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Starogard Gdański, Poland

Tarnacka M.,University of Silesia | Kolodziejczyk K.,University of Silesia | Dulski M.,University of Silesia | Zakowiecki D.,Pharmaceutical Works Polpharma SA | And 5 more authors.
European Journal of Pharmaceutics and Biopharmaceutics

Different experimental and theoretical techniques were applied to investigate basic physical properties of very stable and homogeneous solid dispersions formed by itraconazole and octaacetylmaltose. Differential scanning calorimetry as well as semi-empirical calculations have indicated that liquid crystalline ordering in itraconazole was completely suppressed in the binary mixtures. Molecular dynamics studies with the use of broadband dielectric spectroscopy have shown that the width of the structural relaxation process becomes smaller and fragility drops in solid dispersions with respect to the pure itraconazole. Moreover, the dynamics of secondary relaxation processes was affected by acetylated maltose. As demonstrated, β- and γ-secondary modes shift to higher and lower frequencies, respectively. On the other hand, aging experiments revealed that isostructural relaxation times in the glassy state become systematically longer with the addition of modified carbohydrate. This is a very important finding in the context of the current discussion on the factors affecting physical stability of easily crystallizing APIs. It seems that beside intermolecular interactions and local reorientation, the global mobility might control the crystallization of amorphous solid dispersions. Finally, we have demonstrated that itraconazole in binary mixtures dissolves faster and to greater extent with respect to the crystalline and amorphous form of this API. © 2014 Elsevier B.V. All rights reserved. Source

Grzybowska K.,University of Silesia | Paluch M.,University of Silesia | Wlodarczyk P.,University of Silesia | Grzybowski A.,University of Silesia | And 6 more authors.
Molecular Pharmaceutics

In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification. © 2012 American Chemical Society. Source

Adrjanowicz K.,University of Silesia | Zakowiecki D.,Pharmaceutical Works Polpharma SA | Kaminski K.,University of Silesia | Hawelek L.,University of Silesia | And 5 more authors.
Molecular Pharmaceutics

Antibiotics are chemical compounds of extremely important medical role. Their history can be traced back more than one hundred years. Despite the passing time and significant progress made in pharmacy and medicine, treatment of many bacterial infections without antibiotics would be completely impossible. This makes them particularly unique substances and explains the unflagging popularity of antibiotics within the medical community. Herein, using dielectric spectroscopy we have studied the molecular mobility in the supercooled liquid and glassy states of three well-known antibiotic agents: azithromycin, clarithromycin and roxithromycin. Dielectric studies revealed a number of relaxation processes of different molecular origin. Besides the primary α-relaxation, observed above the respective glass transition temperatures of antibiotics, two secondary relaxations in the glassy state were identified. Interestingly, the fragility index as well as activation energies of the secondary processes turned out to be practically the same for all three compounds, indicating probably much the same molecular dynamics. Long-term stability of amorphous antibiotics at room temperature was confirmed by X-ray diffraction technique, and calorimetric studies were performed to evaluate the basic thermodynamic parameters. Finally, we have also checked the experimental solubility advantages given by the amorphous form of the examined antibiotics. © 2012 American Chemical Society. Source

Kaminski K.,University of Silesia | Adrjanowicz K.,University of Silesia | Zakowiecki D.,Pharmaceutical Works Polpharma SA | Kaminska E.,University of Silesia | And 4 more authors.
Molecular Pharmaceutics

Broadband dielectric measurements were carried out in the supercooled as well as in the glassy state of two very important disaccharides: trehalose and sucrose. Multiple relaxation processes were observed. Above the glass transition temperatures of examined disaccharides structural relaxation of cooperative origin was detected, where in the glassy state more local motions (secondary modes) appeared. Our data were discussed in light of the findings reported by other groups. We pointed out that sample preparation might impact mobility and, thus, dielectric loss spectra in a significant way. Consequently, it may lead to misinterpretation of the dielectric relaxation processes. Moreover, impact of physical aging and pressure on dynamics of two secondary relaxation processes observed in the glassy state of trehalose and sucrose has been investigated. Additionally, we have demonstrated that, in contrast to the calorimetric measurements (DSC), activation energies of the β- and γ-relaxation processes observed in the glassy state of sucrose and trehalose do not change as a result of physical aging. Finally, we found out that the β-relaxation process slows down as pressure increases. We interpreted this fact in view of increasing rigidity of the structures of disaccharides. © 2012 American Chemical Society. Source

Adrjanowicz K.,University of Silesia | Kaminski K.,University of Silesia | Grzybowska K.,University of Silesia | Hawelek L.,University of Silesia | And 7 more authors.
Pharmaceutical Research

Purpose: To investigate the effect of cryogrinding on chemical stability of the diuretic agent furosemide and its mixtures with selected excipients. Methods: Furosemide was ground at liquid nitrogen temperature for 30, 60, 120 and 180 min. Mixtures of furosemide-PVP and furosemide-inulin (1:1) were milled under cryogenic conditions. Materials were analyzed by XRD, UPLC, MS and NMR. Results: Upon increasing the milling time, a significant build-up of an unidentified impurity 1, probably the main degradation product, was noticed. Cogrinding of furosemide with PVP and inulin worsened chemical stabilization of the pharmaceutical. The main degradation product formed upon cryomilling was subsequently identified as 4-chloro-5-sulfamoylanthranilic acid (CSA). Based on some theoretical considerations involving specific milling conditions, the milling intensity and an expected specific milling dose have been calculated. Results indicate that cryogenic grinding is capable to initiate mechanically induced decomposition of furosemide. Conclusions: Cryogenic grinding can activate and accelerate not only structural changes (solid state amorphization) but also chemical decomposition of pharmaceuticals. A cryogenic milling device should be considered as a chemical reactor, where under favourable conditions chemical reactions could be mechanically initiated. © 2011 The Author(s). Source

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