Supersaturating drug delivery systems: The answer to solubility-limited oral bioavailability?

Journal of Pharmaceutical Sciences

Volumn 98, Issue 8, 2009, Pages 2549-2572

  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

Apparent solubility; Dissolution; Equilibrium solubility; Gastrointestinal; Intestinal absorption; Intraluminal drug concentrations; Oral drug delivery; Precipitation inhibition; Supersaturation

Indexed keywords

ALBENDAZOLE; AMPRENAVIR; AMPRENAVIR PHOSPHATE; ATAZANAVIR; CARBOMER; CARBOPOL 974P; CELECOXIB; CYCLODEXTRIN DERIVATIVE; DANAZOL; DIPYRIDAMOLE; DODECYL SULFATE SODIUM; EUDRAGIT; FELODIPINE; FLIBANSERIN; FOSPHENYTOIN SODIUM; HYDROXYPROPYLCELLULOSE; HYDROXYPROPYLMETHYLCELLULOSE; ITRACONAZOLE; LANSOPRAZOLE; LEFRADAFIBAN; MACROGOL 6000; PACLITAXEL; PHENYTOIN; POLOXAMER; POLYVINYL ALCOHOL; POVIDONE; SILICON DIOXIDE; SURFACTANT; TACROLIMUS; TOCOFERSOLAN; UNINDEXED DRUG;

AREA UNDER THE CURVE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM; DRUG FORMULATION; DRUG MEGADOSE; DRUG SCREENING; DRUG SOLUBILITY; DRUG STABILITY; DRUG TRANSPORT; GASTROINTESTINAL TRACT FUNCTION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTESTINE ABSORPTION; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRECIPITATION; REVIEW; SOLUBILIZATION; SUPERSATURATING DRUG DELIVERY SYSTEM;

EID: 68249128120     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.21650     Document Type: Review

References (105)

