Biomedical subjects

Marjatta Louhi-Kultanen

Publications and source records attributed to Marjatta Louhi-Kultanen.

4 recordsLinked to original sources

PubMed2006

Solubility and stability of anhydrate/hydrate in solvent mixtures.

In this paper, the thermodynamics of the anhydrate/dihydrate carbamazepine (CBZA/CBZH) in ethanol-water mixtures was studied by measuring the solubility of anhydrate and dihydrate carbamazepine at 0-60 degrees C. Both stable form solubility and metastable form solubility were measured, the latter with the assistance of Raman immersion probe. The thermodynamic properties of the anhydrate/dihydrate system, such as the relative stability, and enthalpy and entropy of dissolution, were estimated by plotting the measured solubility data according to the van't Hoff equation. The anhydrate/dihydrate carbamazepine showed an enantiotropic relationship in the studied mixtures and temperature ranges. It was shown that at a certain temperature, there was an equilibrium water activity value at which the anhydrate and dihydrate carbamazepine were in equilibrium. This equilibrium water activity value depends significantly on the temperature. The lower the temperature, the smaller is the water activity value needed to attain equilibrium between anhydrate and dihydrate. The obtained results are useful in determining crystallization parameters to achieve a desired anhydrate or hydrate phase. The approach can be applied to other anhydrate and hydrate systems.

Carbamazepine↗

PubMed2006

Crystallization of glycine with ultrasound.

Sonocrystallization has proved to be an efficient tool to influence the external appearance and structure of a crystalline product obtained by various crystallization methods. The present work focuses on high intensity sonocrystallization of glycine by varying amplitude of ultrasound with an ultrasound frequency of 20kHz at two temperature ranges 40-50 and 20-30 degrees C in a jacketed 250-ml cooling crystallizer equipped with a stirrer. The polymorph composition of the obtained crystals was analyzed with a temperature variable X-ray powder diffractometer (XRPD). XRPD results showed that, besides the operating temperature, the glycine polymorphism was affected also by insonation. This was especially the case at the lower temperature range. Furthermore, based on the heat balance within the crystallizer, an increase in required cooling capacity was presented as a function of increasing ultrasound power. This study also showed, the higher the ultrasound amplitude the smaller the crystals obtained.

Chemistry, Pharmaceutical↗

PubMed2005

IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of crystallization process and solid-state analysis of crystalline product.

Crystalline product should exist in optimal polymorphic form. Robust and reliable method for polymorph characterization is of great importance. In this work, infra red (IR) spectroscopy is applied for monitoring of crystallization process in situ. The results show that attenuated total reflection Fourier transform infra red (ATR-FTIR) spectroscopy provides valuable information on process, which can be utilized for more controlled crystallization processes. Diffuse reflectance Fourier transform infra red (DRIFT-IR) is applied for polymorphic characterization of crystalline product using X-ray powder diffraction (XRPD) as a reference technique. In order to fully utilize DRIFT, the application of multivariate techniques are needed, e.g., multivariate statistical process control (MSPC), principal component analysis (PCA) and partial least squares (PLS). The results demonstrate that multivariate techniques provide the powerful tool for rapid evaluation of spectral data and also enable more reliable quantification of polymorphic composition of samples being mixtures of two or more polymorphs. This opens new perspectives for understanding crystallization processes and increases the level of safety within the manufacture of pharmaceutics.

Algorithms↗

PubMed2005

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 x 10(7))-(1.2 x 10(9)) m/kg].

1-Propanol↗