Neste trabalho avaliou-se o comportamento coloidal de suspensões nasais contendo micropartículas de celulose (MCC-NaCMC) com o objetivo de desenvolver um produto genérico compatível com o produto referência de mercado. As propriedades reológicas destas formulações possuem alta influência nos atributos críticos de qualidade do produto, como uniformidade de dose, devido sedimentação durante estocagem em prateleira, e também na performance in-vitro/ in-vivo. Realizaram-se testes com diferentes concentrações de MCC-NaCMC e diferentes parâmetros de processo (tempo e taxa de cisalhamento) utilizando um planejamento de experimentos (DoE) de superfície de respostas através de um modelo composto central. As respostas avaliadas foram tamanho de partículas (quantidade em porcentagem de partículas menores que 1µm e D90) através da técnica por difração a laser e viscosidade/tixotropia através de um reômetro rotacional. Influências significativas dos três fatores e efeitos sinérgicos entre eles nas respostas analisadas foram observadas. Desta maneira foi possível obter respostas próximas ao do produto referência de mercado através deste mapeamento. Observou-se também uma alta correlação entre as respostas, pois este estudo mostrou que o tamanho das partículas coloidais controla a viscosidade e tixotropia das dispersões coloidais. Este trabalho mostrou a significativa influência das etapas de processo no comportamento coloidal das formulações. Idealmente o processo deveria ser monitorado por medidas reológicas, porém este controle é inviável devido ao tempo para a reestruturação do sistema (24 horas). Portanto, a melhor alternativa seria o monitoramento do processo por análise de tamanho de partículas online. / In this work, the colloidal behavior of nasal suspensions containing cellulose microparticles (MCC-NaCMC) was evaluated, in order to develop a generic product compatible with the brand-name product. The rheological properties of these formulations have high influence on the critical quality attributes of the product, such as dose uniformity, due to sedimentation during shelf life, and also on in-vitro/in-vivo performance. Tests were performed with different concentrations of MCC-NaCMC and different process parameters (time and shear rate) using a Design of Experiments (DoE) with response surface by central composite design. The responses evaluated were particle size (amount in percentage of particles smaller than 1m and D90) by means of laser diffraction, and viscosity / thixotropy using a rotational rheometer. Significant influences of the three factors and synergic effects among responses were observed. Through this mapping it was possible to obtain nearby responses to the brand-name product. There was also a strong correlation between the responses, because the size of colloidal particles controlled the dispersion viscosity and thixotropy. This study showed the significant influence of the process steps on the colloidal behavior of the formulations. Ideally the process should be monitored by rheological measurements, but this control is not feasible due to the time required for the system rebuilding (24 hours). Therefore, the best alternative would be monitoring the process by the online particle size analysis.

<p>Cellulose powders from various sources were manufactured and characterized to investigate the influence of their crystallinity index, surface area, and pore volume on sorption phenomena and the relevant pharmaceutical functionality. The influence of the cellulose crystallinity index on moisture sorption was important at low and intermediate relative humidities. At high relative humidities, properties such as surface area and pore volume took precedence in governing the moisture sorption process.</p><p>The theory of physical adsorption of gases onto fractal surfaces was useful for understanding the distribution of water in cellulose and the inner nanoscale structure of cellulose particles. It was found that, as a consequence of swelling, moisture induces a fractal nanopore network in cellulose powders that have a low or intermediate degree of crystallinity. On the other hand, no swelling occurs in highly crystalline cellulose powders and moisture sorption is restricted to the walls of the open pores.</p><p>No correlation was found between the cellulose crystallinity index and the incorporation and release of nicotine in cellulose mixtures. By loading nicotine in highly porous matrices of the Cladophora sp. algae cellulose, higher stability against oxidative degradation, higher loading capacity, and more steady release into an air-stream was achieved than when commercially available microcrystalline cellulose was loaded.</p><p>It was also shown that, by manipulating the structure of cellulose, the undesired hydrolysis of acetylsalicylic acid in mixtures with cellulose can be avoided. It was suggested that a broad hysteresis loop between the moisture adsorption and desorption curves of isotherms at low relative humidities could be indicative of an improved compatibility between acetylsalicylic acid and cellulose.</p><p>In all, this thesis demonstrates how the pharmaceutical functionality of microcrystalline cellulose can be improved via engineering of the structure of native cellulose powders.</p>

