Handbook of Solvents - George Wypych - ChemTech - Ventech!

15.2.3 An innovative GC method 1119
Table 15.2.3.5. Solvent class and concentration limits in pharmaceutical products
(Data from references 1,6 )
Class
Concentration
limit, ppm
Class
Concentration
limit, ppm
Chloroform 2 60 Hexane 2 290
Dioxane 2 380 Dichloromethane 2 600
Ethanol 3 5000 Tetrahydrofuran 3 5000
15.2.3.2.2 Second example: polycrystalline particles of meprobamate and
ibuprofen
Preparation of polycrystalline particles
The polycrystalline particles were produced using various crystallization processes and designed
to obtain directly compressible particles of pure drug, as tablets cannot be formed by
direct compression of the raw materials.
Spherical crystals of meprobamate
These spherical particles were prepared following the usual preparation process for spherical
crystals described by Guillaume. 7 Spherical crystals of meprobamate appear when stirring
a mixture of three liquids in the crystallizer: methanol allowing meprobamate to
dissolve; water, as a non-solvent, causing meprobamate precipitation; chloroform as a
bridging liquid to gather in its dispersed droplets, meprobamate microcrystallites that finally
form “spherical crystals”.
Ibuprofen agglomerates
Ibuprofen agglomerates were prepared by a phase separation process in a mixture of ethanol
and water (50/50 v/v). 8 The saturated solution obtained at 60°C was constantly stirred and
cooled down to room temperature.
Particle drying conditions
Depending on the melting point of the drugs, different drying conditions were applied in a
ventilated oven. Drastic and progressive temperature conditions were studied for each type
of polycrystalline particles (Table 15.2.3.2).
Spherical crystals of meprobamate
Taking into account the melting point of meprobamate (105°C), temperatures higher than
90°C must be avoided. The different drying conditions were: drastic drying at 90°C for 2
hours and progressive drying at 60°C for 30 minutes, then at 75°C for 30 minutes and finally
at 90°C for one hour.
Ibuprofen agglomerates
This is a particular case; a low drying temperature must be applied because of the very low
melting point of ibuprofen (76°C). The two drying conditions studied were: 40°C for two
hours or 60°C for two hours.
Morphological aspect of the particles
Spherical crystals of meprobamate
Meprobamate crystals appear as more or less rounded opaque particles (Table 15.2.3.3).
Their consistence is friable. Particle size distribution is very narrow. SEM photograph of
meprobamate crystals shows nearly spherical particles; their surface seems apparently
smooth (Figure 15.2.3.5). However, at high magnification, the surface appears to be coated
with flat crystals (Figure 15.2.3.6).