19 results on '"Jukka Rantanen"'
Search Results
2. Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy
- Author
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Niklas Nilsson, Katerina Nezvalova-Henriksen, Johan P. Bøtker, Niels Højmark Andersen, Bjarke Strøm Larsen, Jukka Rantanen, Ingunn Tho, and Jørgen Brustugun
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Intravenous drugs are often co-administrated in the same intravenous catheter line due to which compatibility issues, such as complex precipitation processes in the catheter line, may occur. A well-known example that led to several neonatal deaths is the precipitation due to co-administration of ceftriaxone- and calcium-containing solutions. The current study is exploring the applicability of Raman spectroscopy for testing intravenous drug compatibility in hospital settings. The precipitation of ceftriaxone calcium was used as a model system and explored in several multi-drug mixtures containing both structurally similar and clinically relevant drugs for co-infusion. Equal molar concentrations of solutions containing ceftriaxone and calcium chloride dihydrate were mixed with solutions of cefotaxime, ampicillin, paracetamol, and metoclopramide. The precipitate formed was collected as an "unknown" material, dried, and analyzed. Several solid-state analytical methods, including X-ray powder diffraction, Raman spectroscopy, and thermogravimetric analysis, were used to characterize the precipitate. Raman microscopy was used to investigate the identity of single sub-visual particles precipitated from a mixture of ceftriaxone, cefotaxime, and calcium chloride. X-ray powder diffraction suggested that the precipitate was partially crystalline; however, the identity of the solid form of the precipitate could not be confirmed with this standard method. Raman spectroscopy combined with multi-variate analyses (principal component analysis and soft independent modelling class analogy) enabled the correct detection and identification of the precipitate as ceftriaxone calcium. Raman microscopy enabled the identification of ceftriaxone calcium single particles of sub-visual size (around 25 μm), which is in the size range that may occlude capillaries. This study indicates that Raman spectroscopy is a promising approach for supporting clinical decisions and especially for compatibility assessments of drug infusions in hospital settings.
- Published
- 2023
3. Effect of pH on the Surface Layer of Molecular Crystals at the Solid–Liquid Interface
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Mikkel Herzberg, Anders S. Larsen, Tue Hassenkam, Anders Ø. Madsen, and Jukka Rantanen
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Drug Discovery ,Biological Availability ,Water ,Pharmaceutical Science ,Molecular Medicine ,Hydrogen-Ion Concentration ,Crystallization ,Microscopy, Atomic Force - Abstract
Dissolution of solid matter into aqueous solution is one of the most challenging physicochemical aspects related to drug development. While influenced by several parameters, the effect of pH remains the most important one to be fully understood. The dissolution process is essentially controlled by activity at the surface of the molecular crystals, which is difficult to characterize experimentally. To address this, a combination of
- Published
- 2022
4. Elucidating the Dehydration Mechanism of Nitrofurantoin Monohydrate II Using Low-Frequency Raman Spectroscopy
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Peter III J. G. Remoto, Ka̅rlis Be̅rziņš, Sara J. Fraser-Miller, Timothy M. Korter, Thomas Rades, Jukka Rantanen, and Keith C. Gordon
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General Materials Science ,General Chemistry ,Condensed Matter Physics - Published
- 2022
5. Monitoring the Isothermal Dehydration of Crystalline Hydrates Using Low-Frequency Raman Spectroscopy
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Keith C. Gordon, Chima Robert, Peter Ouma Okeyo, Ka Rlis Be Rziņš, Jukka Rantanen, Sara J. Fraser-Miller, and Thomas Rades
