TY - JOUR

T1 - Batch cooling crystallization and pressure filtration of sulphathiazole

T2 - the influence of solvent composition

AU - Häkkinen, Antti

AU - Pöllänen, Kati

AU - Karjalainen, Milja

AU - Rantanen, Jukka

AU - Louhi-Kultanen, Marjatta

AU - Nyström, Lars

PY - 2005/2

Y1 - 2005/2

N2 - Currently there is a great interest in new process analytical approaches to increase the process understanding of pharmaceutical unit operations. In the present study, the influence of the solvent composition on the material properties and, further, on the filtration characteristics, of different crystal suspensions obtained through an unseeded batch-cooling-crystallization process was studied. Sulphathiazole, which is an antibiotic agent with multiple polymorphic forms, was produced by performing laboratory-scale cooling crystallization experiments from five different mixtures of water and propan-1-ol (n-propanol). The size, shape and polymorphic composition of the crystals produced were characterized with a scanning electron microscope, with a novel automated image analyser and with an X-ray powder diffractometer. All of the monitored crystal properties were found to clearly differ between the samples obtained from different solvents. The crystals produced in the batch-cooling-crystallization experiments were separated from the crystallizing solvents using a batch-type pressure Nutsche filter, and the filtration characteristics of the suspensions were evaluated on the basis of average filter-cake porosities and average specific cake resistances, which were determined from the experimentally obtained filtration data. Comparison between the calculated filtration characteristics revealed that considerable differences existed between the different suspensions, and it could therefore be concluded that the pressure-filtration process was influenced by the composition of the crystallizing solvent. The filterability of all the studied sulphathiazole suspensions was considered to be rather good on the basis of the relatively low cake porosities (0.51-0.63), which were accompanied with low average specific cake resistances [(8.7 x 10(7))-(1.2 x 10(9)) m/kg].

AB - Currently there is a great interest in new process analytical approaches to increase the process understanding of pharmaceutical unit operations. In the present study, the influence of the solvent composition on the material properties and, further, on the filtration characteristics, of different crystal suspensions obtained through an unseeded batch-cooling-crystallization process was studied. Sulphathiazole, which is an antibiotic agent with multiple polymorphic forms, was produced by performing laboratory-scale cooling crystallization experiments from five different mixtures of water and propan-1-ol (n-propanol). The size, shape and polymorphic composition of the crystals produced were characterized with a scanning electron microscope, with a novel automated image analyser and with an X-ray powder diffractometer. All of the monitored crystal properties were found to clearly differ between the samples obtained from different solvents. The crystals produced in the batch-cooling-crystallization experiments were separated from the crystallizing solvents using a batch-type pressure Nutsche filter, and the filtration characteristics of the suspensions were evaluated on the basis of average filter-cake porosities and average specific cake resistances, which were determined from the experimentally obtained filtration data. Comparison between the calculated filtration characteristics revealed that considerable differences existed between the different suspensions, and it could therefore be concluded that the pressure-filtration process was influenced by the composition of the crystallizing solvent. The filterability of all the studied sulphathiazole suspensions was considered to be rather good on the basis of the relatively low cake porosities (0.51-0.63), which were accompanied with low average specific cake resistances [(8.7 x 10(7))-(1.2 x 10(9)) m/kg].

KW - 1-Propanol

KW - Chemical Precipitation

KW - Cold Temperature

KW - Combinatorial Chemistry Techniques

KW - Complex Mixtures

KW - Crystallization

KW - Molecular Conformation

KW - Particle Size

KW - Solubility

KW - Solutions

KW - Solvents

KW - Sulfathiazoles

KW - Surface Properties

KW - Ultrafiltration

KW - Water

U2 - 10.1042/BA20040044

DO - 10.1042/BA20040044

M3 - Journal article

C2 - 15283678

VL - 41

SP - 17

EP - 28

JO - Biotechnology and Applied Biochemistry

JF - Biotechnology and Applied Biochemistry

SN - 0885-4513

IS - Pt 1

ER -