (2008) Enhancement of solubility, dissolution and bioavailability of ibuprofen in solid dispersion systems. Chem Pharm Bull 56:569–574

    Article  CAS  Google Scholar 

  64. Law D, Schmitt EA, Marsh KC et al (2004) Ritonavir—PEG 8000 amorphous solid dispersions: in vitro and in vivo evaluations. J Pharm Sci 93:563–570

    Article  CAS  Google Scholar 

  65. Mura P, Moyano JR, González-Rodríguez ML et al (2005) Characterization and dissolution properties of ketoprofen in binary and ternary solid dispersions with polyethylene glycol and surfactants. Drug Dev Ind Pharm 31(4-5):425–434

    Article  CAS  Google Scholar 

  66. Liu J, Cao F, Zhang C et al (2013) Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion. Acta Pharm Sin B 3(4):263–272

    Article  Google Scholar 

  67. Chauhan H, Kuldipkumar A, Barder T et al (2014) Correlation of inhibitory effects of polymers on indomethacin precipitation in solution and amorphous solid crystallization based on molecular interaction. Pharm Res 31(2):500–515

    Article  CAS  Google Scholar 

  68. Fule R, Paithankar V, Amin P (2016) Hot melt extrusion based solid solution approach: exploring polymer comparison, physicochemical characterization and in-vivo evaluation. Int J Pharm 499(1-2):280–294

    Article  CAS  Google Scholar 

  69. Fule R, Dhamecha D, Maniruzzaman M et al (2015) Development of hot melt co-formulated antimalarial solid dispersion system in fixed dose form (ARLUMELT): evaluating amorphous state and in vivo performance. Int J Pharm 496(1):137–156

    Article  CAS  Google Scholar 

  70. Song CK, Yoon I-S, Kim D-D (2016) Poloxamer-based solid dispersions for oral delivery of docetaxel: differential effects of F68 and P85 on oral docetaxel bioavailability. Int J Pharm 507(1-2):102–108

    Article  CAS  Google Scholar 

  71. Rashid R, Kim DW, Din FU et al (2015) Effect of hydroxypropylcellulose and Tween 80 on physicochemical properties and bioavailability of ezetimibe-loaded solid dispersion. Carbohydr Polym 130:26–31

    Article  CAS  Google Scholar 

  72. Liu H, Taylor LS, Edgar KJ (2015) The role of polymers in oral bioavailability enhancement; A review. Polymer 77:399–415

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Physics, University of Silesia, Chorzów, Poland

    Marzena Rams-Baron & Marian Paluch

  2. Chair of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University - Medical College, Kraków, Poland

    Renata Jachowicz & Witold Jamroz

  3. Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk State University, Novosibirsk, Russian Federation

    Elena Boldyreva

  4. AbbVie, North Chicago, USA

    Deliang Zhou

Authors
  1. Marzena Rams-Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renata Jachowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elena Boldyreva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deliang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Witold Jamroz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marian Paluch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rams-Baron, M., Jachowicz, R., Boldyreva, E., Zhou, D., Jamroz, W., Paluch, M. (2018). Amorphous Drug Solubility and Absorption Enhancement. In: Amorphous Drugs. Springer, Cham. https://doi.org/10.1007/978-3-319-72002-9_3

Download citation

Publish with us

Policies and ethics

Search

Navigation