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Materials science ,Analytical chemistry ,Pharmaceutical Science ,02 engineering and technology ,Low frequency ,Spectrum Analysis, Raman ,Piroxicam ,030226 pharmacology & pharmacy ,Isothermal process ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Theophylline ,Drug Discovery ,medicine ,Dehydration ,Spectroscopy ,Temperature ,021001 nanoscience & nanotechnology ,medicine.disease ,Pharmaceutical Preparations ,symbols ,Molecular Medicine ,Crystallization ,0210 nano-technology ,Raman spectroscopy ,medicine.drug - Abstract
Detection of the solid-state forms of pharmaceutical compounds is important from the drug performance point of view. Low-frequency Raman (LFR) spectroscopy has been demonstrated to be very sensitive in detecting the different solid-state forms of pharmaceutically relevant compounds. The potential of LFR spectroscopy to probe the in situ isothermal dehydration was studied using piroxicam monohydrate (PXM) and theophylline monohydrate (TPMH) as the model drugs. The dehydration of PXM and TPMH at four different temperatures (95, 100, 105, and 110 °C and 50, 60, 70, and 80 °C, respectively) was monitored in both the low- (20-300 cm
- Published
- 2021
6. Improving Powder Characteristics by Surface Modification Using Atomic Layer Deposition
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Johan Boetker, Steven M. George, Cosima Hirschberg, Jukka Rantanen, Nikolaj Sølvkær Jensen, Changquan Calvin Sun, Jens Risbo, Pekka Hoppu, Tommi Kääriäinen, Marja-Leena Kääriäinen, Matti Murtomaa, and Anders Ø. Madsen
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Atomic layer deposition ,Materials science ,Primary (chemistry) ,Chemical engineering ,010405 organic chemistry ,Organic Chemistry ,Surface modification ,Physical and Theoretical Chemistry ,Particulates ,010402 general chemistry ,Particle coating ,01 natural sciences ,0104 chemical sciences - Abstract
The particulate properties of a material after primary manufacturing have a large impact on the secondary manufacturing processes. Especially, powder characteristics leading to poor flowability are...
- Published
- 2019
7. Insight into Nanoscale Network of Spray-Dried Polymeric Particles: Role of Polymer Molecular Conformation
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Mingshi Yang, Jukka Rantanen, Feng Wan, Flemming H. Larsen, Camilla Foged, and Heloisa N. Bordallo
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Magnetic Resonance Spectroscopy ,Materials science ,Polymers ,Molecular Conformation ,Supramolecular chemistry ,macromolecular substances ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Acetone ,chemistry.chemical_compound ,Drug Delivery Systems ,Polylactic Acid-Polyglycolic Acid Copolymer ,Scattering, Radiation ,Molecule ,General Materials Science ,Neutrons ,chemistry.chemical_classification ,Principal Component Analysis ,Viscosity ,Methanol ,technology, industry, and agriculture ,Rational design ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,PLGA ,Solid-state nuclear magnetic resonance ,Chemical engineering ,chemistry ,Spray drying ,Solvents ,Nanoparticles ,Particle ,0210 nano-technology - Abstract
Poly(lactic- co-glycolic acid) (PLGA) microparticles represent a promising formulation approach for providing steady pharmacokinetic/pharmacodynamic profiles of therapeutic drugs for a long period. Understanding and controlling the supramolecular structure of PLGA microparticles at a molecular level is a prerequisite for the rational design of well-controlled, reproducible sustained-release profiles. Herein, we reveal the role of PLGA molecular conformation in particle formation and drug release. The nanoscale network of PLGA microparticles spray-dried using the solvents with distinct polarities was investigated by using NMR and neutron scattering. By employing chemometric method, we further demonstrate the evolution of nanoscale networks in spray-dried PLGA microparticles upon water absorption. Our results indicate that PLGA molecules form more chain entanglements during spray drying when using the solvents with low polarity, where PLGA molecule adopts a more flexible, extended conformation, resulting in the network being more resistant to water absorption in spray-dried PLGA microparticles. This work underlines the role of PLGA molecular conformation in controlling formation and evolution of nanoscale network of spray-dried PLGA microparticles and will have important consequences in achieving customized drug release from the PLGA microparticles.
