Kati Pöllänen

Establishing quantitative in-line analysis of multiple solid-state transformations during dehydration

The aim of the study was to conduct quantitative solid phase analysis of piroxicam (PRX) and carbamazepine (CBZ) during isothermal dehydration in situ, and additionally exploit the constructed quantitative models to analyze the solid-state forms in-line during fluidized bed drying. Vibrational spectroscopy (near-infrared (NIR), Raman) was employed for monitoring the dehydration and the quantitative model was based on partial least squares (PLS) regression. PLS quantification was confirmed experimentally using isothermal thermogravimetric analysis (TGA) and X-ray powder diffractometry (XRPD). To appraise the quality of quantitative models several model parameters were evaluated. The hot-stage spectroscopy quantification results were found to be in reasonable agreement with TGA and XRPD results. Quantification of PRX forms showed complementary results with both spectroscopic techniques. The solid-state forms observed during CBZ dihydrate dehydration were quantified with Raman spectroscopy, but NIR spectroscopy failed to differentiate between the anhydrous solid-state forms of CBZ. In addition to in situ dehydration quantification, Raman spectroscopy in combination with PLS regression enabled in-line analysis of the solid-state transformations of CBZ during dehydration in a fluidized bed dryer.

An insight into water of crystallization during processing using vibrational spectroscopy

Many organic molecules used as drugs can incorporate water into their crystal lattice. These compounds are also prone to processing-induced transformations (PITs) because processing often exposes the compounds to moisture, heat and mechanical stress. The aim of this review is to provide an overview of the possibilities for following and understanding hydrate/anhydrate transformations using vibrational spectroscopy (mid-infrared, near-infrared, Raman and terahertz). The review begins with a general section on hydrates, followed by considerations on the impact of these on drug products and a description of transformation mechanisms of hydrates. Moreover, a general introduction is given for the spectroscopic techniques together with a discussion of critical issues for quantification models. Unit operations that may induce transformations in hydrate systems are discussed with focus on the published work on the use of spectroscopy to derive information from these processes. Finally, the effect of excipients on PITs is discussed.

Batch cooling crystallization and pressure filtration of sulphathiazole: The influence of solvent composition

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 [(8.7×107)–(1.2×109) m/kg].