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

Molecular Pharmaceutics

Volumn 9, Issue 7, 2012, Pages 2063-2079

  Anby, Mette U ^a   Williams, Hywel D ^a   McIntosh, Michelle ^a   Benameur, Hassan ^b   Edwards, Glenn A ^c   Pouton, Colin W ^a   Porter, Christopher J H ^a  

^a MONASH UNIVERSITY   (Australia)

^b CAPSUGEL   (France)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

bioavailability; hydroxypropyl methylcellulose (HPMC); in vitro digestion; lipid based drug delivery systems; polymeric precipitation inhibitors; poorly water soluble drugs; self emulsifying drug delivery systems (SEDDS); supersaturation

Indexed keywords

ALCOHOL; CREMOPHOR; DANAZOL; LIPID; MEDIUM CHAIN LIPID; POLYMERIC PRECIPITATION INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; DISPERSION; DRUG DELIVERY SYSTEM; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PHYSICAL PARAMETERS; PRECIPITATION; PRIORITY JOURNAL; SELF EMULSIFYING DRUG DELIVERY SYSTEM; SOLUBILIZATION; SUPERSATURATION;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DANAZOL; DOGS; DRUG DELIVERY SYSTEMS; EMULSIONS; GASTROINTESTINAL TRACT; INTESTINAL ABSORPTION; LIPIDS; MALE; POLYMERS; SOLUBILITY; SOLVENTS; SURFACE-ACTIVE AGENTS;

EID: 84863301039     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp300164u     Document Type: Article

References (65)