1. Amidon GL, Lennernäs H, Shah VP, Crison JR. 1995. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12:413-420.
2. Lipinski CA. 2000. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44:235-249.
3. Wenlock MC, Austin RP, Barton P, Davis AM, Leeson PD. 2003. A comparison of physiochemical property profiles of development and marketed oral drugs. J Med Chem 46:1250-1256. (Pubitemid 36428230)
4. Gribbon P, Sewing A. 2005. High-throughput drug discovery: What can we expect from HTS? Drug Discov Today 10:17-22.
5. 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)
6. Higuchi T. 1960. Physical chemical analysis of percutaneous absorption process from creams and ointments. J Soc Cosmet Chem 11:85-97.
7. Guzmán H, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P, Mustonen P, Gardner C, Chen H, Moreau J, Almarsson O, Remenar J. 2004. A "spring and parachute" approach to designing solid celecoxib formulations having enhanced oral absorption. AAPS J 6:Abstract T2189.
8. Guzmán HR, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P, Gardner CR, Chen H, Moreau J, Almarsson O, Remenar JF. 2007. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J Pharm Sci 96:2686-2702. (Pubitemid 47597818)
9. Mosharraf M, Sebhatu T, Nyström C. 1999. The effects of disordered structure on the solubility and dissolution rates of some hydrophilic, sparingly soluble drugs. Int J Pharm 177:29-51. (Pubitemid 29067426)
10. Watanabe T, Hasegawa S, Wakiyama N, Kusai A, Senna M. 2002. Prediction of apparent equilibrium solubility of indomethacin compounded with silica by 13C solid state NMR. Int J Pharm 248:123-129. (Pubitemid 35341416)
11. Vertzoni M, Dressman J, Butler J, Hempenstall J, Reppas C. 2005. Simulation of fasting gastric conditions and its importance for the in vivo dissolution of lipophilic compounds. Eur J Pharm Biopharm 60:413-417. (Pubitemid 40922839)
12. Jantratid E, Janssen N, Reppas C, Dressman JB. 2008. Dissolution media simulating conditions in the proximal human gastrointestinal tract: An update. Pharm Res 25:1663-1676.
13. Dressman JB, Amidon GL, Reppas C, Shah VP. 1998. Dissolution testing as a prognostic tool for oral drug absorption: Immediate release dosage forms. Pharm Res 15:11-22. (Pubitemid 28080861)
14. Matteucci ME, Brettmann BK, Rogers TL, Elder EJ, Williams R III, Johnston KP. 2007. Design of potent amorphous drug nanoparticles for rapid generation of highly supersaturated media. Mol Pharm 4:782-793.
15. Overhoff KA, McConville JT, Yang W, Johnston KP, Peters JI, Williams R III. 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.
16. Strickley RG. 2004. Solubilizing excipients in oral and injectable formulations. Pharm Res 21:201-230.
17. Strickley RG, Oliyai R. 2007. Solubilizing vehicles for oral formulation development. In: Augustijns P, Brewster ME, editors. Solvent systems and their selection in pharmaceutics and biopharmaceutics. New York: AAPS Press and Springer. pp. 257-308.
18. Pouton CW. 2000. Lipid formulations for oral administration of drugs: Non-emulsifying, selfemulsifying and 'self-microemulsifying' drug delivery systems. Eur J Pharm Sci 11:S93-S98.
19. Pouton CW. 2006. Formulation of poorly watersoluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 29:278-287.
20. Hauss DJ. 2007. Oral lipid-based formulations. Adv Drug Deliv Rev 59:667-676.
21. O'Driscoll CM, Griffin BT. 2008. Biopharmaceutical challenges associated with drugs with low aqueous solubility-the potential impact of lipid-based formulations. Adv Drug Deliv Rev 60:617-624.
22. Narang AS, Delmarre D, Gao D. 2007. Stable drug encapsulation in micelles and microemulsions. Int J Pharm 345:9-25. (Pubitemid 350103649)
23. Pouton CW, Porter CJH. 2008. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Adv Drug Deliv Rev 60:625-637.
24. Martin A, Wu PL, Adjei A, Lindstrom RE, Elworthy PH. 1982. Extended hildebrand solubility approach and the log linear solubility equation. J Pharm Sci 71:849-856.
25. Brewster ME, Mackie C, Lampo A, Noppe M, Loftsson T. 2007. The use of solubilizing excipients and approaches to generate toxicology vehicles for contemporary drug pipelines. In: Augustijns P, Brewster ME, editors. Solvent systems and their selection in pharmaceutics and biopharmaceutics. New York: AAPS Press and Springer. pp. 221-256.
26. Poelma FG, Breäs R, Tukker JJ, Crommelin DJ. 1991. Intestinal absorption of drugs. The influence of mixed micelles on the disappearance kinetics of drugs from the small intestine of the rat. J Pharm Pharmacol 43:317-324.
