Browsing by Subject "crystallization"

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  • Mah, Pei T.; Novakovic, Dunja; Saarinen, Jukka; Landeghem, Stijn Van; Peltonen, Leena; Laaksonen, Timo; Isomäki, Antti; Strachan, Clare J. (2017)
    Purpose To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods. Method Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy. Results Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage. Conclusion SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.
  • Savelainen, Timo (Helsingfors universitet, 2013)
    Some problems in dry powder inhaler formulation include low dose efficiency and changes in dispersibility during storage. For lung deposition particles should have aerodynamic size of 1 - 5µm. Poor dispersion of drug particles from carriers' surface is thought to be the main reason for low dose efficacy. A tertiary component of small particles has been generally added to formulation to improve fine particle dose. Small particles are usually manufactured by micronization. This may induce crystal defects and amorphous sites on the surface of crystals. Amorphous sites are metastable and they may crystallize during storing. Changes in particles crystallinity may have an action on efficiency and stability of dry powder inhalers. Conditioning is designated as stabilisation of particles surface by mixture of solvent vapour and inert gas. Vapour may also dissolve surface roughness. This is called deliquescence. Ostwald ripening is phenomenon whereby small particles dissolves and recrystallizes onto larger crystals. This can be extended for surface asperities. Amorphous materials have also better solubility than crystalline materials so amorphous sites may also dissolve and recrystallize onto crystalline surface. Amorphous sites may crystallize spontaneously by absorbing plasticizing agents from vapour phase or by influence of temperature. The purpose of this work was to study process variables in conditioning and their effect on modification of surface roughness and stabilization of micronized α-lactose monohydrate and test drug substance. The purpose was also to study how surface modification and stabilization effects on powders flowability and stability of dry powder inhaler. The dry powder inhaler contained two different vicinity of lactose and two different drug substances. Conditioning was based on evaporation of liquid from open surface. Studied process variables were temperature of powder, temperature of bath of liquid phase and flow rate of nitrogen gas. The aim of this study was to form a process design for conditioning of new substances, to improve powders flowability and to remove changes in fine particle dose during storage. Surface roughness was studied by laser diffraction analysis and specific surface area measurements and also by electron microscopy. Specific surface area was measured by nitrogen adsorption method. Stabilization of amorphous sites ware studied by dynamic vapour sorption. Flowability was measured by angle of repose and with FlowPro device. Fine particle dose was measured with next generator impactor device. The study showed that increasing the amount of solvent in vapour increases surface smoothness and stabilization. Also increase of temperature of sample increased stabilization. Influence of temperature on surface smoothness was not as clear. Changes in temperature may have altered adsorption and kinetic of crystallization of dissolved molecules. Flowability of lactose was significantly improved. Condition did not improve dry powder inhalers fine particle dose, but there was significant difference between different process conditions. This was concluded to be caused of surface modification. It was also shown that different process conditions affected on formulations stability.
  • Nordberg, Antti (Helsingfors universitet, 2011)
    Nearly one fourth of new medicinal molecules are biopharmaceutical (protein, antibody or nucleic acid derivative) based. However, the administration of these compounds is not always that straightforward due to the fragile nature of aforementioned domains in GI-tract. In addition, these molecules often exhibit poor bioavailability when administered orally. As a result, parenteral administration is commonly preferred. In addition, shelf-life of these molecules in aqueous environments is poor, unless stored in low temperatures. Another approach is to bring these molecules to anhydrous form via lyophilization resulting in enhanced stability during storage. Proteins cannot most commonly be freeze dried by themselves so some kind of excipients are nearly always necessary. Disaccharides are commonly utilized excipients in freeze-dried formulations since they provide a rigid glassy matrix to maintain the native conformation of the protein domain. They also act as "sink"-agents, which basically mean that they can absorb some moisture from the environment and still help to protect the API itself to retain its activity and therefore offer a way to robust formulation. The aim of the present study was to investigate how four amorphous disaccharides (cellobiose, melibiose, sucrose and trehalose) behave when they are brought to different relative humidity levels. At first, solutions of each disaccharide were prepared, filled into scintillation vials and freeze dried. Initial information on how the moisture induced transformations take place, the lyophilized amorphous disaccharide cakes were placed in vacuum desiccators containing different relative humidity levels for defined period, after which selected analyzing methods were utilized to further examine the occurred transformations. Affinity to crystallization, water sorption of the disaccharides, the effect of moisture on glass transition and crystallization temperature were studied. In addition FT-IR microscopy was utilized to map the moisture distribution on a piece of lyophilized cake. Observations made during the experiments backed up the data mentioned in a previous study: melibiose and trehalose were shown to be superior over sucrose and cellobiose what comes to the ability to withstand elevated humidity and temperature, and to avoid crystallization with pharmaceutically relevant moisture contents. The difference was made evident with every utilized analyzing method. In addition, melibiose showed interesting anomalies during DVS runs, which were absent with other amorphous disaccharides. Particularly fascinating was the observation made with polarized light microscope, which revealed a possible small-scale crystallization that cannot be observed with XRPD. As a result, a suggestion can safely be made that a robust formulation is most likely obtained by utilizing either melibiose or trehalose as a stabilizing agent for biopharmaceutical freeze-dried formulations. On the other hand, more experiments should be conducted to obtain more accurate information on why these disaccharides have better tolerance for elevating humidities than others.
