Drug delivery applications for superporous hydrogels

Expert Opinion on Drug Delivery

Volumn 9, Issue 1, 2012, Pages 71-89

  Mastropietro, David J ^c   Omidian, Hossein ^a   Park, Kinam ^b,c  

^a NOVA SOUTHEASTERN UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

^c PURDUE UNIVERSITY   (United States)

Author keywords

Diet aid; Drug delivery; Gastric retention drug delivery; Gastroretentive dosage form; Hybrid hydrogels; Intestinal drug delivery; Peroral protein delivery; Superdisintegrant; Superporous hybrid hydrogels; Superporous hydrogels

Indexed keywords

CARBOMER; CELLULOSE; CHITOSAN DERIVATIVE; HYDROXYPROPYLMETHYLCELLULOSE; IBUPROFEN; O CARBOXYMETHYL CHITOSAN; PANTOPRAZOLE; POLY(ACRYLIC ACID CO ACRYLAMIDE); POLY(METHACRYLIC ACID CO ACRYLAMIDE); POLY(N ISOPROPYLACRYLAMIDE); POLYACRYLIC ACID; POLYMER; POVIDONE; PROTON PUMP INHIBITOR; SUPERABSORBENT POLYMER; UNCLASSIFIED DRUG;

BIOAVAILABILITY; BIOCOMPATIBILITY; DRUG DELIVERY SYSTEM; DRUG MANUFACTURE; DRUG RELEASE; DRUG TRANSPORT; GASTROINTESTINAL TRACT; HUMAN; HYDROGEL; NONHUMAN; PARTICLE SIZE; REVIEW; SUPERPOROUS HYDROGEL;

ANIMALS; DELAYED-ACTION PREPARATIONS; DRUG CARRIERS; HUMANS; HYDROGELS; HYDROGEN-ION CONCENTRATION; INTESTINES; MATERIALS TESTING; MICROSCOPY, ELECTRON, SCANNING; PEPTIDES; POROSITY; PROTEINS; STOMACH; STRESS, MECHANICAL; SURFACE PROPERTIES;

EID: 84255167323     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2012.641950     Document Type: Review

References (108)