- Published
- 2018
8. Dehydration of Nitrofurantoin Monohydrate during Melt Extrusion
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Jukka Rantanen, Andrew D. Bond, Dhara Raijada, Niklas Sandler, Johanna Aho, Lærke Arnfast, and Johan Bøtker
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Thermogravimetric analysis ,Materials science ,Rheometry ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,030226 pharmacology & pharmacy ,Dosage form ,03 medical and health sciences ,Crystallography ,0302 clinical medicine ,Differential scanning calorimetry ,Chemical engineering ,Polymer ratio ,Nitrofurantoin Monohydrate ,medicine ,General Materials Science ,Extrusion ,Dehydration ,0210 nano-technology - Abstract
Hot melt extrusion is important for the development of advanced pharmaceutical dosage forms. In this study, the dehydration of nitrofurantoin monohydrate during melt extrusion below the expected dehydration temperature has been investigated. The influence of process time, temperature, and drug/polymer ratio on the solid form of the drug compound was studied using drug/polymer physical mixtures with thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction, rheometry, and hot-stage microscopy and compared with data generated from the extruded products. Extensive dehydration of nitrofurantoin monohydrate was surprisingly observed at extrusion temperatures as low as 70 °C in contrast with TGA and DSC analysis of the pure drug indicating dehydration onset at around 90 °C. This was related to shear induced solution-mediated transformation, where nitrofurantoin dissolved into the molten polymer and rapidly recrystallized as nitrofurantoin anhydrate, as well as simultane...
- Published
- 2017
9. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient
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Andrew D. Bond, Christian R. Parker, Pratik P. Upadhyay, Jukka Rantanen, Nawin Pudasaini, and Stefan U. Hagen
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Active ingredient ,Materials science ,Downstream processing ,Organic Chemistry ,Context (language use) ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Compression (physics) ,030226 pharmacology & pharmacy ,Volumetric flow rate ,Shear (sheet metal) ,03 medical and health sciences ,0302 clinical medicine ,Downstream (manufacturing) ,Physical and Theoretical Chemistry ,Composite material ,Crystal habit ,0210 nano-technology - Abstract
Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, elongated hexagons, and spheroids) in the context of direct compression using ring shear tester, flow rate analyzer, and instrumented tablet press. As expected, needles were very cohesive, had low flow rate (1.0 ± 0.08 mg/s), and low bulk density (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite w...
- Published
- 2017
10. Insights into the Early Dissolution Events of Amlodipine Using UV Imaging and Raman Spectroscopy
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Jukka Rantanen, Claus Cornett, Vishal Koradia, Marja Savolainen, Fang Tian, Anette Müllertz, Johan Boetker, Thomas Rades, and Jesper Østergaard
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Magnetic Resonance Spectroscopy ,Materials science ,Molecular Structure ,Analytical chemistry ,Pharmaceutical Science ,Spectrum Analysis, Raman ,Amorphous solid ,symbols.namesake ,Solubility ,Chemical engineering ,Thermogravimetry ,Drug Discovery ,Drug release ,symbols ,medicine ,Molecular Medicine ,Spectrophotometry, Ultraviolet ,Dissolution testing ,Amlodipine ,Raman spectroscopy ,Dissolution ,medicine.drug - Abstract
Traditional dissolution testing determines drug release to the bulk, but does not enable an understanding of the events happening close to the surface of a solid or a tablet. UV imaging is a new imaging approach that can be used to study the dissolution behavior of chemical compounds. The UV imaging instrumentation offers recording of absorbance maps with a high spatial and temporal resolution which facilitates the abundant collection of information regarding the evolving solution concentrations. In this study, UV imaging was used to visualize the dissolution behavior of amlodipine besylate (amorphous and dihydrate forms) and amlodipine free base. The dissolution of amlodipine besylate was faster from the amorphous form than from the crystalline forms. The UV imaging investigations suggested that a solvent mediated phase transformation occurred for the amorphous amlodipine besylate and the amlodipine free base samples. Raman spectroscopy was used to confirm and probe the changes at the solid surface occurring upon contact with the dissolution media and verified the recrystallization of the amorphous form to the monohydrate. The combination of UV imaging and Raman spectroscopy is an efficient tool to obtain a deeper insight into the early events of the dissolution process.