1. Strickley, R. G. Solubilizing Excipients in Oral and Injectable Formulations Pharm. Res. 2004, 21 (2) 201-230
2. Porter, C. J. H.; Trevaskis, N. L.; Charman, W. N. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs Nat. Rev. Drug Discovery 2007, 6 (3) 231-248
3. Patton, J. S.; Carey, M. C. Watching fat digestion Science 1979, 204 (4389) 145-148
4. Staggers, J. E.; Hernell, O.; Stafford, R. J.; Carey, M. C. Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 1. Phase behavior and aggregation states of model lipid systems patterned after aqueous duodenal contents of healthy adult human beings Biochemistry 1990, 29 (8) 2028-2040
5. Carey, M. C.; Small, D. M. The characteristics of mixed micellar solutions with particular reference to bile Am. J. Med. 1970, 49 (5) 590-608
6. Fatouros, D. G.; Bergenstahl, B.; Mullertz, A. Morphological observations on a lipid-based drug delivery system during in vitro digestion Eur. J. Pharm. Sci. 2007, 31 (2) 85-94
7. Kossena, G. A.; Charman, W. N.; Boyd, B. J.; Porter, C. J. H. Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug J. Pharm. Sci. 2005, 94 (3) 481
8. Hofmann, A. F.; Borgström, B. The Intraluminal Phase of Fat Digestion in Man: The Lipid Content of the Micellar and Oil Phases of Intestinal Content Obtained during Fat Digestion and Absorption J. Clin. Invest. 1964, 43 (2) 247-257
9. MacGregor, K. J.; Embleton, J. K.; Lacy, J. E.; Perry, E. A.; Solomon, L. J.; Seager, H.; Pouton, C. W. Influence of lipolysis on drug absorption from the gastro-intestinal tract Adv. Drug Delivery Rev. 1997, 25 (1) 33-46
10. Müllertz, A.; Fatouros, D. G.; Smith, J. R.; Vertzoni, M.; Reppas, C. Insights into Intermediate Phases of Human Intestinal Fluids Visualized by Atomic Force Microscopy and Cryo-Transmission Electron Microscopy ex Vivo Mol. Pharmaceutics 2012, 9 (2) 237-247
11. Fatouros, D.; Deen, G.; Arleth, L.; Bergenstahl, B.; Nielsen, F.; Pedersen, J.; Mullertz, A. Structural Development of Self Nano Emulsifying Drug Delivery Systems (SNEDDS) During In Vitro Lipid Digestion Monitored by Small-angle X-ray Scattering Pharm. Res. 2007, 24 (10) 1844-1853
12. Carey, M. C.; Small, D. M.; Bliss, C. M. Lipid Digestion and Absorption Annu. Rev. Physiol. 1983, 45 (1) 651-677
13. Gibson, L. Lipid-Based Excipients for Oral Drug Delivery. In Oral Lipid-Based Formulations: Enhancing the bioavailbility of poorly water-soluble drugs Hauss, D. J., Ed.; Informa Heathcare: New York, 2007; Vol. 170, pp 33-62.
14. Schick, M. J. E. Nonionic surfactants; Marcel Dekker, Inc.: New York, 1977; Vol. 1.
15. Kaukonen, A.; Boyd, B. J.; Porter, C. J. H.; Charman, W. N. Drug Solubilization Behavior During in Vitro Digestion of Simple Triglyceride Lipid Solution Formulations Pharm. Res. 2004, 21 (2) 245-253
16. Kaukonen, A.; Boyd, B. J.; Charman, W. N.; Porter, C. J. H. Drug Solubilization Behavior During in Vitro Digestion of Suspension Formulations of Poorly Water-Soluble Drugs in Triglyceride Lipids Pharm. Res. 2004, 21 (2) 254-260
17. Larsen, A. T.; Sassene, P.; Müllertz, A. In vitro lipolysis models as a tool for the characterization of oral lipid and surfactant based drug delivery systems Int. J. Pharm. 2011, 417 (1-2) 245-255
18. Porter, C. J. H.; Kaukonen, A. M.; Boyd, B. J.; Edwards, G. A.; Charman, W. N. Susceptibility to Lipase-Mediated Digestion Reduces the Oral Bioavailability of Danazol After Administration as a Medium-Chain Lipid-Based Microemulsion Formulation Pharm. Res. 2004, 21 (8) 1405-1412
19. Porter, C. J. H.; Kaukonen, A. M.; Taillardat-Bertschinger, A.; Boyd, B. J.; O'Connor, J. M.; Edwards, G. A.; Charman, W. N. Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: Studies with halofantrine J. Pharm. Sci. 2004, 93 (5) 1110-1121
20. Porter, C. J. H.; Anby, M. U.; Warren, D.; Williams, H. D.; Benameur, H.; Pouton, C. W. Lipid based formulations: Exploring the link between in vitro Supersaturation and in vivo exposure Bull. Tech. Gattefosse 2011, 104, 61-69
21. Gao, P.; Akrami, A.; Alvarez, F.; Hu, J.; Li, L.; Ma, C.; Surapaneni, S. Characterization and optimization of AMG 517 supersaturatable self-emulsifying drug delivery system (S-SEDDS) for improved oral absorption J. Pharm. Sci. 2009, 98 (2) 516-528
22. Gao, P.; Guyton, M. E.; Huang, T.; Bauer, J. M.; Stefanski, K. J.; Lu, Q. Enhanced Oral Bioavailability of a Poorly Water Soluble Drug PNU-91325 by Supersaturatable Formulations Drug Dev. Ind. Pharm. 2004, 30 (2) 221-229