1. Chen J, Park H, Park K. Synthesis of superporous hydrogels: hydrogels with fast swelling and superabsorbent properties. J Biomed Mater Res 1999;44(1):53-62
2. Chaterji S, Kwon IK, Park K. Smart polymeric gels: Redefining the limits of biomedical devices. Prog Polym Sci 2007;32(8-9):1083-122 (Pubitemid 47198296)
3. Gemeinhart RA, Park H, Park K. Pore structure of superporous hydrogels. Polym Adv Technol 2000;11(8-12):617-25 (Pubitemid 32021077)
4. Omidian H, Park K. Swelling agents and devices in oral drug delivery. J Drug Deliv Sci Technol 2008;18(2):83-93 (Pubitemid 351449969)
5. Prinderre P, Sauzet C, Fuxen C. Advances in gastro retentive drug-delivery systems. Expert Opin Drug Deliv 2011;8(9):1189-203
6. Chawla G, Gupta P, Koradia V, et al. A means to address regional variability in intestinal drug absorption. Pharm Technol 2003;27(6):50-68 (Pubitemid 37101890)
7. Gemeinhart RA, Chen J, Park H, et al. pH-sensitivity of fast responsive superporous hydrogels. J Biomater Sci Polym Ed 2000;11(12):1371-80 (Pubitemid 32208316)
8. Gupta NV, Shivakumar HG. Preparation and characterization of superporous hydrogels as pH-sensitive drug delivery system for pantoprazole sodium. Curr Drug Del 2009;6(5):505-10
9. Milosavljevic NB, Milasinovic NZ, Popovic IG, et al. Preparation and characterization of pH-sensitive hydrogels based on chitosan, itaconic acid and methacrylic acid. Polym Int 2011;60(3):443-52
10. Hoffman AS. Hydrogels for biomedical applications. Adv Drug Del Rev 2002;54(1):3-12 (Pubitemid 34081178)
11. Kim D, Park K. Swelling and mechanical properties of superporous hydrogels of poly (acrylamide-co-acrylic acid)/polyethylenimine interpenetrating polymer networks. Polymer (Guildf) 2004;45(1):189-96 (Pubitemid 38031451)
12. Wu XS, Hoffman AS, Yager P. Synthesis and characterization of thermally reversible macroporous poly(NIsopropylacrylamide) hydrogels. J Polym Sci Pol Chem 1992;30(10):2121-9 (Pubitemid 23614896)
13. Tokuyama H, Kanehara A. Novel synthesis of macroporous poly(Nisopropylacrylamide) hydrogels using oil-in-water emulsions. Langmuir 2007;23(22):11246-51 (Pubitemid 350069354)
14. Badiger MV, McNeill ME, Graham NB. Porogens in the preparation of microporous hydrogels based on poly(ethylene oxides). Biomaterials 1993;14(14):1059-63 (Pubitemid 23342098)
15. Lee WF, Lin YH. Effect of porosigen on the swelling behavior and drug release of porous N-isopropylacrylamide/poly(ethylene glycol) monomethylether acrylate copolymeric hydrogels. J Appl Polym Sci 2006;102(6):5490-9
16. Patel VR, Amiji MM. Preparation and characterization of freeze-dried chitosan-poly(ethylene oxide) hydrogels for site-specific antibiotic delivery in the stomach. Pharm Res 1996;13(4):588-93 (Pubitemid 26119684)
17. Risbud MV, Hardikar AA, Bhat SV, et al. pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. J Control Release 2000;68(1):23-30 (Pubitemid 30407059)
18. Omidian H, Qiu Y, Kim D, et al. Hydrogels having enhanced elasticity and mechanical strength properties. US6960617; 2005
19. Omidian H, Rocca JG. Formation of strong superporous hydrogels. US7056957; 2006
20. Omidian H, Rocca JG, Park K. Advances in superporous hydrogels. J Control Release 2005;102(1):3-12 (Pubitemid 40093771)
21. Dorkoosh FA, Verhoef JC, Borchard G, et al. Development and characterization of a novel peroral peptide drug delivery system. J Control Release 2001;71(3):307-18 (Pubitemid 32276050)
22. Polnok A, Verhoef JC, Borchard G, et al. In vitro evaluation of intestinal absorption of desmopressin using drug-delivery systems based on superporous hydrogels. Int J Pharm 2004;269(2):303-10 (Pubitemid 38045294)
23. Dorkoosh FA, Verhoef JC, Verheijden JHM, et al. Peroral absorption of octreotide in pigs formulated in delivery systems on the basis of superporous hydrogel polymers. Pharm Res 2002;19(10):1532-6 (Pubitemid 35266559)