- Published
- 2011
11. Effects of Polymer Additives on the Crystallization of Hydrates: A Molecular-Level Modulation
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Stefania Baldursdottir, Jukka Rantanen, and Fang Tian
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Models, Molecular ,Ethylene ,Materials science ,Nitrofurans ,Polymers ,Pharmaceutical Science ,law.invention ,chemistry.chemical_compound ,Molecular level ,X-Ray Diffraction ,law ,Spectroscopy, Fourier Transform Infrared ,Drug Discovery ,PEG ratio ,Polymer chemistry ,Crystallization ,chemistry.chemical_classification ,Molecular Structure ,Viscosity ,Hydrogen bond ,technology, industry, and agriculture ,Water ,Polymer ,Solutions ,chemistry ,Modulation ,Molecular Medicine ,Rheology ,Hydrate - Abstract
The purpose of this study is to elucidate the effects of polymer additives on the growth behavior and final internal structure of hydrate crystals. The polymers used were poly(ethylene) glycol (PEG), ethyl(hydroxyethyl) cellulose (EHEC) and hydroxylpropyl methylcellulose (HPMC). Rheological characterization of the polymer solutions was carried out. Nitrofurantoin and carbamazepine were crystallized separately from a mixture of acetone and polymer/water solution through evaporative crystallization. The crystallization process and final crystals were characterized by light microscopy, XRPD and FT-IR spectroscopy. PEG showed a minor viscosity increase, but polymer network associations were found in the EHEC and HPMC solutions. With no additive, nitrofurantoin crystallized as a mixture of plate-like (monohydrate I) and needle-like (monohydrate II) crystals. All polymers affected the crystalline phase, and HPMC and EHEC also changed the crystal morphology from needle-like to dendrite-like. H-Bonding was found to exist between these polymers (O-H group) and nitrofurantoin monohydrate (CO== group), while this was not the case with carbamazepine hydrate. Additives were able to modify the crystal phase and morphology due to H-bonding and polymer network properties. We envisage that the improved understanding of additives' role provided by this study can be utilized when designing control strategies for the crystallization process.
- Published
- 2008
12. Near-Infrared Spectroscopy for Cocrystal Screening. A Comparative Study with Raman Spectroscopy
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Jukka Rantanen, Claus Cornett, Sitaram P. Velaga, Morten Allesø, Heidi Lopez de Diego, Frans van den Berg, Morten Arendt Rasmussen, and Amjad Alhalaweh
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Aspartic Acid ,Spectrophotometry, Infrared ,medicine.diagnostic_test ,Chemistry ,Indomethacin ,Near-infrared spectroscopy ,Analytical chemistry ,Spectrum Analysis, Raman ,Cocrystal ,Analytical Chemistry ,law.invention ,symbols.namesake ,Saccharin ,X-Ray Diffraction ,law ,Spectrophotometry ,Phase (matter) ,medicine ,symbols ,Molecule ,Crystallization ,Raman spectroscopy ,Spectroscopy ,Nuclear chemistry - Abstract
Near-infrared (NIR) spectroscopy is a well-established technique for solid-state analysis, providing fast, noninvasive measurements. The use of NIR spectroscopy for polymorph screening and the associated advantages have recently been demonstrated. The objective of this work was to evaluate the analytical potential of NIR spectroscopy for cocrystal screening using Raman spectroscopy as a comparative method. Indomethacin was used as the parent molecule, while saccharin and l-aspartic acid were chosen as guest molecules. Molar ratios of 1:1 for each system were subjected to two types of preparative methods. In the case of saccharin, liquid-assisted cogrinding as well as cocrystallization from solution resulted in a stable 1:1 cocrystalline phase termed IND-SAC cocrystal. For l-aspartic acid, the solution-based method resulted in a polymorphic transition of indomethacin into the metastable alpha form retained in a physical mixture with the guest molecule, while liquid-assisted cogrinding did not induce any changes in the crystal lattice. The good chemical peak selectivity of Raman spectroscopy allowed a straightforward interpretation of sample data by analyzing peak positions and comparing to those of pure references. In addition, Raman spectroscopy provided additional information on the crystal structure of the IND-SAC cocrystal. The broad spectral line shapes of NIR spectra make visual interpretation of the spectra difficult, and consequently, multivariate modeling by principal component analysis (PCA) was applied. Successful use of NIR/PCA was possible only through the inclusion of a set of reference mixtures of parent and guest molecules representing possible solid-state outcomes from the cocrystal screening. The practical hurdle related to the need for reference mixtures seems to restrict the applicability of NIR spectroscopy in cocrystal screening.
