Handbook of Solvents - George Wypych - ChemTech - Ventech!

1122 Christine Barthélémy, Michel Bauer
content obtained for ethanol in ibuprofen agglomerates is very low, in all drying conditions;
in all cases it is considerably lower than the tolerated limits.
15.2.3.2.3 Third example: polycrystalline particles of paracetamol
Preparation of polycrystalline particles
Paracetamol agglomerates were prepared by the spontaneous precipitation of paracetamol
into a mixture containing hexane, tetrahydrofuran and dichloromethane 9 under stirring. All
the crystals obtained were filtered under vacuum.
Particle drying conditions
The melting point of paracetamol being 169°C and the transition temperature being 156°C,
different drying conditions were tested (Table 15.2.3.2):
• Drastic flash drying: 156°C for either 10 or 30 minutes,
• Drastic drying: 100°C for 2 hours,
• Progressive drying: 60°C for 30 minutes, then 80°C for 30 minutes, and finally,
100°C for 1 hour.
After drastic drying at 100°C and progressive drying, a test with complementary drying
at 156°C was carried out for 10 minutes.
All the recovered crystals were packaged in glass flasks before gas phase chromatography
and other analysis.
Morphological aspect of particles
Several types of texture and morphology are
to be observed in polycrystalline particles,
according to solvent proportions. The most
interesting and particular example are
spherical polycrystalline particles which
have a radial texture (spherolites) and appear
as urchin-like particles (Table
15.2.3.3). SEM reveals the very typical surface
crystallization of the agglomerates
(Figure 15.2.3.9). They are made up of
parallelepipedal flat crystals arranged perpendicularly
to a central nucleus and they
are relatively strong.
The implantation of peripherical crystallites
is perpendicular to the surface. As it
Figure 15.2.3.9. SEM photograph of paracetamol agglomerates
(Photograph from reference 3 ).
has been clearly demonstrated by Ettabia 10 a
nucleus is formed first and then, in a second
step, microcrystallites grow on it.
Residual solvent determination
For organic solvents, gas phase chromatog-
raphy was performed on a Shimadzu GC-14B chromatograph fitted with a Flame Ionization
Detector and a CR-6A Shimadzu integrator.
The packed column was Porapack super Q (Alltech, France), mesh range 80/100,
length 1.80 m, internal diameter 2.16 mm. Carrier gas: anhydrous nitrogen. Injector temperature:
200°C. Detector temperature: 220°C. The chromatographic conditions were: For
dichloromethane, tetrahydrofuran and hexane in paracetamol crystals: isotherm at 150°C,
injection: 5 μl, RT: methanol 0.8 min, dichloromethane 3 min, tetrahydrofuran 7.8 min,
hexane 11.8 min.