23. Gao, P.; Rush, B. D.; Pfund, W. P.; Huang, T.; Bauer, J. M.; Morozowich, W.; Kuo, M.-S.; Hageman, M. J. Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability J. Pharm. Sci. 2003, 92 (12) 2386-2398
24. Gao, P.; Morozowich, W. Design and Development of Supersaturatable Self-Emulsifying Drug Delivery Systems for Enhancing the Gastrointestinal Absorption of Poorly Soluble Drugs. In Oral Lipid-Based Formulations: Enhancing the bioavailbility of poorly water-soluble drugs, 1 st ed.; Hauss, D. J., Ed.; Informa Healthcare: New York, 2007; Vol. 170, pp 303-328.
25. Miller, D.; DiNunzio, J.; Yang, W.; McGinity, J.; Williams, R. Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption Pharm. Res. 2008, 25 (6) 1450-1459
26. Raghavan, S. L.; Kiepfer, B.; Davis, A. F.; Kazarian, S. G.; Hadgraft, J. Membrane transport of hydrocortisone acetate from supersaturated solutions; the role of polymers Int. J. Pharm. 2001, 221 (1-2) 95-105
27. Simonelli, A. P.; Mehta, S. C.; Higuchi, W. I. Inhibition of sulfathiazole crystal growth by polyvinylpyrrolidone J. Pharm. Sci. 1970, 59 (5) 633-638
28. Guzmán, H. R.; Tawa, M.; Zhang, Z.; Ratanabanangkoon, P.; Shaw, P.; Gardner, C. R.; Chen, H.; Moreau, J.-P.; Almarsson, Ö.; Remenar, J. F. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations J. Pharm. Sci. 2007, 96 (10) 2686-2702
29. Vasconcelos, T.; Sarmento, B.; Costa, P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs Drug Discovery Today 2007, 12 (23-24) 1068-1075
30. Yamashita, K.; Nakate, T.; Okimoto, K.; Ohike, A.; Tokunaga, Y.; Ibuki, R.; Higaki, K.; Kimura, T. Establishment of new preparation method for solid dispersion formulation of tacrolimus Int. J. Pharm. 2003, 267 (1-2) 79-91
31. Raghavan, S. L.; Trividic, A.; Davis, A. F.; Hadgraft, J. Effect of cellulose polymers on supersaturation and in vitro membrane transport of hydrocortisone acetate Int. J. Pharm. 2000, 193 (2) 231-237
32. Cuiné, J. F.; Charman, W. N.; Pouton, C. W.; Edwards, G. A.; Porter, C. J. H. Increasing the Proportional Content of Surfactant (Cremophor EL) Relative to Lipid in Self-emulsifying Lipid-based Formulations of Danazol Reduces Oral Bioavailability in Beagle Dogs Pharm. Res. 2007, 24 (4) 748-757
33. Erlich, L.; Yu, D.; Pallister, D. A.; Levinson, R. S.; Gole, D. G.; Wilkinson, P. A.; Erlich, R. E.; Reeve, L. E.; Viegas, T. X. Relative bioavailability of danazol in dogs from liquid-filled hard gelatin capsules Int. J. Pharm. 1999, 179 (1) 49-53
34. Bakatselou, V.; Oppenheim, R. C.; Dressman, J. B. Solubilization and Wetting Effects of Bile Salts on the Dissolution of Steroids Pharm. Res. 1991, 8 (12) 1461-1469
35. Kossena, G. A.; Charman, W. N.; Boyd, B. J.; Dunstan, D. E.; Porter, C. J. H. Probing drug solubilization patterns in the gastrointestinal tract after administration of lipid-based delivery systems: A phase diagram approach J. Pharm. Sci. 2004, 93 (2) 332-348
36. Pouton, C. W. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems Eur. J. Pharm. Sci. 2000, 11 (Suppl. 2) S93-S98
37. Pouton, C. W. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system Eur. J. Pharm. Sci. 2006, 29 (3-4) 278-287
38. Sek, L.; Porter, C. J. H.; Charman, W. N. Characterisation and quantification of medium chain and long chain triglycerides and their in vitro digestion products, by HPTLC coupled with in situ densitometric analysis J. Pharm. Biomed. Anal. 2001, 25 (3-4) 651-661
39. Armand, M.; Borel, P.; Pasquier, B.; Dubois, C.; Senft, M.; Andre, M.; Peyrot, J.; Salducci, J.; Lairon, D. Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum Am. J. Physiol. 1996, 271 (1) G172-G183
40. Lindahl, A.; Ungell, A.-L.; Knutson, L.; Lennernäs, H. Characterization of Fluids from the Stomach and Proximal Jejunum in Men and Women Pharm. Res. 1997, 14 (4) 497-502
41. Pedersen, B. L.; Brøndsted, H.; Lennernäs, H.; Christensen, F. N.; Müllertz, A.; Kristensen, H. G. Dissolution of Hydrocortisone in Human and Simulated Intestinal Fluids Pharm. Res. 2000, 17 (2) 183-189
42. Brouwers, J.; Tack, J.; Lammert, F.; Augustijns, P. Intraluminal drug and formulation behavior and integration in in vitro permeability estimation: A case study with amprenavir J. Pharm. Sci. 2006, 95 (2) 372-383