24. Yin LC, Fei LK, Cui FY, et al. Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/Ocarboxymethyl chitosan interpenetrating polymer networks. Biomaterials 2007;28(6):1258-66
25. Milasinovic N, Kalagasidis Krusic M, Knezevic-Jugovic Z, et al. Hydrogels of N-isopropylacrylamide copolymers with controlled release of a model protein. Int J Pharm 2010;383(1-2):53-61
26. Rocca JG, Omidian H, Shah K. Commercial status of gastric retention technologies. Drug Deliv Technol 2005;5(4):40-6
27. Rocca JG, Shah K, Omidian H. Superporous hydrogels containing solid and semi-solid carriers. Gattefosse Tech Bull 2004;97:73-84
28. Dorkoosh FA, Borchard G, Rafiee-Tehrani M, et al. Evaluation of superporous hydrogel (SPH) and SPH composite in porcine intestine ex-vivo: assessment of drug transport, morphology effect, and mechanical fixation to intestinal wall. Eur J Pharm Biopharm 2002;53(2):161-6 (Pubitemid 34189789)
29. Bardonnet PL, Faivre V, Pugh WJ, et al. Gastroretentive dosage forms: overview and special case of Helicobacter pylori. J Control Release 2006;111(1-2):1-18 (Pubitemid 43289989)
30. Dhumal RS, Rajmane ST, Dhumal ST, et al. Design and evaluation of bilayer floating tablets of cefuroxime axetil for bimodal release. J Sci Ind Res 2006;65(10):812-16 (Pubitemid 44593180)
31. Rokhade AP, Patil SA, Belhekar AA, et al. Preparation and evaluation of cellulose acetate butyrate and poly(ethylene oxide) blend microspheres for gastroretentive floating delivery of repaglinide. J Appl Polym Sci 2007;105(5):2764-71 (Pubitemid 47168963)
32. Groning R, Berntgen M, Georgarakis M. Acyclovir serum concentrations following peroral administration of magnetic depot tablets and the influence of extracorporal magnets to control gastrointestinal transit. Eur J Pharm Biopharm 1998;46(3):285-91 (Pubitemid 29057675)
33. Atyabi F, Sharma HL, Mohammad HAH, et al. Controlled drug release from coated floating ion exchange resin beads. J Control Release 1996;42(1):25-8 (Pubitemid 26297872)
34. Umamaheswari RB, Jain S, Tripathi PK, et al. Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance of Helicobacter pylori. Drug Deliv 2002;9(4):223-31 (Pubitemid 35397024)
35. Han W, Omidian H, Rocca JG. A novel acrylate ester-based superporous hydrogel. The 32nd Annual Meeting of the Controlled Release Society 2005; Miami, Florida, USA; 2005
36. Park H, Park K, Kim D. Preparation and swelling behavior of chitosan-based superporous hydrogels for gastric retention application. J Biomed Mater Res A 2006;76A(1):144-50 (Pubitemid 43075692)
37. Park J, Kim D. Release behavior of amoxicillin from glycol chitosan superporous hydrogels. J Biomater Sci Polym Ed 2009;20(5-6):853-62
38. Gupta NV, Shivakumar HG. Development of a gastroretentive drug delivery system based on superporous hydrogel. Trop J Pharm Res 2010;9(3):257-64
39. Gupta NV, Shivakumar HG. Preparation and characterization of superporous hydrogels as gastroretentive drug delivery system for rosiglitazone maleate. Daru J Pharm Sci 2010;18(3):200-10
40. Dorkoosh FA, Broekhuizen CAN, Borchard G, et al. Transport of octreotide and evaluation of mechanism of opening the paracellular tight junctions using superporous hydrogel polymers in Caco-2 cell monolayers. J Pharm Sci 2004;93(3):743-52 (Pubitemid 38332306)
41. Dorkoosh FA, Brussee J, Verhoef JC, et al. Preparation and NMR characterization of superporous hydrogels (SPH) and SPH composites. Polymer (Guildf) 2000;41(23):8213-20 (Pubitemid 30490110)
42. Dorkoosh FA, Setyaningsih D, Borchard G, et al. Effects of superporous hydrogels on paracellular drug permeability and cytotoxicity studies in Caco-2 cell monolayers. Int J Pharm 2002;241(1):35-45 (Pubitemid 34667064)
43. Dorkoosh FA, Verhoef JC, Ambagts MHC, et al. Peroral delivery systems based on superporous hydrogel polymers: release characteristics for the peptide drugs buserelin, octreotide and insulin. Eur J Pharm Sci 2002;15(5):433-9 (Pubitemid 34567105)
