Evaluation of gastrointestinal drug supersaturation and precipitation: Strategies and issues

International Journal of Pharmaceutics

Volumn 453, Issue 1, 2013, Pages 25-35

  Bevernage, Jan ^a   Brouwers, Joachim ^a   Brewster, Marcus E ^b   Augustijns, Patrick ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^b JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

Intestinal absorption; Precipitation; Supersaturation

Indexed keywords

GASTROINTESTINAL AGENT; ITRACONAZOLE; LIPID;

CRYSTALLIZATION; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG SCREENING; DRUG SOLUBILITY; DRUG SOLUTION; GROWTH INHIBITION; HUMAN; HYDRODYNAMICS; IN VITRO STUDY; INTESTINE ABSORPTION; NONHUMAN; PH; PRECIPITATION; PRIORITY JOURNAL; REVIEW; SUPERSATURATING DRUG DELIVERY SYSTEM; TEMPERATURE;

EID: 84884128650     PISSN: 03785173     EISSN: 18733476     Source Type: Journal    
DOI: 10.1016/j.ijpharm.2012.11.026     Document Type: Review

References (77)

1. Alonzo, D.E., Zhang, G.G.Z., Zhou, D., Gao, Y., Taylor, L.S., 2010. Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm. Res. 27, 608-618.
2. Anby, M.U., Williams, H.D., McIntosh, M., Benameur, H., Edwards, G.A., Pouton, C.W., Porter, C.J.H., 2012. 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.
3. Arnold, Y.E., Imanidis, G., Kuentz, M.T., 2011. Advancing in-vitro drug precipitation testing: new process monitoring tools and a kinetic nucleation and growth model. J. Pharm. Pharmacol. 63, 333-341.
4. Augustijns, P., Brewster, M.E., 2012. Supersaturating drug delivery systems: fast is not necessarily good enough. J. Pharm. Sci. 101, 7-9.
5. Baldyga, J., Orciuch, W., 2001. Some hydrodynamic aspects of precipitation. Powder Technol. 121, 9-19. (Pubitemid 33034619)
6. Beig, A., Miller, J.M., Dahan, A., 2012. Accounting for the solubility-permeability interplay in oral formulation development for poor water solubility drugs: the effect of PEG-400 on carbamazepine absorption. Eur. J. Pharm. Biopharm. 81, 386-391.
7. Bevernage, J., Brouwers, J., Clarysse, S., Vertzoni, M., Tack, J., Annaert, P., Augustijns, P., 2010. Drug supersaturation in simulated and human intestinal fluids representing different nutritional states. J. Pharm. Sci. 99, 4525-4534.
8. Bevernage, J., Forier, T., Brouwers, J., Tack, J., Annaert, P., Augustijns, P., 2011. Excipient-mediated supersaturation stabilization in human intestinal fluids. Mol. Pharm. 8, 564-570.
9. Bevernage, J., Brouwers, J., Annaert, P., Augustijns, P., 2012a. Drug precipitation-permeation interplay: supersaturation in an absorptive environment. Eur. J. Pharm. Biopharm. 82, 424-428.
10. Bevernage, J., Hens, B., Brouwers, J., Tack, J., Annaert, P., Augustijns, P., 2012b. Supersaturation in human gastric fluids. Eur. J. Pharm. Biopharm. 81, 184-189.
11. Box, K.J., Völgyi, G., Baka, E., Stuart, M., Takács- Novák, K., Comer, J.E.A., 2006. Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution-a validation study. J. Pharm. Sci. 95, 1298-1307. (Pubitemid 43874443)
12. Box, K., Comer, J.E., Gravestock, T., Stuart, M., 2009. New ideas about the solubility of drugs. Chem. Biodivers. 6, 1767-1788.
13. Brewster, M.E., Vandecruys, R., Verreck, G., Peeters, J., 2008. Supersaturating drug delivery systems: effect of hydrophilic cyclodextrins and other excipients on the formation and stabilization of supersaturated drug solutions. Pharmazie 63, 217-220. (Pubitemid 351449932)
