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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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
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
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
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
Hancock BC, Parks M (2000) What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res 17(4):397–404
Pastrano GL, Ghaly ES (2012) Physicochemical characterization of spray dried for mulation containing amorphous drug. Int J Pharm Pharm Sci 4(4):563–570
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
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
Chiou WL, Riegelman S (1971) Pharmaceutical applications of solid dispersion systems. J Pharm Sci 60(9):1281–1302
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
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
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
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
Leuner C, Dressman J (2000) Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50(1):47–60
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
Craig DQM (2002) The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 231(2):131–144
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
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
Alonzo DE, Zhang GGZ, Zhou D et al (2010) Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm Res 27(4):608–618
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
Sun DD, Lee PI (2015) Haste makes waste: the interplay between dissolution and precipitation of supersaturating formulations. AAPS J 17(6):1317–1326
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
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
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
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
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
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
Butler JM, Dressman JB (2010) The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci 99(12):4940–4954
Byrn SR, Henck JO (2012) Optimizing the physical form—opportunities and limitations. Drug Discov Today Technol 9(2):e73–e78
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
Dressman JB, Vertzoni M, Goumas K et al (2007) Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev 59(7):591–602
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
Janssens S, Van den Mooter G (2009) Review: physical chemistry of solid dispersions. J Pharm Pharmacol 61(12):1571–1586
Rinaki E, Dokoumetzidis A, Macheras P (2003) The mean dissolution time depends on the dose/solubility ratio. Pharm Res 20(3):406–408
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
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
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
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
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
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
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
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
Miller DA, McConville JT, Yang W et al (2007) Hot-melt extrusion for enhanced delivery of drug particles. J Pharm Sci 96:361–376
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Galia E, Horton J, Dressman JB (1999) Albendazole generics—a comparative in vitro study. Pharm Res 16:1871–1875
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
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
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
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
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
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
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
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
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
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
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
Liu H, Taylor LS, Edgar KJ (2015) The role of polymers in oral bioavailability enhancement; A review. Polymer 77:399–415
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
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
DOI: https://doi.org/10.1007/978-3-319-72002-9_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-72001-2
Online ISBN: 978-3-319-72002-9
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)