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- 2008
13. Hydroxypropyl Methylcellulose-Controlled Crystallization of Erythromycin A Dihydrate Crystals with Modified Morphology
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Osmo Antikainen, Jukka Rantanen, Jouko Yliruusi, Heikki Vuorela, Pia Vuorela, Sabiruddin Mirza, Inna Miroshnyk, and Jyrki Heinämäki
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Active ingredient ,Chemistry ,technology, industry, and agriculture ,Erythromycin ,General Chemistry ,Condensed Matter Physics ,Recrystallization (chemistry) ,Crystal engineering ,law.invention ,Crystal ,Crystallography ,law ,medicine ,General Materials Science ,Crystallization ,Crystal habit ,Nuclear chemistry ,medicine.drug - Abstract
Crystallization in the presence of pharmaceutically accepted excipients as additives was investigated as a tool for morphological crystal engineering of active pharmaceutical ingredients. Recrystallization of a model drug substance, erythromycin A dihydrate, was carried out by a precipitation technique in the presence of varying amount of hydroxypropyl methylcellulose (HPMC). In contrast to the reference crystals, the crystals grown in the presence of HPMC exhibited regular shape, which varied with the concentration of the additive present, thus indicating that HPMC is an effective habit modifier for erythromycin A dihydrate. On the basis of the crystal surface chemistry, the mechanism responsible for the change in morphology is proposed. Finally, the effect of crystal habit modification on compaction behavior of erythromycin A dihydrate is demonstrated.
- Published
- 2008
14. Toward an Understanding of the Factors Influencing Anhydrate-to-Hydrate Transformation Kinetics in Aqueous Environments
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Lynne S. Taylor, Håkan Wikström, Alan D. Gift, and Jukka Rantanen
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Aqueous solution ,Chemistry ,Clathrate hydrate ,Mineralogy ,General Chemistry ,Condensed Matter Physics ,Chemical engineering ,Phase (matter) ,Anhydrous ,General Materials Science ,Growth rate ,Solubility ,Hydrate ,Dissolution - Abstract
Approximately one-third of all drugs can form hydrates, and therefore an in-depth understanding of the factors affecting anhydrate-to-hydrate transformation kinetics in a variety of environments is of interest. In this work, real-time analytical methods, in the form of Raman spectroscopy and optical microscopy, were used to establish representative transformation profiles and growth kinetics for hydrate formation of several drug substances. By comparing and contrasting the behavior of these different hydrates in terms of their specific properties such as solubility, dissolution rate, and growth rate of hydrate phase, and the influence of external factors such as seeding and agitation conditions, an increased understanding of hydrate formation has been achieved. The overall transformation rate from anhydrous to hydrate form was found to be not only a function of compound-specific properties, but was also strongly affected by surface properties and external factors such as the presence of seeds and the degr...
