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Review Article

Aqueous solubility of crystalline and amorphous drugs: Challenges in measurement

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Pages 187-200 | Received 12 Aug 2009, Accepted 12 Mar 2010, Published online: 30 Apr 2010

References

  • Grant DJW, Higuchi T. Solubility behavior of organic compounds. New York: John Wiley & Sons; 1990.
  • Yalkowski SH, Banerjee S. Aqueous solubility: Methods of estimation for organic compounds. New York: Marcel Dekker; 1992.
  • Higuchi T, Mei FL, Kimura STJ, Rytting H. Solubility determination of barely aqueous-soluble organic solids. J Pharmaceut Sci 1979;68(10):1267–1272.
  • Vippagunta SR, Brittain HG, Grant DJW. Crystalline solids. Adv Drug Deliv Rev 2001;48(1):3–26.
  • Threlfall TL. Analysis of organic polymorphs: A review. Analyst 1995;120:2435–2460.
  • Yalkowski SH. Solubility and solubilization in aqueous media. Washington, DC: Oxford University Press; 1999.
  • Grant DJW, Higuchi T. Solubility behaviour of organic compounds. New York: Wiley; 1990.
  • Singhal D, Curatolo W. Drug polymorphism and dosage form design: A practical perspective. Adv Drug Deliv Rev 2004;56(3):335–347.
  • Pudipeddi M, Serajuddin ATM. Trends in solubility of polymorphs. J Pharmaceut Sci 2005;94(5):929–939.
  • Carlton RA. Experimental methods in the study of thermodynamic polymorph stability relationships. Am Pharmaceut Rev 2006;9(1):88,90–93,99.
  • Cruz Cabeza AJ, Day GM, Motherwell WDS, Jones W. Amide pyramidalization in carbamazepine: A flexibility problem in crystal structure prediction? Crystal Growth Des 2006;6(8):1858–1866.
  • Day GM, Van de Streek J, Bonnet A, Burley JC, Jones W, Motherwell WDS. Polymorphism of scyllo-inositol: Joining crystal structure prediction with experiment to elucidate the structures of two polymorphs. Crystal Growth Des 2006;6(10):2301–2307.
  • Brittain HG. Spectral methods for the characterization of polymorphs and solvates. J Pharmaceut Sci 1997;86(4):405–412.
  • Giron D. Monitoring polymorphism of drugs, an on-going challenge. Part 1. Am Pharmaceut Rev 2008;11(1):66–71.
  • Giron D. Monitoring polymorphism of drugs, an on-going challenge. Part 2. Am Pharmaceut Rev 2008;11(3):86–90.
  • Shah B, Kakumanu VK, Bansal AK. Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharmaceut Sci 2006;95(8):1641–1665.
  • Bahl D, Bogner R. Amorphization of indomethacin by co-grinding with Neusilin US2: Amorphization kinetics, physical stability and mechanism. Pharmaceut Res 2006;23(10):2317–2325.
  • Huttenrauch R. Molecular galenics as the basis of modern drug formation. Acta Pharmaceut Technol 1978;6:55–127.
  • Corrigan OI, Holohan EM, Sabra K. Amorphous forms of thiazide diuretics prepared by spray drying. Int J Pharmaceut 1984;18:195–200.
  • Sheen PC, Kim SI, Petillo JJ, Serajuddin ATM. Bioavailability of a poorly water-soluble drug from tablet and solid dispersion in humans. J Pharmaceut Sci 1991;80:712–714.
  • Pozzi F, Longo A, Lazzarini C, Carenzi A. Formulations of ubidecarenone with improved bioavailability. Eur J Pharmaceut Biopharmaceut 1991;37:243–246.
  • Sheen PC, Khetarpal VK, Cariola CM, Rowlings CE. Formulation studies of a poorly water-soluble drug in solid dispersions to improve bioavailability. Int J Pharmaceut 1995;18:221–227.
  • Grantscharova E, Gutzow I. Vapour pressure, solubility and affinity of undercooled melts and glasses. J Non-Crystalline Solids 1986;81:99–127.
  • Hancock BC. Disordered drug delivery: Destiny, dynamics and the Deborah number. J Pharm Pharmacol 2002;54:737–746.