27. Chiu Y, Higaki K, Neudeck BL, Barnett JL, Welage LS, Amidon GL. 2003. Human jejunal permeability of cyclosporin A: Influence of surfactants on P-glycoprotein efflux in Caco-2 cells. Pharm Res 20:749-756. (Pubitemid 36515307)
28. Gao P, Rush BD, Pfund WP, Huang T, Bauer JM, Morozowich W, Kuo M, Hageman MJ. 2003. Development of a supersaturable SEDDS (SSEDDS) formulation of paclitaxel with improved oral bioavailability. J Pharm Sci 92:2386-2398. (Pubitemid 37484765)
29. Gao P, Morozowich W. 2006. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Deliv 3:97-110. (Pubitemid 43056394)
30. Gao P, Guyton ME, Huang T, Bauer JM, Stefanski KJ, Lu Q. 2004. Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations. Drug Dev Ind Pharm 30:221-229. (Pubitemid 38420267)
31. Gao P, Akrami A, Alvarez F, Hu J, Li L, Ma C, Surapaneni S. in press. Characterization and optimization of AMG 517 supersaturatable self-emulsifying drug delivery system (S-SEDDS) for improved oral absorption. J Pharm Sci. DOI: 10.1002/jps.21451.
32. Appel L, Babcock W, Friesen DT, Ray RJ, Shamblin S, Shanker R, Smithey D. 2006. Pharmaceutical dosage forms comprising a low-solubility drug and a polymer. Patent WO 2006/024944 A2.
33. Miller DA, McConville JT, Yang W, Williams R III, McGinity JW. 2007. Hot-melt extrusion for enhanced delivery of drug particles. J Pharm Sci 96:361-376. (Pubitemid 46363567)
34. Higuchi WI, Bernardo PD, Mehta SC. 1967. Polymorphism and drug availability. II. Dissolution rate behavior of the polymorphic forms of sulfathiazole and methylprednisolone. J Pharm Sci 56:200-207.
35. Hancock BC, Parks M. 2000. What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res 17:397-404.
36. Blagden N, de Matas M, Gavan PT, York P. 2007. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 59:617-630. (Pubitemid 47285407)
37. Keck CM, Müller RH. 2006. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm 62:3-16.
38. Kipp JE. 2004. The role of solid nanoparticle technology in the parenteral delivery of poorly watersoluble drugs. Int J Pharm 284:109-122.
39. Simonelli AP, Mehta SC, Higuchi WI. 1970. Inhibition of sulfathiazole crystal growth by polyvinylpyrrolidone. J Pharm Sci 59:633-638.
40. Serajuddin AT. . Solid dispersion of poorly watersoluble drugs: Early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 88:1058-1066.
41. Leuner C, Dressman J. 2000. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50:47-60. (Pubitemid 30326688)
42. Vasconcelos T, Sarmento B, Costa P. 2007. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discovery Today 12:1068-1075. (Pubitemid 350186132)
43. Craig DQM. 2002. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 231:131-144.
44. Urbanetz NA, Lippold BC. 2005. Solid dispersions of nimodipine and polyethylene glycol 2000: Dissolution properties and physico-chemical characterisation. Eur J Pharm Biopharm 59:107-118. (Pubitemid 39573442)
45. Brewster ME, Vandecruys R, Peeters J, Neeskens P, Verreck G, Loftsson T. 2008. Comparative interaction of 2-hydroxypropyl-beta-cyclodextrin and sulfobutylether-beta-cyclodextrin with itraconazole: Phase-solubility behavior and stabilization of supersaturated drug solutions. Eur J Pharm Sci 34:94-103.
46. Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, Higaki K, Kimura T. 2003. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm 267:79-91. (Pubitemid 37352952)
47. Vogt M, Vertzoni M, Kunath K, Reppas C, Dressman JB. 2008. Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug, in dogs. Eur J Pharm Biopharm 68:338-345.
48. Vogt M, Kunath K, Dressman JB. 2008. Dissolution improvement of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur J Pharm Biopharm 68:330-337.
49. Salonen J, Laitinen L, Kaukonen AM, Tuura J, Björkqvist M, Heikkilä T, Vähä-Heikkilä K, Hirvonen J, Lehto V. 2005. Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs. J Control Release 108:362-374. (Pubitemid 41608668)
50. Kaukonen AM, Laitinen L, Salonen J, Tuura J, Heikkilä T, Limnell T, Hirvonen J, Lehto V. 2007. Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles. Eur J Pharm Biopharm 66:348-356. (Pubitemid 46756223)
51. Mellaerts R, Aerts CA, Van Humbeeck J, Augustijns P, Van den Mooter G, Martens JA. 2007. Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials. Chem Commun 13:1375-1377. (Pubitemid 46465984)
52. Mellaerts R, Mols R, Kayaert P, Annaert P, Van Humbeeck J, Van den Mooter G, Martens JA, 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.
53. Mellaerts R, Mols R, Jammaer JAG, Aerts CA, Annaert P, Van Humbeeck J, Van den Mooter G, Augustijns P, Martens JA. 2008. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica. Eur J Pharm Biopharm 69:223-230.