44. Dorkoosh FA, Verhoef JC, Borchard G, et al. Intestinal absorption of human insulin in pigs using delivery systems based on superporous hydrogel polymers. Int J Pharm 2002;247(1-2):47-55 (Pubitemid 35341138)
45. Yin LC, Zhao ZM, Hu YZ, et al. Polymer-protein interaction, water retention, and biocompatibility of a stimuli-sensitive superporous hydrogel containing interpenetrating polymer networks. J Appl Polym Sci 2008;108(2):1238-48
46. Yin LC, Ding JY, Fei LK, et al. Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles. Int J Pharm 2008;350(1-2):220-9
47. Yin LC, Zhao X, Cui LM, et al. Cytotoxicity and genotoxicity of superporous hydrogel containing interpenetrating polymer networks. Food Chem Toxicol 2009;47(6):1139-45
48. Yin LC, Ding JY, Zhang J, et al. Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin. Biomaterials 2010;31(12):3347-56
49. Tang C, Yin CH, Pei YY, et al. New superporous hydrogels composites based on aqueous Carbopol solution (SPHCcs): synthesis, characterization and in vitro bioadhesive force studies. Eur Polym J 2005;41(3):557-62
50. Savina IN, Mattiasson B, Galaev IY. Graft polymerization of acrylic acid onto macroporous polyacrylamide gel (cryogel) initiated by potassium diperiodatocuprate. Polymer (Guildf) 2005;46(23):9596-603 (Pubitemid 41460466)
51. Cheng SX, Zhang JT, Zhuo RX. Macroporous poly(Nisopropylacrylamide) hydrogels with fast response rates and improved protein release properties. J Biomed Mater Res A 2003;67A(1):96-103
52. Pourjavadi A, Barzegar S. Synthesis and evaluation of pH and thermosensitive pectin-based superabsorbent hydrogel for oral drug delivery systems. Starch Starke 2009;61(3-4):161-72
53. Horn JR, Howden CW. Similarities and differences among delayed-release proton-pump inhibitor formulations. Aliment Pharmacol Ther 2005;22:20-4 (Pubitemid 41783983)
54. Omidina H, Park K. Engineered High Swelling Hydrogels. In: Ottenbrite RM, Park K, Okano T, editors. Biomedical applications of hydrogels handbook. Springer; New York: 2010. p. 365
55. Yang SC, Fu YR, Hoon S, et al. Application of poly(acrylic acid) superporous hydrogel microparticles as a super-disintegrant in fast-disintegrating tablets. J Pharm Pharmacol 2004;56(4):429-36
56. Askari F, Nafisi S, Omidian H, et al. Synthesis and characterization of acrylic-based superabsorbents. J Appl Polym Sci 1993;50(10):1851-5
57. Yang SC, Fu YR, Jeong SH, et al. Preparation and characterization of poly (acrylic acid) superporous hydrogels as a super-disintegrant in fast disintegrating tablets. Abstr Pap Am Chem Soc 2003;226:228-PMSE
58. Pradny M, Slouf M, Martinova L, et al. Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 7: methods of preparation and comparison of resulting physical properties. E Polymers 2010;043:1-12
59. Cetin D, Kahraman AS, Gumusderelioglu M. Novel scaffolds based on poly(2-hydroxyethyl methacrylate) superporous hydrogels for bone tissue engineering. J Biomater Sci Polym Ed 2011;22(9):1157-78
60. Keskar V, Gandhi M, Gemeinhart EJ, et al. Initial evaluation of vascular ingrowth into superporous hydrogels. J Tissue Eng Regen M 2009;3(6):486-90
61. Jayakrishnan A, Mohanty M, Mandalam R, et al. Endovascular embolization using hydrogel microspheres. J Mater Sci Mater Med 1994;5(9):723-7 (Pubitemid 24357969)
62. Park H. Superporous hydrogels for pharmaceutical & other applications. Drug Deliv Technol 2002;2:38-44
63. Benson JR. Highly porous polymers. Am Lab 2003;35(10):49-52
64. Dorkoosh FA, Stokkel MPM, Blok D, et al. Feasibility study on the retention of superporous hydrogel composite polymer in the intestinal tract of man using scintigraphy. J Control Release 2004;99(2):199-206 (Pubitemid 39222106)
65. Chen J, Blevins WE, Park H, et al. Gastric retention properties of superporous hydrogel composites. J Control Release 2000;64(1-3):39-51 (Pubitemid 30035306)