  • Shamblin SL, Tang X, Chang L, Hancock BC, Pikal MJ. Characterization of the time scales of molecular motion in pharmaceutically important glasses. J Phys Chem B 1999;103(20):4113–4121.
  • Kawakami K, Miyoshi K, Ida Y. Impact of the amount of excess solids on apparent solubility. Pharmaceut Res 2005;22(9):1537–1543.
  • Elamin AA, Ahlneck C, Alderborn G, Nystrom C. Increased metastable solubility of milled griseofulvin, depending on the formation of a disordered surface structure. Int J Pharmaceut 1994;111:159–170.
  • Bevan CD, Lloyd RS. A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. Anal Chem 2000;72(8):1781–1787.
  • Kerns EH, Di L, Carter GT. In vitro solubility assays in drug discovery. Curr Drug Metabol 2008;9:879–885.
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46(1–3):3–26.
  • Betigeri S, Thakur A, Shukla R, Raghavan K. Effect of polymer additives on the transformation of BMS-566394 anhydrate to the dihydrate form. Pharmaceut Res 2008;25(5):1043–1051.
  • Brewster ME, Vandecruys R, Peeters J, Neeskens P, Verreck G, Loftsson T. Comparative interaction of 2-hydroxypropyl-[beta]-cyclodextrin and sulfobutylether-[beta]-cyclodextrin with itraconazole: Phase-solubility behavior and stabilization of supersaturated drug solutions. Eur J Pharmaceut Sci 2008;34(2–3):94–103.
  • Thomas S, Brightman F, Gill H, Lee S, Pufong B. Simulation modelling of human intestinal absorption using Caco-2 permeability and kinetic solubility data for early drug discovery. J Pharmaceut Sci 2008;97(10):4557–4574.
  • Mosharraf M, Sebhatu T, Nystrom C. The effects of disordered structure on the solubility and dissolution rates of some hydrophilic, sparingly soluble drugs. Int J Pharmaceut 1999;177(1):29–51.
  • Watanabe T, Hasegawa S, Wakiyama N, Kusai A, Senna M. Prediction of apparent equilibrium solubility of indomethacin compounded with silica by 13C solid state NMR. Int J Pharmaceut 2002;248(1–2):123–129.
  • Weiner N. In: Pharmaceutical dosage forms – disperse systems. New York: Marcel Dekker, Inc; 1996.
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23(1–3):3–25.
  • Bahl D, Bogner R. 2008. Amorphization alone does not account for the enhancement of solubility of drug co-ground with silicate: The case of indomethacin. AAPS PharmSciTech 9(1):146–153.
  • Stuart M, Box K. Chasing equilibrium: Measuring the intrinsic solubility of weak acids and bases. Analyt Chem 2005;77:983–990.
  • Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instr 1965;4:117–212.
  • Glomme A, Marz J, Dressman JB. Comparison of a miniaturized shake-flask solubility method with automated potentiometric acid/base titrations and calculated solubilities. J Pharmaceut Sci 2005;94(1):1–16.
  • Avdeef A. pH-metric solubility. 1: Solubility-pH profiles from Bjerrum plots. Gibbs buffer and pKa in the solid state. Pharm Pharmacol Communic 1998;4:165–178.
  • Avdeef A, Berger CM. pH-metric solubility. 3: Dissolution titration template method for solubility determination. Eur J Pharmaceut Sci 2001;14(4):281–291.
  • Avdeef A, Berger CM, Brownell C. pH-metric solubility. 2: Correlation between the acid-base titration and the saturation shake-flask solubility-pH methods. Pharmaceut Res 2000;17(1):85–89.
  • Avdeef A. Physicochemical profiling (solubility, permeability and charge state). Curr Top Med Chem 2001;1:277–351.
  • Wood JH, Syarto JE, Letterman H. Improved holder for intrinsic dissolution rate studies. J Pharmaceut Sci 1965;54(7):1068.
  • Venkatesh S, Li J, Xu Y, Vishnuvajjala R, Anderson BD. Intrinsic solubility estimation and pH-solubility behavior of Cosalane (NSC 658586), an extremely hydrophobic diprotic acid. Pharmaceut Res 1996;13(10):1453–1459.