54. Stella VJ, Nti-Addae KW. 2007. Prodrug strategies to overcome poor water solubility. Adv Drug Deliv Rev 59:677-694.
55. Heimbach T, Oh DM, Li LY, Rodríguez-Hornedo N, Garcia G, Fleisher D. 2003. Enzyme-mediated precipitation of parent drugs from their phosphate prodrugs. Int J Pharm 261:81-92. (Pubitemid 36962747)
56. Brouwers J, Tack J, Augustijns P. 2007. In vitro behavior of a phosphate ester prodrug of amprenavir in human intestinal fluids and in the Caco-2 system: Illustration of intraluminal supersaturation. Int J Pharm 336:302-309.
57. Heimbach T, Oh D, Li LY, Forsberg M, Savolainen J, Leppänen J, Matsunaga Y, Flynn G, Fleisher D. 2003. Absorption rate limit considerations for oral phosphate prodrugs. Pharm Res 20:848-856. (Pubitemid 36628429)
58. Kostewicz ES, Wunderlich M, Brauns U, Becker R, Bock T, Dressman JB. 2004. Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J Pharm Pharmacol 56:43-51. (Pubitemid 38195327)
59. Zhuang H, Mao C. 2006. Understanding of polymers on enhancing solution concentration of poorly soluble drugs in supersaturated systems. AAPS J 8:Abstract W4228.
60. Tomilo DL, Smith PF, Ogundele AB, Difrancesco R, Berenson CS, Eberhardt E, Bednarczyk E, Morse GD. 2006. Inhibition of atazanavir oral absorption by lansoprazole gastric acid suppression in healthy volunteers. Pharmacotherapy 26: 341-346. (Pubitemid 43334673)
61. Lim SG, Sawyerr AM, Hudson M, Sercombe J, Pounder RE. 1993. Short report: The absorption of fluconazole and itraconazole under conditions of low intragastric acidity. Aliment Pharmacol Ther 7:317-321. (Pubitemid 23198307)
62. Willems L, van der Geest R, de Beule K. 2001. Itraconazole oral solution and intravenous formulations: A review of pharmacokinetics and pharmacodynamics. J Clin Pharm Ther 26:159-169. (Pubitemid 32592545)
63. Six K, Daems T, de Hoon J, Van Hecken A, Depre M, Bouche M, Prinsen P, Verreck G, Peeters J, Brewster ME, Van den Mooter G. 2005. Clinical study of solid dispersions of itraconazole prepared by hotstage extrusion. Eur J Pharm Sci 24:179-186. (Pubitemid 40127548)
64. Miller DA, DiNunzio JC, Yang W, McGinity JW, Williams R III. 2008. Enhanced in vivo absorption of itraconazole via stabilization of supersaturation following acidic-to-neutral pH transition. Drug Dev Ind Pharm 34:890-902.
65. Miller DA, DiNunzio JC, Yang W, McGinity JW, Williams R III. 2008. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption. Pharm Res 25:1450-1459.
66. Kashchiev D, van Rosmalen GM. 2003. Review: Nucleation in solutions revisited. Cryst Res Technol 38:555-574.
67. Rodríguez-Hornedo N, Murphy D. 1999. Significance of controlling crystallization mechanisms and kinetics in pharmaceutical systems. J Pharm Sci 88:651-660. (Pubitemid 29325991)
68. Miller J, Rodriguez-Hornedo N, Blackburn A, Macikenas D, Collman B. 2007. Solvent systems for crystallization and polymorph selection. In: Augustijns P, Brewster M, editors. Solvent systems and their selection in pharmaceutics and biopharmaceutics. New York: Springer and AAPS Press. pp. 53-110.
69. 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.
70. Raghavan SL, Schuessel K, Davis A, Hadgraft J. 2003. Formation and stabilisation of triclosan colloidal suspensions using supersaturated systems. Int J Pharm 261:153-158. (Pubitemid 36962753)
71. Overhoff KA, Moreno A, Miller DA, Johnston KP, Williams R III. 2007. Solid dispersions of itraconazole and enteric polymers made by ultra-rapid freezing. Int J Pharm 336:122-132. (Pubitemid 46551563)
72. Raghavan SL, Trividic A, Davis AF, Hadgraft J. 2001. Crystallization of hydrocortisone acetate: Influence of polymers. Int J Pharm 212:213-221. (Pubitemid 32119447)
73. Yokoi Y, Yonemochi E, Terada K. 2005. Effects of sugar ester and hydroxypropyl methylcellulose on the physicochemical stability of amorphous cefditoren pivoxil in aqueous suspension. Int J Pharm 290:91-99. (Pubitemid 40139048)
74. Sekikawa H, Fujiwara J, Naganuma T, Nakano M, Arita T. 1978. Dissolution behaviors and gastrointestinal absorption of phenytoin in phenytoin- polyvinylpyrrolidone coprecipitate. Chem Pharm Bull 26:3033-3039. (Pubitemid 9050291)
75. Suzuki H, Sunada H. 1998. Influence of watersoluble polymers on the dissolution of nifedipine solid dispersions with combined carriers. Chem Pharm Bull 46:482-487. (Pubitemid 28188567)
76. 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)
77. Terayama H, Inada K, Nakayama H, Yasueda S, Esumi K. 2004. Preparation of stable aqueous suspension of a hydrophobic drug with polymers. Colloids Surf B Biointerfaces 39:159-164. (Pubitemid 39536238)
