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Browsing by Subject "kiteyttäminen"

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  • Kiinteäfaasiseulonta itrakonatsoli-malonihappo yhtenäiskiteen kasvattamiseksi 
    Ukkonen, Hanna (2012)
    In medicines APIs are most oftenly at solid form. Crystal forms are more stable than amorphic solid form. Crystals are hold together by intermolecular interactions. Strongest and most common intermolecular interaction in crystals is hydrogen bond. Crystallisation is affected by thermodynamics and kinetics. Same phenomena effect also dissolving of crystals. New APIs often have a poor water solubility which makes them difficult to use. Cocrystals are one way to improve physical characteristics of molecules and most of all solubility. In co-crystals two different solid molecules are crystalliced in a same crystall lattice. Itraconatzole is an API with a poor water solubility. Itraconatzole can form cocrystals with many bicarbocsylicacids. The smallest bicarbocsylicacid that had formed co-crystal with itraconazole is malonic acid. The purpose of the experiment was to grow itraconazole malonic acid co-crystal, which is big enough for single crystall x-ray diffraktion. With SXRD it is possible to find out how molecyles are placed in a crystall lattice. For SXRD the single crystal is not allowed to have a single mistake in its lattice. Itraconazole and malonic acid were dissolved to 1,2-dichloroethane-2-butanone and tetrahydrofurane-chloroform for growing up a single crystal. Crystallisation methods used were evaporation of solvent, adding antisolvent and cooling down of solution. Formed crystalls were analysed with DSC, raman, XRD and TGA. It was succeeded to crystallise itraconazole malonic acid co-crystals with used methods. The formed crystalls were needlelike and packed in small drifts. Any crystall big enough for SXRD was not succeeded to grow up with the methods used. Growing up a bigger co-crystal needs the use of new methods or optimation of the ones used in this experiment.
  • Konditiointiprosessin hallinta ja konditioinnin vaikutus jauhemassan valuvuuteen ja inhalaatioformulaation säilytyksen jälkeiseen pienpartikkeliannokseen 
    Savelainen, Timo (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.

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