14. Brouwers, J., Augustijns, P., 2012. Biorelevant evaluation of supersaturation and precipitation: do we understand the gastrointestinal environment? Bull. Tech. Gattefosse 104, 69-80.
15. Brouwers, J., Brewster, M.E., Augustijns, P., 2009. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J. Pharm. Sci. 98, 2549-2572.
16. Carlert, S., Pålsson, A., Hanisch, G., von Corswant, C., Nilsson, C., Lindfors, L., Lennernäs, H., Abrahamsson, B., 2010. Predicting intestinal precipitation-a case example for a basic BCS class II drug. Pharm. Res. 27, 2119-2130.
17. Chandran, S., Gesenberg, C., Levons, J., Hubert, M., Raghavan, K., 2011. A high-throughput spectrophotometric approach for evaluation of precipitation resistance. J. Pharm. Biomed. Anal. 56, 698-704.
18. Curatolo, W., Nightingale, J.A., Herbig, S.M., 2009. Utility of hydroxypropylmethyl-cellulose acetate succinate (HPMCAS) for initiation and maintenance of drug supersaturation in the GI milieu. Pharm. Res. 26, 1419-1431.
19. D'Arcy, D.M., Healy, A.M., Corrigan, O.I., 2009. Towards determining appropriate hydrodynamic conditions for in vitro in vivo correlations using computational fluid dynamics. Eur. J. Pharm. Sci. 37, 291-299.
20. Dahan, A., Miller, J.M., Hoffman, A., Amidon, G.E., Amidon, G.L., 2010. The solubility-permeability interplay in using cyclodextrins as pharmaceutical solubilizers: mechanistic modeling and application to progesterone. J. Pharm. Sci. 99, 2739-2749.
21. Dai, W., Dong, L.C., Shi, X., Nguyen, J., Evans, J., Xu, Y., Creasey, A.A., 2007. Evaluation of drug precipitation of solubility-enhancing liquid formulations using milligram quantities of a new molecular entity (NME). J. Pharm. Sci. 96, 2957-2969. (Pubitemid 350221196)
22. Dalvi, S.V., Dave, R.N., 2010. Analysis of nucleation kinetics of poorly water-soluble drugs in presence of ultrasound and hydroxypropyl methyl cellulose during antisolvent precipitation. Int. J. Pharm. 387, 172-179.
23. DiNunzio, J.C., Miller, D.A., Yang, W., McGinity, J.W., Williams, R.O., 2008. Amorphous compositions using concentration enhancing polymers for improved bioavailability of itraconazole. Mol. Pharm. 5, 968-980.
24. DiNunzio, J.C., Brough, C., Miller, D.A., Williams 3rd, R.O., McGinity, J.W., 2010. Applications of KinetiSol dispersing for the production of plasticizer free amorphous solid dispersions. Eur. J. Pharm. Sci. 40, 179-187.
25. Dong, W.Y., Maincent, P., Bodmeier, R., 2007. In vitro and in vivo evaluation of carbamazepine-loaded enteric microparticles. Int. J. Pharm. 331, 84-92. (Pubitemid 46176503)
26. Dressman, J.B., Amidon, G.L., Reppas, C., Shah, V.P., 1998. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm. Res. 15, 11-22. (Pubitemid 28080861)
27. Fatouros, D.G., Nielsen, F.S., Douroumis, D., Hadjileontiadis, L.J., Mullertz, A., 2008. In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks. Eur. J. Pharm. Biopharm. 69, 887-898.
28. Friesen, D.T., Shanker, R., Crew, M., Smithey, D.T., Curatolo, W.J., Nightingale, J.A.S., 2008. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol. Pharm. 5, 1003-1019.
29. Gao, P., Shi, Y., 2012. Characterization of supersaturatable formulations for improved absorption of poorly soluble drugs. AAPS J. 14, 703-713.
30. Gu, C.-H., Rao, D., Gandhi, R.B., Hilden, J., Raghavan, K., 2005. Using a novel multicompartment dissolution system to predict the effect of gastric pH on the oral absorption of weak bases with poor intrinsic solubility. J. Pharm. Sci. 94, 199-208. (Pubitemid 40116383)
