Effects of Biorelevant Media Components on Dissolution Behaviour
of 1,2,4-Thiadiazole Derivative Designed for Alzheimerʼs Disease
G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, 1 Akademicheskaya str., 153045 Ivanovo,
Russia, e-mail: email@example.com
Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severniy pr., 142432 Chernogolovka,
In this study, dissolution behaviour of 1,2,4-thiadiazole derivative (1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-
propan-2-ol) displaying an anti-Alzheimer activity was examined in biorelevant media such as Simulated Gastric Fluid
(SGF, pH 1.2), Fasted State Simulated Gastric Fluid (FaSSGF, pH 1.6) and Fasted State Simulated Intestinal Fluid (FaSSIF,
pH 6.5). It was found that solubility and dissolution rate of 1,2,4-thiadiazole derivative under consideration are not
strongly dependent on pH, whereas these parameters are signiﬁcantly affected by the buffer composition. Dissolution
was found to be more effective in buffers composed of the surfactant micelles. It was demonstrated that considerable
increase in solubility and dissolution rate in SGF is achieved through the interaction of 1,2,4-thiadiazole derivative with
the micelles of sodium dodecyl sulfate. On the contrary, CMC of sodium taurochalate was shifted in the presence of
1,2,4-thiadiazole derivative, therefore, dissolution process is not so efﬁcient in FaSSIF. Interactions occurring between
1,2,4-thiadiazole derivative and the components of biorelevant media were investigated in detail by means of UV/VIS
H-NMR and phase solubility methods.
Keywords: biorelevant media, dissolution, solubility, 1,2,4-thiadiazole derivative, Alzheimer’s disease.
Most drugs are formulated into tablets or capsules. It is
well known that only a drug in soluble form will be
available for the absorption process.
and dissolution rate are key properties controlling the
bioavailability of orally administrated drugs. These
parameters depend on different factors such as particle
size, crystalline form, pH and composition of the ﬂuids
in the GI tract. The last mentioned is of interest for us.
Generally, dissolution of poorly soluble lipophilic
drugs is started in the stomach having an acidic envi-
ronment (pH 1.5 – 3.5) and completed in the ﬁrst
absorptive sites in the small intestine where the perme-
ation of drug through a mucosal barrier into the sys-
temic circulation also takes place. As it is well known,
the content of gastrointestinal environment is rather
complicate. There are some bile salts, phospholipids,
and fatty acids which very often have a substantial
impact on drug dissolution.
[2 – 4]
In this connection, the
in vitro dissolution tests should be carried out in condi-
tions close to the living organism. Moreover, media
simulating the human gastrointestinal tract ﬂuids are
commonly used and an approach mimicking laboratory
animalsʼ gastrointestinal tract ﬂuids would impact on
the preclinical stage of development.
To this end,
biorelevant media simulating the gastrointestinal condi-
tions in humans were developed and used.
are several media which have been proposed for simu-
lation of the content of stomach and small intestine.
For stomach, the simplest dissolution medium is the
Simulated Gastric Fluid (SGF) consisting of sodium
dodecyl sulfate, which is used to reduce the surface
More complicate stomach medium is Fasted
State Simulated Gastric Fluid (FaSSGF) containing physi-
ologically relevant amounts of pepsin, bile salts and
To mimic the medium of small intestine, the
Fasted State Intestinal Fluid (FaSSIF) is usually
It has been documented that biorelevant
media can affect the properties of drugs. For example,
it has been shown that the pancreatin containing
media decrease the dissolution rate of solid phospho-
lipid nanoparticles with griseofulvin.
The results of
statistical investigation of poorly soluble acidic, basic
DOI: 10.1002/cbdv.201700459 Chem. Biodiversity 2018, 15, e1700459 © 2018 Wiley-VHCA AG, Zurich, Switzerland
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