43. Bevernage, J.; Brouwers, J.; Clarysse, S.; Vertzoni, M.; Tack, J.; Annaert, P.; Augustijns, P. Drug supersaturation in simulated and human intestinal fluids representing different nutritional states J. Pharm. Sci. 2010, 99 (11) 4525-4534
44. Moreno, M. P. d. l. C.; Oth, M.; Deferme, S.; Lammert, F.; Tack, J.; Dressman, J.; Augustijns, P. Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum J. Pharm. Pharmacol. 2006, 58 (8) 1079-1089
45. Persson, E.; Löfgren, L.; Hansson, G.; Abrahamsson, B.; Lennernäs, H.; Nilsson, R. Simultaneous assessment of lipid classes and bile acids in human intestinal fluid by solid-phase extraction and HPLC methods J. Lipid Res. 2007, 48 (1) 242-251
46. Reymond, J.-P.; Sucker, H.; Vonderscher, J. In Vivo Model for Ciclosporin Intestinal Absorption in Lipid Vehicles Pharm. Res. 1988, 5 (10) 677-679
47. Khoo, S.-M.; Humberstone, A. J.; Porter, C. J. H.; Edwards, G. A.; Charman, W. N. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine Int. J. Pharm. 1998, 167 (1-2) 155-164
48. Martin, A.; Wu, P. L.; Adjei, A.; Lindstrom, R. E.; Elworthy, P. H. Extended hildebrand solubility approach and the log linear solubility equation J. Pharm. Sci. 1982, 71 (8) 849-856
49. Mattson, F. H.; Volpenhein, R. A. The Digestion and Absorption of Triglycerides J. Biol. Chem. 1964, 239 (9) 2772-2777
50. Porter, C. J. H.; Pouton, C. W.; Cuine, J. F.; Charman, W. N. Enhancing intestinal drug solubilisation using lipid-based delivery systems Adv. Drug Delivery Rev. 2008, 60 (6) 673-691
51. Dahan, A.; Hoffman, A. The effect of different lipid based formulations on the oral absorption of lipophilic drugs: The ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats Eur. J. Pharm. Biopharm. 2007, 67 (1) 96-105
52. Cuiné, J. F.; McEvoy, C. L.; Charman, W. N.; Pouton, C. W.; Edwards, G. A.; Benameur, H.; Porter, C. J. H. Evaluation of the impact of surfactant digestion on the bioavailability of danazol after oral administration of lipidic self-emulsifying formulations to dogs J. Pharm. Sci. 2008, 97 (2) 995-1012
53. Gao, P.; Morozowich, W. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs Expert Opin. Drug Delivery 2006, 3 (1) 97-110
54. Warren, D. B.; Benameur, H.; Porter, C. J. H.; Pouton, C. W. Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: A mechanistic basis for utility J. Drug Targeting 2010, 18 (10) 704-731
55. Vandecruys, R.; Peeters, J.; Verreck, G.; Brewster, M. E. 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. 2007, 342 (1-2) 168-175
56. Bevernage, J.; Forier, T.; Brouwers, J.; Annaert, P.; Tack, J.; Augustijns, P. Excipient-mediated supersaturation stabilization in Human Intestinal Fluids Mol. Pharmaceutics 2011, 8 (2) 564-570
57. Miller, D. A.; DiNunzio, J. C.; Yang, W.; McGinity, J. W.; Williams, R. O. Enhanced In Vivo Absorption of Itraconazole via Stabilization of Supersaturation Following Acidic-to-Neutral pH Transition Drug Dev. Ind. Pharm. 2008, 34 (8) 890-902
58. Raghavan, S. L.; Schuessel, K.; Davis, A.; Hadgraft, J. Formation and stabilisation of triclosan colloidal suspensions using supersaturated systems Int. J. Pharm. 2003, 261 (1-2) 153-158
59. Raghavan, S. L.; Trividic, A.; Davis, A. F.; Hadgraft, J. Crystallization of hydrocortisone acetate: influence of polymers Int. J. Pharm. 2001, 212 (2) 213-221
60. Usui, F.; Maeda, K.; Kusai, A.; Nishimura, K.; Keiji, Y. Inhibitory effects of water-soluble polymers on precipitation of RS-8359 Int. J. Pharm. 1997, 154 (1) 59-66
61. Sassene, P. J.; Knopp, M. M.; Hesselkilde, J. Z.; Koradia, V.; Larsen, A.; Rades, T.; Müllertz, A. Precipitation of a poorly soluble model drug during in vitro lipolysis: Characterization and dissolution of the precipitate J. Pharm. Sci. 2010, 99 (12) 4982-4991
62. Brouwers, J.; Brewster, M. E.; Augustijns, P. Supersaturating drug delivery systems: The answer to solubility-limited oral bioavailability? J. Pharm. Sci. 2009, 98 (8) 2549-2572
63. Kashchiev, D.; van Rosmalen, G. M. Review: Nucleation in solutions revisited Cryst. Res. Technol. 2003, 38 (7-8) 555-574
64. Khoo, S.-M.; Porter, C. J. H.; Charman, W. N. The formulation of Halofantrine as either non-solubilising PEG 6000 or solubilising lipid based solid dispersions: Physical stability and absolute bioavailability assessment Int. J. Pharm. 2000, 205 (1-2) 65-78
65. Davison, C.; Banks, W.; Fritz, A. The absorption, Distribution and Metabolic Fate of Danazol in Rats, Monkeys and human Volunteers Arch. Int. Pharmacodyn. 1976, 221, 294-310