31. Hsieh, Y.-L., Ilevbare, G., Van Eerdenbrugh, B., Box, K., Sanchez-Felix, M., Taylor, L., 2012. pH-induced precipitation behavior of weakly basic compounds determination of extent and duration of supersaturation using potentiometric titration and correlation to solid state properties. Pharm. Res. 29, 2738-2753.
32. Jantratid, E., Janssen, N., Reppas, C., Dressman, J.B., 2008. Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm. Res. 25, 1663-1676.
33. Kataoka, M., Sugano, K., da Costa Mathews, C., Wong, J.W., Jones, K.L., Masaoka, Y., Sakuma, S., Yamashita, S., 2012. Application of dissolution/permeation system for evaluation of formulation effect on oral absorption of poorly water-soluble drugs in drug development. Pharm. Res. 29, 1485-1494.
34. Kohli, K., Chopra, S., Dhar, D., Arora, S., Khar, R.K., 2010. Self-emulsifying drug delivery systems: an approach to enhance oral bioavailability. Drug Discov. Today 15, 958-965.
35. Kostewicz, E.S., Wunderlich, M., Brauns, U., Becker, R., Bock, T., Dressman, J.B., 2004. Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J. Pharm. Pharmacol. 56, 43-51. (Pubitemid 38195327)
36. Kuentz, M., 2012. Lipid-based formulations for oral delivery of lipophilic drugs. Drug Discov. Today: Technol. 9, e97-e104.
37. Larsen, A.T., Sassene, P., Müllertz, A., 2011. In vitro lipolysis models as a tool for the characterization of oral lipid and surfactant based drug delivery systems. Int. J. Pharm. 417, 245-255.
38. Lehto, P., Aaltonen, J., Tenho, M., Rantanen, J., Hirvonen, J., Tanninen, V.P., Peltonen, L., 2009. Solvent-mediated solid phase transformations of carbamazepine: effects of simulated intestinal fluid and fasted state simulated intestinal fluid. J. Pharm. Sci. 98, 985-996.
39. Li, P., Vishnuvajjala, R., Tabibi, S.E., Yalkowsky, S.H., 1998. Evaluation of in vitro precipitation methods. J. Pharm. Sci. 87, 196-199. (Pubitemid 28081328)
40. Lindfors, L., Forssén, S., Westergren, J., Olsson, U., 2008. Nucleation and crystal growth in supersaturated solutions of a model drug. J. Colloid Interface Sci. 325, 404-413.
41. Lipinski, C.A., 2000. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44, 235-249. (Pubitemid 32239479)
42. Llinàs, A., Goodman, J.M., 2008. Polymorph control: past, present and future. Drug Discov. Today 13, 198-210.
43. Manth, T., Mignon, D., Offermann, H., 1996. Experimental investigation of precipitation reactions under homogeneous mixing conditions. Chem. Eng. Sci. 51, 2571-2576. (Pubitemid 126660806)
44. McAllister, M., 2010. Dynamic dissolution: a step closer to predictive dissolution testing? Mol. Pharm. 7, 1374-1387.
45. Mellaerts, R., Mols, R., Kayaert, P., Annaert, P., Van Humbeeck, J., Van den Mooter, G., Martens, J.A., Augustijns, P., 2008. Ordered mesoporous silica induces pH-independent supersaturation of the basic low solubility compound itraconazole resulting in enhanced transepithelial transport. Int. J. Pharm. 357, 169-179.
46. Mellaerts, R., Aerts, A., Caremans, T.P., Vermant, J., Van den Mooter, G., Martens, J.A., Augustijns, P., 2010. Growth of itraconazole nanofibers in supersaturated simulated intestinal fluid. Mol. Pharm. 7, 905-913.
47. Miller, D.A., McConville, J.T., Yang, W., Williams, R.O., McGinity, J.W., 2007. Hot-melt extrusion for enhanced delivery of drug particles. J. Pharm. Sci. 96, 361-376. (Pubitemid 46363567)