66. Rzaev ZMO, Dincer S, Piskin E. Functional copolymers of N-isopropylacrylamide for bioengineering applications. Prog Polym Sci 2007;32(5):534-95 (Pubitemid 46670215)
67. Kim D, Seo K, Park K. Polymer composition and acidification effects on the swelling and mechanical properties of poly(acrylamide-co-acrylic acid) superporous hydrogels. J Biomater Sci Polym Ed 2004;15(2):189-99 (Pubitemid 38380169)
68. Haxhinasto KB, English AE, Moy AB. Equilibrium and non-equilibrium charge-dependent quantification of endothelial cell hydrogel scaffolds. J Mater Sci Mater Med 2008;19(5):1999-2008 (Pubitemid 351422698)
69. Mun G, Suleimenov I, Park K, et al. Superabsorbent Hydrogels. In: Ottenbrite RM, Park K, Okano T, editors. Biomedical applications of hydrogels handbook. Springer; New York: 2010. p. 375-91
70. Tang C, Yin LC, Yu J, et al. Swelling behavior and biocompatibility of carbopol-containing superporous hydrogel composites. J Appl Polym Sci 2007;104(5):2785-91 (Pubitemid 46707265)
71. Kabiri K, Omidian H, Hashemi SA, et al. Synthesis of fast-swelling superabsorbent hydrogels: Effect of crosslinker type and concentration on porosity and absorption rate. Eur Polym J 2003;39(7):1341-8
72. Han W, Omidian H, Rocca JG. Dynamic swelling of superporous hydrogels under compression. American Association of Pharmaceutical Scientists 2005; Tennessee, USA: 2005
73. Omidian H, Park K, Rocca JG. Recent developments in superporous hydrogels. J Pharm Pharmacol 2007;59(3):317-27 (Pubitemid 47050896)
74. Gavrilas C, Omidian H, Rocca JG. A novel gastric simulator. The 32nd Annual Meeting of the Controlled Release Society 2005; Miami, Florida, USA; 2005
75. Gavrilas C, Omidian H, Rocca JG. A novel simulator to evaluate fatigue properties of superporous hydrogels. 8th US-Japan Symposium on Drug Delivery Systems 2005; Hawaii, USA; 2005
76. Gemeinhart RA, Park H, Park K. Effect of compression on fast swelling of poly (acrylamide-co-acrylic acid) superporous hydrogels. J Biomed Mater Res 2001;55(1):54-62 (Pubitemid 32162145)
77. Chen J, Park K. Superporous hydrogels: fast responsive hydrogel systems. J Macromol Sci Pure Appl Chem 1999;A36(7-8):917-30 (Pubitemid 129613814)
78. Chen J, Park K. Synthesis and characterization of superporous hydrogel composites. J Control Release 2000;65(1-2):73-82 (Pubitemid 30122917)
79. Park K, Chen J, Park H. Superporous Hydrogel Composites: A New Generation of Hydrogels with Fast Swelling Kinetics, High Swelling Ratio and High Mechanical Strength. In: Ottenbrite R, Kim SW, editors. Polymeric Drugs and Drug Delivery systems. CRC Press; Boca Raton: 2001. p. 145-56
80. Omidian H, Rocca JG, Park K. Elastic, superporous hydrogel hybrids of polyacrylamide and sodium alginate. Macromol Biosci 2006;6(9):703-10 (Pubitemid 44544929)
81. Hou XP, Siow KS. Novel interpenetrating polymer network electrolytes. Polymer (Guildf) 2001;42(9):4181-8 (Pubitemid 32167571)
82. Mahmoud EA, Bendas ER, Mohamed MI. Effect of formulation parameters on the preparation of superporous hydrogel self-nanoemulsifying drug delivery system (SNEDDS) of carvedilol. AAPS PharmSciTech 2010;11(1):221-5
83. Baek N, Park K, Park JH, et al. Control of the swelling rate of superporous hydrogels. J Bioact Compatible Polym 2001;16(1):47-57 (Pubitemid 32588523)
84. Huh KM, Baek N, Park K. Enhanced swelling rate of poly(ethylene glycol)- grafted superporous hydrogels. J Bioact Compatible Polym 2005;20(3):231-43 (Pubitemid 40663646)
85. Seo KW, Kim DJ, Park KN. Swelling properties of poly(AM-co-AA)/chitosan pH sensitive superporous hydrogels. J Ind Eng Chem 2004;10(5):794-800
86. Yin LC, Fei LK, Tang C, et al. Synthesis, characterization, mechanical properties and biocompatibility of interpenetrating polymer network-super-porous hydrogel containing sodium alginate. Polym Int 2007;56:1563-71 (Pubitemid 350142452)