- Published
- 2008
15. Implementation of a Process Analytical Technology System in a Freeze-Drying Process Using Raman Spectroscopy for In-Line Process Monitoring
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Jukka Rantanen, Morten Allesø, H Lopez De Diego, T. De Beer, Jean Paul Remon, A Coppens, W R G Baeyens, Y. Vander Heyden, Chris Vervaet, F Goethals, and Francis Verpoort
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Spectroscopy, Near-Infrared ,Chemistry ,Process analytical technology ,Nucleation ,Analytical chemistry ,Sodium Chloride ,Spectrum Analysis, Raman ,Sensitivity and Specificity ,Analytical Chemistry ,law.invention ,Solutions ,Freeze-drying ,symbols.namesake ,Freeze Drying ,law ,Scientific method ,symbols ,Mannitol ,Sublimation (phase transition) ,Crystallization ,Spectroscopy ,Raman spectroscopy ,Powder Diffraction - Abstract
The aim of the present study was to propose a strategy for the implementation of a Process Analytical Technology system in freeze-drying processes. Mannitol solutions, some of them supplied with NaCl, were used as models to freeze-dry. Noninvasive and in-line Raman measurements were continuously performed during lyophilization of the solutions to monitor real time the mannitol solid state, the end points of the different process steps (freezing, primary drying, secondary drying), and physical phenomena occurring during the process. At-line near-infrared (NIR) and X-ray powder diffractometry (XRPD) measurements were done to confirm the Raman conclusions and to find out additional information. The collected spectra during the processes were analyzed using principal component analysis and multivariate curve resolution. A two-level full factorial design was used to study the significant influence of process (freezing rate) and formulation variables (concentration of mannitol, concentration of NaCl, volume of freeze-dried sample) upon freeze-drying. Raman spectroscopy was able to monitor (i) the mannitol solid state (amorphous, alpha, beta, delta, and hemihydrate), (ii) several process step end points (end of mannitol crystallization during freezing, primary drying), and (iii) physical phenomena occurring during freeze-drying (onset of ice nucleation, onset of mannitol crystallization during the freezing step, onset of ice sublimation). NIR proved to be a more sensitive tool to monitor sublimation than Raman spectroscopy, while XRPD helped to unravel the mannitol hemihydrate in the samples. The experimental design results showed that several process and formulation variables significantly influence different aspects of lyophilization and that both are interrelated. Raman spectroscopy (in-line) and NIR spectroscopy and XRPD (at-line) not only allowed the real-time monitoring of mannitol freeze-drying processes but also helped (in combination with experimental design) us to understand the process.
- Published
- 2007
16. Solvent-Mediated Phase Transformation Kinetics of an Anhydrate/Hydrate System
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Haiyan Qu, Jukka Rantanen, Juha Kallas, and Marjatta Louhi-Kultanen
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Supersaturation ,Aqueous solution ,Chemistry ,Stereochemistry ,Thermodynamics ,General Chemistry ,Condensed Matter Physics ,law.invention ,Solvent ,law ,Phase (matter) ,General Materials Science ,Solubility ,Crystallization ,Solvent effects ,Hydrate - Abstract
In-line monitoring of solid-state properties in crystallization processes is of great significance in controlling the quality of crystalline active pharmaceutical ingredients. In this work, the solvent-mediated phase transformation of anhydrous to dihydrated carbamazepine in ethanol−water mixtures was studied using an in-line Raman immersion probe. The solute concentration profile was measured by off-line sampling. The transformation experiments were conducted with different operation parameters in terms of solvent composition and temperature. The transformation rate depends on both solvent composition and temperature. The mechanism of the transition was interpreted with the two-step polymorphic form transformation mechanism. It was observed that the crystallization of the stable form was the rate-controlling step. The influence of the operation parameters on the transformation rate can be interpreted as the effects of solvent and supersaturation on the crystallization kinetics. Another interpretation is ...
- Published
- 2006
17. Insight into Thermally Induced Phase Transformations of Erythromycin A Dihydrate
- Author
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Jouko Yliruusi, Jukka Rantanen, Inna Miroshnyk, Leonid Khriachtchev, Jyrki Heinämäki, and Sabiruddin Mirza
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Phase transition ,Reaction mechanism ,Chemistry ,Stereochemistry ,Crystal chemistry ,Erythromycin ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,030226 pharmacology & pharmacy ,Bulk drug ,Dosage form ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Chemical engineering ,medicine ,symbols ,General Materials Science ,Dehydration ,0210 nano-technology ,Raman spectroscopy ,medicine.drug - Abstract
Thermal stress that pharmaceutical solids are exposed to during manufacturing can induce various phase transitions in bulk drug substances or excipients, resulting in altered dosage form performance. This paper reports on the thermally induced transformations of a macrolide antibiotic, erythromycin A dihydrate, investigated in situ by variable temperature powder X-ray diffractometry and hot-stage Raman spectroscopy. Erythromycin A dihydrate undergoes dehydration to isomorphic dehydrate, which then melts and recrystallizes to anhydrate. Raman spectroscopy was able to distinguish the two isomorphs of erythromycin A, the dihydrate and the dehydrate, thus offering a potential tool for in-process control of the drying process. The model fitting approach did not provide insight into the solid-state dehydration mechanism. However, the reaction mechanism was presented on the basis of crystal chemistry.