  • Yu LX, Carlin AS, Amidon GL, Hussain AS. Feasibility studies of utilizing disk intrinsic dissolution rate to classify drugs. Int J Pharmaceut 2003;270:221–227.
  • Mooney KG, Mintun MA, Himmelstein KJ, Stella VJ. Dissolution kinetics of carboxylic acids I: Effect of pH under unbuffered conditions. J Pharmaceut Sci 1981;70:13–22.
  • McNamara DP, Amidon GL. Dissolution of acidic and basic compounds from the rotating disk: Influence of convective diffusion and reaction. J Pharmaceut Sci 1986;75(9):858–868.
  • McNamara DP, Amidon GL. Reaction plane approach for estimating the effects of buffers on the dissolution rate of acidic drugs. J Pharmaceut Sci 1988;77(6):511–517.
  • Stella VJ, Mooney KG, Pipkin JD. Dissolution and ionization of warfarin. J Pharmaceut Sci 1984;73(7):946–948.
  • Mooney KG, Rodriguez-gaxiola M, Mintun M, Himmelstein KJ, Stella VJ. Dissolution kinetics of phenylbutazone. J Pharmaceut Sci 1981;70(12):1358–1365.
  • Box KJ, Völgyi G, Baka E, Stuart M, Takács-Novák K, Comer JEA. Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution – a validation study. J Pharmaceut Sci 2006;95(6):1298–1307.
  • Kibbey CE, Poole SK, Robinson B, Jackson JD, Durham D. An integrated process for measuring the physicochemical properties of drug candidates in a preclinical discovery environment. J Pharmaceut Sci 2001;90(8):1164–1175.
  • Dinter C, Schuetz A, Blume T, Weinmann H, Harre M, Neh H. Automated solubility determination using a customized robotic system and a turbidity probe. J Assoc Lab Automat 2005;10(6):408–411.
  • Kerns EH. High throughput physicochemical profiling for drug discovery. J Pharmaceut Sci 2001;90(11):1838–1858.
  • Avdeef A. High throughput measurements of solubility profiles. In: Testa B, van de Waterbeend H., Folkers G, Guy R, editors. Pharmacokinetic optimization in drug research; biological, physicochemical, and computational strategies. Weinheim: Verlag Helvetica Chimica Acta: Zurich and Wiley–VCH; 2001:305–326.
  • Seadeek C, Ando H, Bhattachar SN, Heimbach T, Sonnenberg JL, Blackburn AC. Automated approach to couple solubility with final pH and crystallinity for pharmaceutical discovery compounds. J Pharmaceut Biomed Anal 2007;43(5):1660–1666.
  • Dehring KA, Workman HL, Miller KD, Mandagere A, Poole SK. Automated robotic liquid handling/laser-based nephelometry system for high throughput measurement of kinetic aqueous solubility. J Pharmaceut Biomedical Anal 2004;36(3):447–456.
  • Sugano K, Kato T, Suzuki K, Keiko K, Sujaku T, Mano T. High throughput solubility measurement with automated polarized light microscopy analysis. J Pharmaceuti Sci 2006;95(10):2115–2122.
  • Wyttenbach N, Alsenz J, Grassmann O. Miniaturized assay for solubility and residual solid screening (SORESOS) in early drug development. Pharmaceut Res 2007;24(5):888–898.
  • Vandecruys R, Peeters J, Verreck G, Brewster ME. Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design. Int J Pharmaceut 2007;342:168–175.
  • Raghavan SL, Trividic A, Davis AF, Hadgraft J. Effect of cellulose polymers on supersaturation and in vitro membrane transport of hydrocortisone acetate. Int J Pharmaceut 2000;193(2):231–237.
  • Brewster ME, Vandecruys R, Verreck G, Peeters J. Supersaturating drug delivery systems: Effect of hydrophilic cyclodextrins and other excipient on the formation and stabilization of supersaturated drug solutions. Pharmazie 2008;63:217–220.
  • Yi Y, Hatziavramidis D, Myerson AS, Waldo M, Beylin VG, Mustakis J. Development of a small-scale automated solubility measurement apparatus. Industrial Engineer Chem Res 2005;44(15):5427–5433.