48. Miller, D.A., DiNunzio, J.C., Yang, W., McGinity, J.W., Williams 3rd, R.O., 2008a. Enhanced in vivo absorption of itraconazole via stabilization of supersaturation following acidic-to-neutral pH transition. Drug Dev. Ind. Pharm. 34, 890-902.
49. Miller, D.A., DiNunzio, J.C., Yang, W., McGinity, J.W., Williams 3rd, R.O., 2008b. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption. Pharm. Res. 25, 1450-1459.
50. Miller, J.M., Beig, A., Carr, R.A., Spence, J.K., Dahan, A., 2012. A win-win solution in oral delivery of lipophilic drugs: supersaturation via amorphous solid dispersions increases apparent solubility without sacrifice of intestinal membrane permeability. Mol. Pharm. 9, 2009-2016.
51. Mohsin, K., Long, M.A., Pouton, C.W., 2009. Design of lipid-based formulations for oral administration of poorly water-soluble drugs: precipitation of drug after dispersion of formulations in aqueous solution. J. Pharm. Sci. 98, 3582-3595.
52. Overhoff, K.A., McConville, J.T., Yang, W., Johnston, K.P., Peters, J.I., Williams 3rd, R.O., 2008. Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing. Pharm. Res. 25, 167-175.
53. Ozaki, S., Minamisono, T., Yamashita, T., Kato, T., Kushida, I., 2012. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms. J. Pharm. Sci. 101, 214-222.
54. Porter, C.J.H., Kaukonen, A.M., Boyd, B.J., Edwards, G.A., Charman, W.N., 2004. 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. (Pubitemid 39149655)
55. Porter, C.J.H., Anby, M.U., Warren, D.B., Williams, H.D., Benameur, H., Pouton, C.W., 2011. Lipid based formulations: exploring the link between in vitro supersaturation and in vivo exposure. Bull. Tech. Gattefosse 104, 61-69.
56. Psachoulias, D., Vertzoni, M., Goumas, K., Kalioras, V., Beato, S., Butler, J., Reppas, C., 2011. Precipitation in and supersaturation of contents of the upper small intestine after administration of two weak bases to fasted adults. Pharm. Res. 28, 3145-3158.
57. Psachoulias, D., Vertzoni, M., Butler, J., Busby, D., Symillides, M., Dressman, J., Reppas, C., 2012. An in vitro methodology for forecasting luminal concentrations and precipitation of highly permeable lipophilic weak bases in the fasted upper small intestine. Pharm. Res. 29, 3486-3498.
58. Raghavan, S.L., Trividic, A., Davis, A.F., Hadgraft, J., 2001. Crystallization of hydrocortisone acetate: influence of polymers. Int. J. Pharm. 212, 213-221. (Pubitemid 32119447)
59. Rodríguez-Hornedo, N., Murphy, D., 1999. Significance of controlling crystallization mechanisms and kinetics in pharmaceutical systems. J. Pharm. Sci. 88, 651-660. (Pubitemid 29325991)
60. Sassene, P.J., Knopp, M.M., Hesselkilde, J.Z., Koradia, V., Larsen, A., Rades, T., Müllertz, A., 2010. Precipitation of a poorly soluble model drug during in vitro lipolysis: characterization and dissolution of the precipitate. J. Pharm. Sci. 99, 4982-4991.
61. Shanbhag, A., Rabel, S., Nauka, E., Casadevall, G., Shivanand, P., Eichenbaum, G., Mansky, P., 2008. Method for screening of solid dispersion formulations of low-solubility compounds-miniaturization and automation of solvent casting and dissolution testing. Int. J. Pharm. 351, 209-218. (Pubitemid 351186860)
62. Shi, Y., Gao, P., Gong, Y., Ping, H., 2010. Application of a biphasic test for characterization of in vitro drug release of immediate release formulations of celecoxib and its relevance to in vivo absorption. Mol. Pharm. 7, 1458-1465.