87. Omidian H, Park K. Experimental design for the synthesis of polyacrylamide superporous hydrogels. J Bioact Compatible Polym 2002;17(6):433-50 (Pubitemid 36622332)
88. Mahdavinia GR, Mousavi SB, Karimi F, et al. Synthesis of porous poly (acrylamide) hydrogels using calcium carbonate and its application for slow release of potassium nitrate. Expr Polym Lett 2009;3(5):279-85
89. Kabiri K, Omidian H, Hashemi SA, et al. Concise synthesis of fast-swelling superabsorbent hydrogels: Effect of initiator concentration on porosity and absorption rate. J Polym Mater 2003;20(1):17-22
90. Kabiri K, Omidian H, Zohuriaan-Mehr MJ. Novel approach to highly porous superabsorbent hydrogels: synergistic effect of porogens on porosity and swelling rate. Polym Int 2003;52(7):1158-64 (Pubitemid 36887412)
91. Kabiri K, Zohuriaan-Mehr MJ. Superabsorbent hydrogel composites. Polym Adv Technol 2003;14(6):438-44 (Pubitemid 36755836)
92. Hradil J, Horak D. Characterization of pore structure of PHEMA-based slabs. React Funct Polym 2005;62(1):1-9
93. Omidian H, Park K, Rocca JG. Experimental design in the preparation of modified HEMA-based superporous hydrogels in an aqueous medium. Int J Polym Mater 2010;59(9):693-709
94. Omidian H, Rocca JG. Superporous hydrogels for heavy-duty applications. US7988992; 2011
95. Omidian H, Park K, Kandalam U, et al. Swelling and mechanical properties of modified HEMA-based superporous hydrogels. J Bioact Compatible Polym 2010;25(5):483-97
96. Yang SC, Park KN, Rocca JG. Semi-interpenetrating polymer network superporous hydrogels based on poly(3-sulfopropyl acrylate, potassium salt) and poly(vinyl alcohol): synthesis and characterization. J Bioact Compatible Polym 2004;19(2):81-100 (Pubitemid 38560188)
97. Qiu Y, Park K. Superporous IPN hydrogels having enhanced mechanical properties. AAPS PharmSciTech 2003;4(4):E51
98. Park H, Kim D. Swelling and mechanical properties of glycol chitosan/poly(vinyl alcohol) IPN-type superporous hydrogels. J Biomed Mater Res A 2006;78A(4):662-7 (Pubitemid 44300019)
99. Park J, Kim D. Effect of polymer solution concentration on the swelling and mechanical properties of glycol chitosan superporous hydrogels. J Appl Polym Sci 2010;115(6):3434-41
100. Kaneko T, Asoh TA, Akashi M. Ultrarapid molecular release from poly(N-isopropylacrylamide) hydrogels perforated using silica nanoparticle networks. Macromol Chem Phys 2005;206(5):566-74 (Pubitemid 40811979)
101. Abd El-Rehim HA, Hegazy ESA, Diaa DA. Characterization of super-absorbent material based on carboxymethylcellulose sodium salt prepared by electron beam irradiation. J Macromol Sci Pure Appl Chem 2006;A43(1):101-13 (Pubitemid 43102694)
102. Chen J, Park K. Synthesis of fast-swelling, superporous sucrose hydrogels. Carbohydr Polym 2000;41(3):259-68 (Pubitemid 30544750)
103. Kuang J, Yuk KY, Huh KM. Polysaccharide-based superporous hydrogels with fast swelling and superabsorbent properties. Carbohydr Polym 2011;83(1):284-90
104. Gils PS, Ray D, Sahoo PK. Characteristics of xanthan gum-based biodegradable superporous hydrogel. Int J Biol Macromol 2009;45(4):364-71
105. Omidian H, Gavrilas C, Han W, et al. Very-pure superabsorbent hydrogels having outstanding swelling properties. US20080206339; 2008
106. Park SE, Nho YC, Lim YM, et al. Preparation of pH-sensitive poly(vinyl alcohol-g-methacrylic acid) and poly(vinyl alcohol-g-acrylic acid) hydrogels by gamma ray irradiation and their insulin release behavior. J Appl Polym Sci 2004;91(1):636-43
107. Francis S, Mitra D, Dhanawade BR, et al. Gamma radiation synthesis of rapid swelling superporous polyacrylamide hydrogels. Radiat Phys Chem 2009;78(11):951-3
108. Li G, Omidian H, Rocca JG. Solvent effects on the swelling properties of superporous hydrogels. American Association of Pharmaceutical Scientists 2005; Tennessee, USA: 2005