- Published
- 2005
18. Use of In-Line Near-Infrared Spectroscopy in Combination with Chemometrics for Improved Understanding of Pharmaceutical Processes
- Author
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Rebecca Turner, Håkan Wikström, Lynne S. Taylor, and Jukka Rantanen
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Quality Control ,High Shear Granulation ,Analytical chemistry ,Mixing (process engineering) ,02 engineering and technology ,01 natural sciences ,Analytical Chemistry ,Chemometrics ,Granulation ,Technology, Pharmaceutical ,Mannitol ,Particle Size ,Cellulose ,Process engineering ,Spectroscopy, Near-Infrared ,business.industry ,Chemistry ,Homogeneity (statistics) ,010401 analytical chemistry ,021001 nanoscience & nanotechnology ,Unit operation ,0104 chemical sciences ,Shear (sheet metal) ,Multivariate Analysis ,Principal component analysis ,0210 nano-technology ,business - Abstract
High shear granulation is a complex unit operation with several interacting process parameters. No generally accepted real-time in-line tools are available to gain insight into this process, and in practice, a highly experienced process formulator and operator are needed to develop a wet granulated solid dosage form. In this study, the use of in-line near-infrared (NIR) spectroscopy as a process analytical tool for high shear granulation was investigated. In combination with principal component-based methods, process analysis of three separate phases of high shear wet granulation (mixing, spraying, and wet massing) was facilitated. Critical information, both chemical and physical, was collected during processing. Chemical information included the homogeneity of the formulation and the amount of water in wet mass. In addition, physical information related to the particle size of granules was extracted. Principal component loadings were fully interpreted to validate the conclusions drawn from scores and predictions. Thus NIR spectroscopy could be used to determine the end points of the three subphases of high shear wet granulation and, as such, provide a fast in-line quality control tool.
- Published
- 2004
19. Polymorph Screening Using Near-Infrared Spectroscopy
- Author
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T. Paulus Seitavuopio, Jaakko Aaltonen, Marja Savolainen, Simo Siiriä, Jukka Rantanen, Anna Cecilia Jørgensen, Niklas Laitinen, Marjatta Louhi-Kultanen, Milja Karjalainen, and Jouko Yliruusi
- Subjects
Crystallinity ,Polymorphism (materials science) ,Chemistry ,Near-infrared spectroscopy ,X-ray crystallography ,Analytical chemistry ,Thermal analysis ,Spectroscopy ,Ball mill ,Powder diffraction ,Analytical Chemistry - Abstract
Near-infrared spectroscopy was utilized as a polymorph screening method. A model compound (sulfathiazole) was recrystallized from various solvents, and the crystals were milled using a planetary ball mill and compressed using a hydraulic press. The polymorphism of recrystallized and processed samples and the effect of processing on the polymorphism of sulfathiazole was studied by near-infrared (NIR) spectroscopy and verified by X-ray powder diffraction (XRPD) and thermal analysis. Polymorphism and the degree of crystallinity of the processed samples were studied, and NIR spectroscopy proved to be a fast tool for polymorph screening and monitoring the processing-induced transformations. After clustering of the NIR spectra of various samples, XRPD and complementary methods can be applied to a more thorough analysis of different clusters. This approach provides a timesaving improvement for the polymorph analysis in the case of large number of samples.
- Published
- 2003
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