Cellulose powders from various sources were manufactured and characterized to investigate the influence of their crystallinity index, surface area, and pore volume on sorption phenomena and the relevant pharmaceutical functionality. The influence of the cellulose crystallinity index on moisture sorption was important at low and intermediate relative humidities. At high relative humidities, properties such as surface area and pore volume took precedence in governing the moisture sorption process. The theory of physical adsorption of gases onto fractal surfaces was useful for understanding the distribution of water in cellulose and the inner nanoscale structure of cellulose particles. It was found that, as a consequence of swelling, moisture induces a fractal nanopore network in cellulose powders that have a low or intermediate degree of crystallinity. On the other hand, no swelling occurs in highly crystalline cellulose powders and moisture sorption is restricted to the walls of the open pores. No correlation was found between the cellulose crystallinity index and the incorporation and release of nicotine in cellulose mixtures. By loading nicotine in highly porous matrices of the Cladophora sp. algae cellulose, higher stability against oxidative degradation, higher loading capacity, and more steady release into an air-stream was achieved than when commercially available microcrystalline cellulose was loaded. It was also shown that, by manipulating the structure of cellulose, the undesired hydrolysis of acetylsalicylic acid in mixtures with cellulose can be avoided. It was suggested that a broad hysteresis loop between the moisture adsorption and desorption curves of isotherms at low relative humidities could be indicative of an improved compatibility between acetylsalicylic acid and cellulose. In all, this thesis demonstrates how the pharmaceutical functionality of microcrystalline cellulose can be improved via engineering of the structure of native cellulose powders.

Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

In the pharmaceutical industry, it is always important to have reproducible processes and raw materials of high quality to ensure good quality products. AstraZeneca, that is a leading manufacturer of different pharmaceuticals, works according to GMP to make sure that their processes deliver products of the same quality every time. A problem that has occurred at AstraZeneca is when a raw material is not properly understood and variations in the raw material affects the final product. Variations in drug release in one of AstraZeneca´s products, Product X, has been linked to the cushioning excipient Microcrystalline cellulose (MCC). Variations in drug release has been noticed during change from one batch of MCC to another. The aim of this study was to investigate which material attributes of MCC that contributes to variations in the final product. Particle size and moisture content were identified as critical material attributes (CMA´s) and were therefore chosen to be investigated more thoroughly. By variating particle size and moisture content during manufacturing of Product X, the influence of these attributes could be investigated using Design of Experiment (DoE). An additional experiment that compared two MCC batches from different suppliers was also performed during this study. The results from these experiments showed that the particle size and moisture content of MCC does affect the drug release. Large particles and high moisture content gave rise to a faster drug release compared to small particles and low moisture content that gave rise to a slower drug release. It is however hard to draw conclusions regarding how small differences in particle size and moisture content could affect the drug release.

[pt] A busca por materiais que não impactem negativamente o meio ambiente tem sido uma das prioridades de engenheiros que trabalham com materiais de construção. A emissão expressiva de CO2 na produção de cimento contribui para tal preocupação. Dentro deste cenário, soluções com emprego de nanotecnologia vêm chamando a atenção em diversas áreas por proporcionar novas soluções. O principal objetivo da presente tese é associar um material proveniente de uma fonte natural com benefícios provenientes da nanotecnologia a fim de modificar propriedades de pastas de cimento considerando seus aspectos químicos, físicos e mecânicos. A nanocelulose se apresenta como material proveniente de fonte renovável que apresenta propriedades atraentes aos materiais cimentícios, sendo assim uma opção a ser utilizada em conjunto com o cimento. Dentre os diversos tipos disponíveis, a celulose nanofibrilada (CNF) foi elencada para ser investigada neste trabalho. A celulose microcristalina (CMM) foi incluída nas investigações para possibilitar uma comparação direta entre as fibrilas da CNF e as partículas de CMM. O uso desses materiais celulósicos pode ser considerado recente e, com isso, existem ainda lacunas no que tange o entendimento dos seus efeitos em materiais cimentícios. Assim, a viabilidade da CNF e da CMM enquanto reforços em pastas de cimento foi avaliada por meio de ensaios de compressão e flexão. Os possíveis mecanismos responsáveis pelo efeito de ambas CMM e CNF foram estudados por meio de análises químicas e físicas. Por fim, foi realizada a caracterização das pastas reforçadas quanto à retração, total e autógena, e à reologia, nos regimes estático e dinâmico. Por conta dos impactos na trabalhabilidade promovidos pela inclusão de CNF, a mistura delas nas pastas de cimento foi facilitada com a adição de superplastificante, especialmente em porcentagens maiores que 0.050 por cento, em peso. A CMM e a CNF se mostraram eficazes em reforçar as pastas de cimento quanto a esforços de flexão e tração, levando ao aumento das respectivas resistências e módulos. Os resultados obtidos mostraram que a água presente no gel da CNF não está totalmente disponível como água de mistura por conta da morfologia e hidroficilidade das fibrilas. Observada uma certa combinação de porcentagem e fator água-cimento, a inclusão de CNF diminuiu a retração autógena das pastas. A inclusão de 0,040 por cento de NFC levou a resultados semelhantes aos da adição de CMM referente ao aumento da tensão de escoamento e da viscosidade. / [en] The seek for low environmental impact materials has become one of the priorities of construction building materials engineers. One of the reasons is the massive growing contribution of cement production industry in worldwide CO2 emissions. In this scenario, the dissemination of nanotechnology into varied areas is drawing attention for enabling new possibilities. The idea of the present thesis is to associate a material provided from a natural source with the potential benefits of nanotechnology to modify conventional cement pastes regarding their chemical, physical and mechanical aspects. Nanocellulose arises as an alternative that meets an eco-friendly source with remarkably properties expected from nanomaterials. There are different types of nano cellulosic materials that may be tailored to achieve desired compatibilities with varied cementitious materials. In this work, nanofibrillated cellulose (NFC) in the form of gel, and microcrystalline cellulose (MCC) particles were investigated, so a comparison could be traced between them. The use of both NFC and MCC in cementitious materials is recent and there are important gaps regarding their effect. For that reason, the feasibility of MCC and NFC to act as reinforcement on cement pastes was evaluated through compressive and flexural tests. Then, the possible mechanisms behind the effect of MCC and NFC on the microstructure of cement pastes were investigated through distinct chemical and physical analyses. Moreover, the total and autogenous shrinkage were characterized, as well as the dynamic and static rheological behaviors. Due to rheological modifications, the mixture of cement pastes with NFC was facilitated by a superplasticizer, especially for percentages higher than 0.050 percent wt. The MCC and NFC promoted the reinforcement of the cement pastes, regarding flexural and tensile stresses, increasing the composite strength and modulus. It was observed that he water present in the NFC gel is not totally available as mixing water due to the morphology and hydrophilicity of the fibrils. If associating certain levels of inclusions and water ratio, the NFC inclusion led to a decrease in autogenous shrinkage. The addition of 0.040 percent of NFC resulted in similar outcomes to 1.000 percent of MCC regarding their ability to increase yield stress and viscosity.

