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| − | + | The dispersion and precipitation behavior [http://www.selleckchem.com/products/epacadostat-incb024360.html Epacadostat mouse] of a poorly soluble NCE in various lipid-based formulations using 96-well microtiter plate in various biological fluids such as SIF, FaSSIF and FeSSIF was reported 27. The authors have short-listed three formulations based on precipitation kinetics (fast, slow and no precipitation) and studied the pharmacokinetics in dogs. There was a good correlation between the precipitation kinetics observed in biological fluids versus AUC values, where the rank ordering was fast[http://en.wikipedia.org/wiki/ATPase ATPase] was developed and compared with two reference SMEDDS formulations. All three formulations were evaluated for in vitro dissolution (in pH 1.2, 4.5 and 6.8) and in vivo in dogs. Strong Level A correlations were achieved for fraction dissolved versus fraction absorbed. The author concluded that BCS class-II compounds will behave as class-I compounds when administered in optimized SMEDDS formulation. Similar Level A IVIVC correlations were established for various poorly water-soluble drugs such as ritonavir and lopinavir administered as lipid formulations in soft gelatin capsules 90?and?91. Various IVIVC examples from the literature using in vitro dispersion/dissolution/precipitation and in vivo data are presented in Table 3. Even though achieving correlation with this test appears simple, there are many limitations involved. Firstly, if the precipitated drug redissolves at later points in the intestine due to pH change [http://www.selleckchem.com/products/MG132.html selleck chemicals llc] or solid state change of the precipitated drug, the obtained IVIVC correlation or rank ordering will not be valid. Secondly and most importantly it is not only the dispersion but also the lipid digestion by gastric and pancreatic lipases that plays an important role in maintaining the drug in the solubilized state. Hence, even if the drug remains in a solubilized state after dispersion, it can very well precipitate due to lipid digestion. The role of lipid digestion in achieving IVIVC for lipid formulations is described in the following section. Out of all the methods used for establishing IVIVC for lipid-based formulations, in vitro lipolysis plays a major role due to its capability to simulate the most important steps in the absorption of lipid-based formulations such as dispersion and digestion. The limitation of the in vitro dispersion/precipitation test to predict the in vivo performance can be overcome by incorporating in vitro lipolysis. | |
Версія за 07:29, 22 червня 2017
The dispersion and precipitation behavior Epacadostat mouse of a poorly soluble NCE in various lipid-based formulations using 96-well microtiter plate in various biological fluids such as SIF, FaSSIF and FeSSIF was reported 27. The authors have short-listed three formulations based on precipitation kinetics (fast, slow and no precipitation) and studied the pharmacokinetics in dogs. There was a good correlation between the precipitation kinetics observed in biological fluids versus AUC values, where the rank ordering was fastATPase was developed and compared with two reference SMEDDS formulations. All three formulations were evaluated for in vitro dissolution (in pH 1.2, 4.5 and 6.8) and in vivo in dogs. Strong Level A correlations were achieved for fraction dissolved versus fraction absorbed. The author concluded that BCS class-II compounds will behave as class-I compounds when administered in optimized SMEDDS formulation. Similar Level A IVIVC correlations were established for various poorly water-soluble drugs such as ritonavir and lopinavir administered as lipid formulations in soft gelatin capsules 90?and?91. Various IVIVC examples from the literature using in vitro dispersion/dissolution/precipitation and in vivo data are presented in Table 3. Even though achieving correlation with this test appears simple, there are many limitations involved. Firstly, if the precipitated drug redissolves at later points in the intestine due to pH change selleck chemicals llc or solid state change of the precipitated drug, the obtained IVIVC correlation or rank ordering will not be valid. Secondly and most importantly it is not only the dispersion but also the lipid digestion by gastric and pancreatic lipases that plays an important role in maintaining the drug in the solubilized state. Hence, even if the drug remains in a solubilized state after dispersion, it can very well precipitate due to lipid digestion. The role of lipid digestion in achieving IVIVC for lipid formulations is described in the following section. Out of all the methods used for establishing IVIVC for lipid-based formulations, in vitro lipolysis plays a major role due to its capability to simulate the most important steps in the absorption of lipid-based formulations such as dispersion and digestion. The limitation of the in vitro dispersion/precipitation test to predict the in vivo performance can be overcome by incorporating in vitro lipolysis.
