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Solubility Determination and Modeling for Tirofiban in Several Mixed Solvents at 278.15–323.15 K
journal contribution
posted on 2020-07-07, 14:38 authored by Jianqiang Zhang, Haixia Zhang, Renjie XuDuring the determination
of the solubility of tirofiban, pure methanol, ethanol, isopropanol,
and ethylene glycol (EG) play a major role in dissolution; then, water
is added in sequence for dilution to obtain a dispersion system with
different composition structures, and the concentration gradient between
each mixed liquid is 0.1 (mass fraction). The drug tirofiban whose
solubility is to be tested is added to it, using the isothermal method,
with a high temperature of 323.15 K as the starting point and an interval
of 5 K to a low temperature of 278.15 K. The pressure conditions do
not require special requirements at ordinary atmospheric pressure
environment (101.1 kPa). Results show that when the temperature approaches
the high level, more drugs can be dissolved in the same amount of
solvent. Conversely, when the temperature is close to the low level,
the drug is more difficult to dissolve. The temperature constant,
the proportion of organic solvent is large, the dissolving capacity
of the dispersion system will develop in a positive direction. Conversely,
if the proportion of water is large, the dissolving power will decrease.
Tirofiban crystals accepted the determination of various dissolution
data, including those of the undissolved raw materials that have undergone
X-ray power diffraction (XPRD) detection. The results obtained are
encouraging, no change in the crystal structure of the substance is
found. Three models, Jouyban–Acree model, van’t Hoff–Jouyban–Acree
model, and modified Apelblat–Jouyban–Acree model, were
employed to calculate the experimental tirofiban solubility, and the
relative average deviation (RAD) and the root-mean-square deviation
(RMSD) were not higher than 1.18% and 4.0 × 10–6. The research on tirofiban is not only a simple measurement of the
dissolution data
but more importantly, with the support of these data, more thermodynamic
data can be calculated to obtain tirofiban, which is an indispensable
link between the improvement of the production process of tirofiban
and the synthesis of pharmaceutical preparations.