<p>Relationships between stresses during the drying process, particle structural and functional properties, and particle engineering by the drying process were addressed in this thesis. In the first part, the importance of the drying phase and the effect of the drying rate on the intragranular porosity of microcrystalline cellulose pellets were investigated. Differences in porosities of dried pellets could be explained by liquid-related differences in densification during convective drying rather than by differences in densification during wet agglomeration. An increased drying rate gave more porous pellets with a lower compression shear strength, and thereby stronger tablets. The next part dealt with modulation of solid-state stability and tabletting behaviour of amorphous lactose by incorporation of different polymers by spray drying. Increased content and molecular weight of poly(vinylpyrrolidone) (PVP) resulted in an increased resistance to crystallisation provoked by heat and moisture. The stabilising effect was even more evident after long-term storage. However, the glass transition temperature was almost unaffected and may, therefore, be questioned as a stability indicator for these types of materials. The presence of the polymers resulted in somewhat less deformable particles. Incorporation of PVP increased the compactability, whilst a surfactant decreased it, which could be shown to be related to differences in particle-particle adhesivity between the different particles. This thesis contributes to increased mechanistic understanding in the area of particle engineering that may lead to better prediction and optimisation of the functionality of pharmaceutical particles, which is of the utmost importance in the development and production of solid dosage forms.</p>

Relationships between stresses during the drying process, particle structural and functional properties, and particle engineering by the drying process were addressed in this thesis. In the first part, the importance of the drying phase and the effect of the drying rate on the intragranular porosity of microcrystalline cellulose pellets were investigated. Differences in porosities of dried pellets could be explained by liquid-related differences in densification during convective drying rather than by differences in densification during wet agglomeration. An increased drying rate gave more porous pellets with a lower compression shear strength, and thereby stronger tablets. The next part dealt with modulation of solid-state stability and tabletting behaviour of amorphous lactose by incorporation of different polymers by spray drying. Increased content and molecular weight of poly(vinylpyrrolidone) (PVP) resulted in an increased resistance to crystallisation provoked by heat and moisture. The stabilising effect was even more evident after long-term storage. However, the glass transition temperature was almost unaffected and may, therefore, be questioned as a stability indicator for these types of materials. The presence of the polymers resulted in somewhat less deformable particles. Incorporation of PVP increased the compactability, whilst a surfactant decreased it, which could be shown to be related to differences in particle-particle adhesivity between the different particles. This thesis contributes to increased mechanistic understanding in the area of particle engineering that may lead to better prediction and optimisation of the functionality of pharmaceutical particles, which is of the utmost importance in the development and production of solid dosage forms.