PMID- 20014280
OWN - NLM
STAT- MEDLINE
DCOM- 20100713
LR  - 20170129
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 99
IP  - 6
DP  - 2010 Jun
TI  - Analysis of nifedipine absorption from soft gelatin capsules using PBPK modeling 
      and biorelevant dissolution testing.
PG  - 2899-904
LID - 10.1002/jps.22026 [doi]
AB  - Delayed absorption of nifedipine when administered as a 20 mg immediate release 
      soft gelatin capsule to fasted volunteers has been reported. Physiologically 
      based pharmacokinetic (PBPK) modeling and in vitro dissolution data were used to 
      explore our hypothesis that at high doses of nifedipine it precipitates in the 
      stomach. Plasma concentration-time profiles following different doses of 
      nifedipine were simulated using commercial PBPK software and compared to in vivo 
      data. In vitro dissolution tests were performed with Adalat 10 mg capsules in 
      different volumes of fasted state simulated gastric fluid (FaSSGF). The 
      discrepancy in plasma concentration-time profiles between the different 
      nifedipine doses could be well simulated, assuming protracted dissolution for the 
      20 mg dose. Nifedipine release from one Adalat 10 capsule in 250 or 500 mL FaSSGF 
      was completed within 15 min whereas when release from two capsules, corresponding 
      to 20 mg nifedipine, was studied in 250 mL FaSSGF, a maximum of about 75% drug 
      dissolved was observed after 15 min followed by a decline in the % dissolved to a 
      final value of approximately 40%. Based on the in silico and in vitro results it 
      can be concluded that the observed prolongation in nifedipine absorption 
      following the 20 mg dose was likely caused by nifedipine precipitation in human 
      stomach.
CI  - (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
FAU - Thelen, Kirstin
AU  - Thelen K
AD  - Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Jantratid, Ekarat
AU  - Jantratid E
FAU - Dressman, Jennifer B
AU  - Dressman JB
FAU - Lippert, Jorg
AU  - Lippert J
FAU - Willmann, Stefan
AU  - Willmann S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Capsules)
RN  - 0 (Pharmaceutical Preparations)
RN  - 9000-70-8 (Gelatin)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
CIN - AAPS J. 2016 Jul;18(4):981-8. PMID: 27106837
MH  - Absorption
MH  - Capsules/*chemistry
MH  - Clinical Trials as Topic
MH  - Gelatin
MH  - Humans
MH  - Nifedipine/*administration & dosage
MH  - Pharmaceutical Preparations/administration & dosage
MH  - Physical Phenomena
MH  - Research
MH  - Software
MH  - Stomach
EDAT- 2009/12/17 06:00
MHDA- 2010/07/14 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/07/14 06:00 [medline]
AID - S0022-3549(15)32599-5 [pii]
AID - 10.1002/jps.22026 [doi]
PST - ppublish
SO  - J Pharm Sci. 2010 Jun;99(6):2899-904. doi: 10.1002/jps.22026.