  • Markkanen, Minna (Helsingin yliopisto, 2021)
    The orbicular quartz monzonite from Kuohenmaa, Southwest Finland, is one of the most beautiful and well-known orbicular rocks in the world. The cores of the orbicules are peraluminous in composition, most likely of xenolithic metasedimentary origin. The cores are surrounded by orbicule mantles, which consist of several alternating biotite- and plagioclase-rich shells. There are three types of orbicules in Kuohenmaa orbicular rock: proto-, small-, and large-orbicular types. Proto-orbicules have only a few shells, small orbicules ~ 50 shells in average, and large orbicules over 250 distinct shells. In addition to shells, one sample was observed to be associated with comb layering in the contact of proto-orbicular and large orbicular types. Structures and textures of the comb layer resembles those of the outer shells of large orbicules. The orbicules are embedded in interstitial coarse-grained groundmass that forms locally almost pegmatitic patches. The petrographic observations were acquired from eight samples or sample photographs gathered from different collections. A mineral chemistry dataset was measured from a single large orbicule from the University of Helsinki collections. The main minerals of the Kuohenmaa orbicular rock are plagioclase, biotite, microcline, muscovite, and chlorite. The shell textures vary from branching plagioclase-rich shells to fine-grained plagioclase- or biotite-rich shells. Branching shells are mainly oligoclase, but a few granular andesine crystals were detected in the core. Peculiar interstitial fibrous allanite masses were found in the inner branching plagioclase-rich shells. The plagioclase compositions generally follow a regular fractional crystallization trend from core to groundmass, but some changes towards more primary compositions are observed in the orbicule mantle. Plagioclase crystals display only minor compositional zoning, suggesting rather quick crystallization. Biotite is very aluminous (Al2O3 17.63–18.53) in composition, and the compositional changes seem to have somewhat positive correlation with plagioclase compositions, suggesting changes in their crystallization conditions. Injections of primary melt from a deeper source most likely caused the observed changes to more primitive composition in plagioclase and biotite composition. Through the detailed petrographic and geochemical studies, a model of undercooling caused by decompression driven fluid saturation is proposed as a mechanism for orbicule formation in the Kuohenmaa orbicular rock. Branching plagioclase with interstitial fibrous allanite masses and several fluid inclusions in plagioclase indicates separate aqueous REE-enriched melt and rapid crystallization. Further studies of fluid inclusions and REE-enriched phases could provide information of the fluid origin and crystallization conditions.
  • Tallberg, Linda (Svenska handelshögskolan, 2014)
    Economics and Society – 270
    This book is about life at an Australian animal shelter, called ANIMA. The shelter is tasked with organizing the dark side of humanity of cruelty, neglect, and ignorance. It is about the humans and animals who live and die in the organization - often silenced and hidden in society. Employees join the organization to save animals, yet due to organizational constraints, are the ones who are tasked with the killing. In ANIMA, the emotional and moral conflict is both constant and intense for animal shelter employees. They are promotivated and have strong ideological alignment to the organizational goals. This creates a lifestyle that revolves around saving and caring for the neglected, unwanted and mistreated animals of society. However, management and the animal shelter employees are at odds on how to best handle the social problem of pet overpopulation. The organization rests upon a traditional hierarchical power distribution where those who perform the stigmatized job task of euthanasia are also those without any real decision-making power. Reducing the animal shelter workers to assembly-line workers in a processing-plant is a key way to ensure the business model of the animal welfare organization flows smoothly. I was employed for a year as an animal attendant in the animal shelter. My ethnographic material includes diary entries, interviews, participant-observations and are represented in my thesis through Crystallization. It is through this unusual form of communication that I use poetry, pictures and narratives to try to engage the reader to understand the unique, emotive context of the organization. In this book, I specifically focus on the paradoxical work role that includes euthanasia of healthy animals; how the hidden voices of the animals give knowledge of the organization; and how power relationships are revealed during emergency evacuation during a natural disaster. The study argues that there are immense problems, both at an organizational as well as broader societal level, of how unwanted animals are dealt with. The focus of powerlessness felt by employees and animals leads to four coping mechanisms throughout the study which I call: Hero, Victim, Professional and Tourist. I make contributions to literatures on Emotion in Organizations, Dirty Work and Positive Organizational Scholarship.
  • Kolu, Anna-Maija (Helsingfors universitet, 2013)
    Spray drying is one way to dry protein medicines and it has many advantages compared to other drying methods, for example it is a fast process. In spray drying high temperature and mechanical stress can inactivate the protein. Disaccharides are generally used as protective agents of protein in spray drying because they have an ability to protect the structure of the protein during drying and storage. Aim of this research was to study the stability of the protein during spray drying and storage by using β-galactosidace as a model protein. Aim was also to characterize the physical properties of trehalose and melibiose and to study how well they protect the protein. Some of the central matters to be examined were the glass transition temperature, crystallinity, water activity, yield of the spray dried powder and protein activity. Especially studying the properties of melibiose in spray drying was important because it has not been used before. The study also included the optimization of the process parameters to be suitable for the product. Trehalose and melibiose transformed to an amorphous form during spray drying. Both XRPD and DSC showed an amorfous form. Trehalose and melibiose proved to be good protective agents for the protein during spray drying and storatge probably because they remained their amorphous structure. β-galactosidase remained activity very well. Optimizing of the process parameters was successful because protein remained its activity and still the powder was quite dry and yield was good. The changes in the structure of the protein were studied with FT-IR but the amount of the protein was too small. Problems caused by the spray drier may have an effect to the results, but on the other hand the spray dryer was made to work optimally.