  • Wang Z, Burrell LS, Lambert WJ. Solubility of E2050 at various pH: A case in which apparent solubility is affected by the amount of excess solid. J Pharmaceut Sci 2002;91(6):1445–1455.
  • ACD, Labs. ACD pKa database. 8.00 ed., 90 Adelaide Street, West Toronto, M5H3V9, Canada: Advanced Chemistry Development Inc.
  • Chen J, Brooks CL, Scheraga HA. Revisiting the carboxylic acid dimers in aqueous solution: Interplay of hydrogen bonding, hydrophobic interactions, and entropy. J Phys Chem B 2008;112(2):242–249.
  • Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharmaceut Res 1997;14(12):1691–1698.
  • Baka E, Comer JEA, Takács-Novák K. Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J Pharmaceut Biomed Anal 2008; 46:335–341.
  • Mosharraf M, Nystrom C. Apparent solubility of drugs in partially crystalline systems. Drug Develop Industrial Pharm 2003;29(6):603–622.
  • Gupta P, Chawla G, Bansal AK. Physical stability and solubility advantage from amorphous celecoxib: The role of thermodynamic quantities and molecular mobility. Mol Pharmaceut 2004;1(6):406–413.
  • Chawla G, Bansal AK. A comparative assessment of solubility advantage from glassy and crystalline forms of a water-insoluble drug. Eur J Pharmaceut Sci 2007;32(1):45–57.
  • Chiou WL. Pharmaceutical applications of solid dispersion systems: X-ray diffraction and aqueous solubility studies on griseofulvin-polyethylene glycol 6000 systems. J Pharmaceut Sci 1977;66(7):989–991.
  • Sekiguchi K, Obi N. Absorption of eutectic mixtures. I. A comparison of the behavior of a eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Chem Pharm Bull 1961;9:866–872.
  • Ford JL. The current status of solid dispersions. Pharm Acta Helv 1986;61(3):69–88.
  • Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 2007;12(23–24):1068–1075.
  • Ruan L-P Yu, B-Y, Fu G-M Zhu, D-N. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharmaceut Biomed Anal 2005;38(3):457–464.
  • Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharmaceut Biopharmaceut 2000;50(1):47–60.
  • Serajuddin ATM. Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs. J Pharmaceut Sci 1999;88(10):1058–1066.
  • Damian F, Blaton N, Kinget R, Van den Mooter G. Physical stability of solid dispersions of the antiviral agent UC-781 with PEG 6000, Gelucire 44/14 and PVP K30. Int J Pharmaceut 2002;244:87–98.
  • Yokoi Y, Yonemochi E, Terada K. Changes in surface properties by granulation and physicochemical stability of granulated amorphous cefditoren pivoxil with additives. Int J Pharmaceut 2004;280:67–75.
  • Ambike AA, Mahadik KR, Paradkar A. Stability study of amorphous valdecoxib. Int J Pharmaceut 2004;282(1–2):151–162.
  • Watanabe T, Wakiyama N, Usui F, Ikeda M, Isobe T, Senna M. Stability of amorphous indomethacin compounded with silica. Int J Pharmaceut 2001;226:81–91.
  • Gupta MK, Tseng Y-C Goldman, D, Bogner RH. Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules. Pharmaceut Res 2002;19(11):1663–1672.
  • Li J, Guo Y, Zografi G. The solid-state stability of amorphous quinapril in the presence of beta-cyclodextrins. J Pharmaceut Sci 2002;91:229–243.
  • Loftsson T, Fririksdóttir H, Gumundsdóttir TK. The effect of water-soluble polymers on aqueous solubility of drugs. Int J Pharmaceut 1996;127(2):293–296.
  • Usui F, Maeda K, Kusai A, Nishimura K, Keiji Y. Inhibitory effects of water-soluble polymers on precipitation of RS-8359. Int J Pharmaceuti 1997;154(1):59–66.
  • Hancock BC, Parks M. What is the true solubility advantage for amorphous pharmaceuticals? Pharmaceut Res 2000;17(4):397–404.
  • Gupta P, Kakumanu VK, Bansal AK. Stability and solubility of Celecoxib-PVP amorphous dispersions: A molecular perspective. Pharmaceut Res 2004;21(10):1762–1769.

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