78. Raghavan SL, Kiepfer B, Davis AF, Kazarian SG, Hadgraft J. 2001. Membrane transport of hydrocortisone acetate from supersaturated solutions; the role of polymers. Int J Pharm 221:95-105. (Pubitemid 32524039)
79. Rangel-Yagui CO, Pessoa AJ, Tavares LC. 2005. Micellar solubilization of drugs. J Pharm Pharm Sci 8:147-165.
80. Loftsson T, Másson M, Brewster ME. 2004. Selfassociation of cyclodextrins and cyclodextrin complexes. J Pharm Sci 93:1091-1099.
81. Brewster ME, Loftsson T. 2007. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 59:645-666.
82. Torres-Labandeira JJ, Davignon P, Pitha J. 1991. Oversaturated solutions of drug in hydroxypropylcyclodextrins: Parenteral preparation of pancratistatin. J Pharm Sci 80:384-386.
83. Uekama K, Ikegami K, Wang Z, Horiuchi Y, Hirayama F. 1992. Inhibitory effect of 2-hydroxypropyl- beta-cyclodextrin on crystal-growth of nifedipine during storage: Superior dissolution and oral bioavailability compared with polyvinylpyrrolidone K-30. J Pharm Pharmacol 44:73-78.
84. Iervolino M, Raghavan SL, Hadgraft J. 2000. Membrane penetration enhancement of ibuprofen using supersaturation. Int J Pharm 198:229-238. (Pubitemid 30184859)
85. Xiang T, Anderson BD. 2002. Stable supersaturated aqueous solutions of silatecan 7-t-butyldimethylsilyl- 10-hydroxycamptothecin via chemical conversion in the presence of a chemically modified beta-cyclodextrin. Pharm Res 19:1215-1222. (Pubitemid 34985007)
86. Dias MMR, Raghavan SL, Pellett MA, Hadgraft J. 2003. The effect of beta-cyclodextrins on the permeation of diclofenac from supersaturated solutions. Int J Pharm 263:173-181. (Pubitemid 37087944)
87. Loftsson T, Vogensen SB, Brewster ME, Konrádsdóttir F. 2007. Effects of cyclodextrins on drug delivery through biological membranes. J Pharm Sci 96:2532-2546.
88. Vandecruys R, Peeters J, Verreck G, Brewster ME. 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)
89. Brewster ME, 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.
90. Janssens S, Nagels S, Armas HND, D'Autry W, Van Schepdael A, Van den Mooter G. 2008. Formulation and characterization of ternary solid dispersions made up of Itraconazole and two excipients, TPGS 1000 and PVPVA 64, that were selected based on a supersaturation screening study. Eur J Pharm Biopharm 69:158-166.
91. Dai W, Dong LC, Shi X, Nguyen J, Evans J, Xu Y, Creasey AA. 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)
92. Brewster ME, Neeskens P, Peeters J. 2007. Solubilization of itraconazole as a function of cyclodextrin structural space. J Incl Phenom Macro Chem 57:561-566.
93. Brouwers J, Tack J, Lammert F, Augustijns P. 2006. Intraluminal drug and formulation behavior and integration in in vitro permeability estimation: A case study with amprenavir. J Pharm Sci 95:372-383. (Pubitemid 43241979)
94. Brouwers J, Tack J, Augustijns P. 2007. Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state. Pharm Res 24:1862-1869. (Pubitemid 47389240)
95. Dressman JB, Vertzoni M, Goumas K, Reppas C. 2007. Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev 59:591-602. (Pubitemid 47287780)
96. Clarysse S, Psachoulias D, Tack J, Reppas C, Augustijns P. 2007. Postprandial changes in solubilizing properties of human intestinal fluids. AAPS J 9:Abstract T3150.
97. Gu C, Rao D, Gandhi RB, 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)
98. Dressman JB, Thelen K, Jantratid E. 2008. Towards quantitative prediction of oral drug absorption. Clin Pharmacokinet 47:655-667.
99. Megrab NA, Williams AC, Barry BW. 1995. Oestradiol permeation through human skin and silastic membrane: Effects of propylene glycol and supersaturation. J Contr Release 36:277-294.
100. Moser K, Kriwet K, Froehlich C, Kalia YN, Guy RH. 2001. Supersaturation: Enhancement of skin penetration and permeation of a lipophilic drug. Pharm Res 18:1006-1011. (Pubitemid 32799947)
101. Hou H, Siegel RA. 2006. Enhanced permeation of diazepam through artificial membranes from supersaturated solutions. J Pharm Sci 95:896-905.
102. Kohri N, Yamayoshi Y, Xin H, Iseki K, Sato N, Todo S, Miyazaki K. 1999. Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique. J Pharm Pharmacol 51:159-164. (Pubitemid 29131308)
103. Wire MB, Shelton MJ, Studenberg S. 2006. Fosamprenavir: Clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 45:137-168. (Pubitemid 43290828)
104. Vaughn JM, McConville JT, Crisp MT, Johnston KP, Williams R III. 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.
105. Gilis P, De Condé V, Vandecruys R. 1999. Pellets having a core coated with an antifungal and a polymer. Patent WO 00/03697.