Dissolution Media Simulating Fasted
and Fed States
Margareth Marques
United States Pharmacopeia
Rockville,MD
email:
W hen dissolution testing is ud to forecast the in vivo performance of a drug,it is critical that the in vitro
test mimic the conditions in vivo as cloly as possible.A team of rearchers,led by Dr.Jennifer Dressman of the J.W.Goethe University,Germany,has developed biorelevant gastrointestinal media that simulate the fasted and fed states.The media have been ud to examine the solubility and dissolution characteristics of veral class of drugs including poorly soluble weak bas and lipophilic drugs to assist in predicting in vivo absorption behavior (1). Biorelevant in vitro dissolution test
ing is uful for qual-itative forecasting of formulation and food effects on the dissolution and availability of orally administered drugs.It has been obrved that biorelevant media can provide a more accurate simulation of pharmacokinetic profiles than simulated gastric fluid or simulated intestinal fluid. The u of biorelevant media can have a great impact on the pharmacokinetic studies performed to optimize dosing conditions and product formulation.In addition, biorelevant dissolution testing could be ud to asss bioequivalence of post-approval formulation changes in certain kinds of drugs (2–5).
The formulation and preparation instructions for the biorelevant media developed by Dr.Dressman’s group are detailed below.
Fasted State Simulated Intestinal Fluid (FaSSIF) Sodium taurocholate3mM
Lecithin0.75 mM
NaOH (pellets)0.174 g
NaH2PO4.H2O 1.977 g
u盘病毒开根NaCl 3.093 g
Purified water qs.500 mL
Media has a pH of 6.50 and an osmolality of about 270 mOsmol/kg. Preparation of blank FaSSIF
Dissolve 1.74 g of NaOH (pellets),19.77 g of
NaH2PO4.H2O or 17.19 g of anhydrous NaH2PO4,and 30.93
g of NaCl in 5 L of purified water.Adjust the pH to exactly
6.5 using 1 N NaOH or 1 N HCl.
Preparation of FaSSIF
Dissolve 3.3 g of sodium taurocholate in 500 mL blank FaSSIF.Add 11.8 mL of a solution containing 100 mg /mL lecithin in methylene chloride,forming an emulsion.The methylene chloride is eliminated under vacuum at about 40°C.Draw a vacuum for fifteen minutes at 250 mbar,fol-lowed by 15 minutes at 100 mbar.This results in a clear, micellar solution,having no perceptible odor of methyl-ene chloride.After cooling to room temperature,adjust the volume to 2 L with blank FaSSIF.
For dissolution tests a volume of 500 mL is recom-mended.
Fed State Simulated Intestinal Fluid (FeSSIF)
我家的小仓鼠Sodium taurocholate15 mM
Lecithin 3.75 mM
NaOH (pellets) 4.04 g
Glacial Acetic Acid8.65 g
NaCl11.874 g
Purified water qs.1000 mL
Media has a pH of 5.00 and an osmolality of about 670 mOsmol/kg. Preparation of blank FeSSIF
Dissolve 20.2 g of NaOH (pellets),43.25 g of glacial acetic acid,and 59.37 g of NaCl in 5 L of purified water. Adjust the pH to exactly 5.0 using 1 N NaOH or 1 N HCl. Preparation of FeSSIF
Dissolve 16.5 g of sodium taurocholate in 500 mL of blank FeSSIF.Add 59.08 mL of a solution containing 100 mg/mL lecithin in methylene chloride,forming an emul-sion.The methylene chloride is
eliminated under vacuum at about 40°C.Draw a vacuum for fifteen minutes at 250 mbar,followed by 15 minutes at 100 mbar.This results in a clear to slightly hazy,micellar solution having no percepti-ble odor of methylene chloride.After cooling to room temperature,adjust the volume to 2 L with blank FeSSIF. The recommended volume for simulating conditions in the upper small intestine after a meal is one liter. References
1.Kostwicz,E.S.,Brauns,U.,Becker,R.,Dressman,J.B.–
Forecasting the oral absorption behavior of poorly
对角线的性质
soluble weak bas using solubility and dissolution
studies in biorelevant media.Pharm.Res.,19(3):
345–349,2002.
2.Dressman,J.B.,Reppas,C.– In vitro-in vivo correla-
痔疮形成原因tions for lipophilic,poorly water-soluble drugs.B.T.
Gattefos,93:91–100,2000.
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3.Nicolaides,E.,Symillides,M.,Dressman,J.B.,Reppas,C.
– Biorelevant dissolution testing to predict the plas-
ma profile of lipophilic drugs after oral administra-
力量用英语怎么说tion.Pharm.Res.,18(3):380–388,2001.
4.Horter,D.,Dressman,J.B.– Influence of physicochem-
ical properties on dissolution of drugs in the gas-
trointestinal tract.Adv.Drug Del.Rev.,46:75–87,2001.
5.Lobenberg,R.,Kramer,J.,Shah,V.P.,Amidon,G.L.,
Dressman,J.B.– Dissolution testing as a prognostic
日在tool for oral drug absorption:Dissolution behavior of glibenclamide.Pharm.Res.,17:439–444,2000.
16Dissolution Techno l ogies| MAY 2004