63. Shono, Y., Jantratid, E., Dressman, J.B., 2011. Precipitation in the small intestine may play a more important role in the in vivo performance of poorly soluble weak bases in the fasted state: case example nelfinavir. Eur. J. Pharm. Biopharm. 79, 349-356.
64. Singhal, D., Curatolo, W., 2004. Drug polymorphism and dosage form design: a practical perspective. Adv. Drug Deliv. Rev. 56, 335-347. (Pubitemid 38201429)
65. Stegemann, S., Leveiller, F., Franchi, D., de Jong, H., Lindén, H., 2007. When poor solubility becomes an issue: from early stage to proof of concept. Eur. J. Pharm. Sci. 31, 249-261. (Pubitemid 47079001)
66. Stuart, M., Box, K., 2005. Chasing equilibrium: measuring the intrinsic solubility of weak acids and bases. Anal. Chem. 77, 983-990. (Pubitemid 40261763)
67. Takano, R., Takata, N., Saito, R., Furumoto, K., Higo, S., Hayashi, Y., Machida, M., Aso, Y., Yamashita, S., 2010. Quantitative analysis of the effect of supersaturation on in vivo drug absorption. Mol. Pharm. 7, 1431-1440.
68. Usui, F., Maeda, K., Kusai, A., Nishimura, K., Yamamoto, K., 1997. Inhibitory effects of water-soluble polymers on precipitation of RS-8359. Int. J. Pharm. 154, 59-66. (Pubitemid 27326820)
69. Van Speybroeck, M., Mellaerts, R., Mols, R., Thi, T.D., Martens, J.A., Van Humbeeck, J., Annaert, P., Van den Mooter, G., Augustijns, P., 2010a. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. Eur. J. Pharm. Sci. 41, 623-630.
70. Van Speybroeck, M., Mols, R., Mellaerts, R., Thi, T.D., Martens, J.A., Humbeeck, J.V., Annaert, P., Mooter, G.V., den Augustijns, P., 2010b. Combined use of ordered mesoporous silica and precipitation inhibitors for improved oral absorption of the poorly soluble weak base itraconazole. Eur. J. Pharm. Biopharm. 75, 354-365.
71. Vandecruys, R., Peeters, J., Verreck, G., Brewster, M.E., 2007. 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. Pharm. 342, 168-175. (Pubitemid 47259339)
72. Vertzoni, M., Pastelli, E., Psachoulias, D., Kalantzi, L., Reppas, C., 2007. Estimation of intragastric solubility of drugs: in what medium? Pharm. Res. 24, 909-917. (Pubitemid 46675392)
73. Warren, D.B., Benameur, H., Porter, C.J.H., Pouton, C.W., 2010. Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: a mechanistic basis for utility. J. Drug Target. 18, 704-731.
74. Williams, H.D., Sassene, P., Kleberg, K., Bakala-N'goma, J.-C., Calderone, M., Jannin, V., Igonin, A., Partheil, A., Marchaud, D., Jule, E., Vertommen, J., Maio, M., Blundell, R., Benameur, H., Carrière, F., Müllertz, A., Porter, C.J.H., Pouton, C.W., 2012. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations. J. Pharm. Sci. 101, 3360-3380.
75. Wu, H., Khan, M.A., 2011. Quality-by-design: an integrated process analytical technology approach to determine the nucleation and growth mechanisms during a dynamic pharmaceutical coprecipitation process. J. Pharm. Sci. 100, 1969-1986.
76. Yamashita, T., Kokubo, T., Zhao, C., Ohki, Y., 2010. Antiprecipitant screening system for basic model compounds using bio-relevant media. J. Assoc. Lab. Automat. 15, 306-312.
77. Yamashita, T., Ozaki, S., Kushida, I., 2011. Solvent shift method for anti-precipitant screening of poorly soluble drugs using biorelevant medium and dimethyl sulfoxide. Int. J. Pharm. 419, 170-174.