Physiological parameters for oral delivery and in vitro testing.
Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro-in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance.
Mudie
Deanna M
DM
College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.
Amidon
Gordon L
GL
Amidon
Gregory E
GE
D000284:Administration, Oral; D001682:Biological Availability; D001826:Body Fluids / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D012995:Solubility
D004304:Dosage Forms
Pharm Res. 1995 Mar;12(3):413-20
7617530
J Pharm Pharmacol. 2006 Aug;58(8):1079-89
16872555
Gut. 1986 Aug;27(8):886-92
3732895
Gut. 1988 Aug;29(8):1035-41
3410329
Dig Dis Sci. 1982 Nov;27(11):961-6
7140493
Eur J Pharm Biopharm. 2001 May;51(3):183-90
11343881
Am J Physiol. 1996 Jul;271(1 Pt 1):G172-83
8760121
Pharm Res. 1998 Feb;15(2):233-8
9523309
Gastroenterol Clin Biol. 1981 Apr;5(4):417-25
7227749
Gastroenterology. 1976 Feb;70(2):203-10
2510
Gastroenterology. 2010 Feb;138(2):469-77, 477.e1
19909743
Int J Pharm. 2005 Mar 23;292(1-2):17-28
15725550
Eur J Pharm Sci. 2005 Mar;24(4):297-303
15734296
Proc Biol Sci. 2004 Dec 22;271(1557):2587-94
15615685
J Lipid Res. 2008 Dec;49(12):2690-5
18693215
Pharm Res. 2009 Jun;26(6):1456-66
19267186
Pharm Res. 1986 Jun;3(3):123-31
24271517
Digestion. 1971;4(6):345-52
5115090
Eur J Drug Metab Pharmacokinet. 1998 Apr-Jun;23(2):97-102
9725464
Pharm Res. 1991 Mar;8(3):360-4
2052525
Dtsch Med Wochenschr. 1970 Oct 2;95(40):2011-6
4919325
J Biomech. 2007;40(6):1202-10
16934271
Am J Dig Dis. 1966 Jul;11(7):503-21
5937767
Aliment Pharmacol Ther. 2005 Nov 15;22(10):971-9
16268972
Eur J Pharm Sci. 2009 Jun 28;37(3-4):434-41
19491035
Food Chem Toxicol. 2001 Mar;39(3):209-28
11278053
Scand J Gastroenterol. 2006 Oct;41(10):1155-64
16990200
Eur J Pharm Biopharm. 2005 Aug;60(3):413-7
15893920
Gastroenterology. 1969 Apr;56(4):758-62
5821083
Clin Nutr. 2009 Dec;28(6):636-41
19500889
J Appl Physiol (1985). 1998 Nov;85(5):1941-8
9804602
J Pharm Sci. 1997 Mar;86(3):372-7
9050808
Gastroenterology. 1972 Apr;62(4):533-9
5020865
Gastroenterology. 1982 Apr;82(4):701-6
7060888
Pharm Res. 1998 Jan;15(1):11-22
9487541
Pharm Res. 2005 Aug;22(8):1215-26
16078131
Ann Acad Med Singap. 2008 Apr;37(4):347-53
18461221
Am J Physiol Gastrointest Liver Physiol. 2001 Jun;280(6):G1227-33
11352816
Int J Pharm. 2000 Nov 4;208(1-2):61-70
11064212
Eur J Pharm Sci. 2010 Jan 31;39(1-3):15-22
19837159
Gut. 1971 Oct;12(10):863
5123288
Br Med J. 1972 Apr 8;2(5805):104-6
5018285
Gastroenterology. 1986 Apr;90(4):958-62
3949122
Mol Pharm. 2010 Oct 4;7(5):1527-32
20726533
Gut. 1984 May;25(5):491-9
6714793
Scand J Gastroenterol. 1971;6(4):313-7
5561176
Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G1037-48
12842820
Pharm Res. 2008 Jul;25(7):1663-76
18404251
Eur J Pharm Biopharm. 2008 Sep;70(1):313-25
18434110
AAPS J. 2009 Jun;11(2):277-85
19412669
Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G159-63
11408268
Int J Pharm. 2008 Dec 8;364(2):213-26
18602774
Adv Drug Deliv Rev. 2005 Jun 15;57(8):1210-22
15935870
J Nutr. 2006 Apr;136(4):913-9
16549450
Gastroenterology. 1990 Nov;99(5):1275-82
2210236
J Am Acad Dermatol. 1985 Feb;12(2 Pt 1):308-12
3838321
Am J Physiol Gastrointest Liver Physiol. 2000 Apr;278(4):G604-16
10762615
Drug Dev Ind Pharm. 2003 Feb;29(2):231-9
12648020
Pharm Res. 2005 Apr;22(4):628-35
15846471
Scand J Gastroenterol. 1974;9(6):567-70
4419676
Aliment Pharmacol Ther. 2003 Nov 15;18(10):1039-48
14616171
Pharm Res. 1990 Jul;7(7):756-61
2395805
Pharm Res. 1996 Jan;13(1):163-7
8668668
Drug Dev Ind Pharm. 2007 Jun;33(6):595-605
17613024
Am J Physiol. 1997 Aug;273(2 Pt 1):G553-8
9277437
Proc Natl Acad Sci U S A. 2010 May 4;107(18):8201-6
20404209
J Clin Gastroenterol. 2009 Jul;43(6):527-33
19318982
Clin Chim Acta. 1986 Sep 15;159(2):123-32
3769204
Pharm Res. 2005 Dec;22(12):2141-51
16247711
J Pharm Sci. 2006 Jan;95(1):116-25
16315223
J Nutr. 2000 Jan;130(1):122-7
10613778
J Pharm Sci. 2006 Feb;95(2):372-83
16374852
J Pharm Pharmacol. 2004 Apr;56(4):453-62
15099440
J Pharm Sci. 2009 Mar;98(3):1177-92
18680176
Int J Pharm. 2005 Feb 16;290(1-2):121-7
15664137
Pharm Res. 1997 Apr;14(4):497-502
9144738
Scand J Gastroenterol Suppl. 1975;32:11-144
235788
Crit Rev Food Sci Nutr. 2006;46(8):649-63
17092830
J Pharm Sci. 2008 Nov;97(11):4815-29
18314890
Pharm Res. 1998 May;15(5):698-705
9619777
AAPS J. 2006 Jan 03;7(4):E857-64
16594638
Gut. 1973 Jul;14(7):513-8
4729918
Int J Pharm. 2004 Jul 26;279(1-2):9-17
15234789
Digestion. 1968;1(2):65-77
4877619
Dig Dis Sci. 1987 May;32(5):472-80
3646103
Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G894-901
19779010
Eur J Pharm Sci. 2006 Nov;29(3-4):306-14
16982177
Gut. 1984 Apr;25(4):405-11
6706220
J Clin Invest. 1957 Oct;36(10):1521-36
13475490
Dig Liver Dis. 2004 Aug;36(8):505-12
15334769
J Clin Invest. 1971 Apr;50(4):890-900
4926261
Mol Pharm. 2009 Jan-Feb;6(1):29-39
19183104
Pharm Res. 2006 Jan;23(1):165-76
16308672
Pharm Res. 2000 Jul;17(7):891-4
10990211
J Pharm Pharmacol. 2007 Nov;59(11):1527-36
17976264
Gastroenterology. 1969 Sep;57(3):241-52
5808483