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Os fármacos pertencentes às classes II e IV do sistema de classificação biofarmacêutica são aqueles sujeitos a problemas relacionados com a sua biodisponibilidade. Um dos procedimentos utilizados para melhorar a solubilidade de fármacos pouco solúveis é a granulação com materiais lipídicos ou cerosos. Para aumentar a solubilidade da carbamazepina, fármaco de classe II, ou seja, que apresenta baixa solubilidade e alta permeabilidade, inicialmente esta foi associada com os excipientes Gelucire® 50/13 ou Polietilenoglicol 6000, através de uma mistura física ou dispersão sólida. Estas associações foram submetidas a procedimentos analíticos como DSC, Infravermelho, Difração de Raios-X e teste de solubilidade em água. Nas misturas físicas a carbamazepina permaneceu estável, porém nas dispersões sólidas houve o aparecimento de polimorfismo. No entanto estes polimorfos também apresentam atividade terapêutica. As misturas físicas e as dispersões sólidas foram submetidas ao teste de solubilidade e as amostras que continham Gelucire® 50/13 aumentaram em torno de 15 vezes a solubilidade da carbamazepina em água, enquanto que as amostras que continham Polietilenoglicol 6000 aumentaram em torno de 14 vezes. Optou-se pela utilização do PEG 6000 devido à melhor compatibilidade deste com o equipamento utilizado. A granulação por Hot Melt em leito fluidizado foi realizada após alguns ensaios de fluidodinâmica utilizando a lactose spray dried como substrato. Durante os experimentos as condições do processo permaneceram estáveis e a curva característica foi típica de leito fluidizado. Os granulados foram obtidos utilizando o planejamento fatorial Box Behnken cujos fatores estudados foram: vazão de dispersão sólida, quantidade de dispersão sólida e pressão de atomização e em seguida caracterizados e avaliados. A maioria das propriedades físicas e farmacotécnicas dos granulados foi dependente da quantidade de dispersão sólida. A utilização do método de granulação por fusão em leito fluidizado melhorou o perfil de dissolução das cápsulas contendo os granulados, sendo que com o maior nível da quantidade de dispersão sólida houve um aumento significante na quantidade de carbamazepina liberada. Os resultados mostram que esta técnica é relevante para preparar dispersões sólidas com fármacos que apresentam baixa biodisponibilidade devido a sua baixa solubilidade. / Drugs belonging to classes II and IV in the biopharmaceutical classification system are those having bioavailability problems. Granulation with waxy lipids is one of the procedures used to improve the solubility of poorly soluble drugs. To increase the solubility of carbamazepine a drug of class II that has low solubility but high permeability, its association with the excipients Gelucire® 50/13 or Polyethylene 6000, was done by physical mixtures or solid dispersions. The associations were subjected to analytical procedures such as Differential Scanning Calorimetry (DSC), infrared light, X-ray diffraction and tests of solubility in water. In physical mixtures carbamazepine remained stable, but showed different polymorphic forms in solid dispersions. However, the polymorphic forms were also therapeutically active.Solubility tests of physical mixtures and solid dispersions indicated that samples containing Gelucire ® 50 / 13 increased the solubility of carbamazepine in water about 15 times, while the ones containing Polyethylene glycol 6000 had an increase of about 14 times. PEG 6000 was the chosen carrier due to its better compatibility with the equipment used.Fluid dynamic tests using spray dried lactose as a substrate were preliminary to the granulation experiments in the fluidised bed. The process conditions remained stable during the experiments and the characteristic curve tracing was typical of fluidised beds. Granules were obtained in experiments that followed a Box Behnken factorial design, where the factors studied were: flow rate of the solid dispersion, amount of solid dispersion and atomization pressure .Most physical and technical granule properties were dependent on the quantity of solid dispersion. The method of granulation by hot melt in a fluidised bed improved the solubility profile of carbamazepine in granule containing capsules.Granules containing the highest amount of solid dispersion showed a significant increase in the amount of carbamazepine released. The results proved that this technique is relevant to the preparation of solid dispersions with low bioavailable drugs due to their poor solubility.

A granulação através do uso de dispersões sólidas é um recurso que pode ser utilizado para aumentar a solubilidade de fármacos pouco solúveis, como no processo de Hot Melt Granulation (HMG). Este processo pode ser realizado utilizando-se o aparelho de leito fluidizado, com a atomização de uma dispersão fundida de carreadores solúveis com fármacos pouco solúveis sobre um substrato efetuando sua granulação. Essa é uma alternativa em relação aos métodos de granulação tradicionais, sendo vantajoso por não utilizar solvente. O objetivo deste trabalho foi realizar a granulação de piroxicam por HMG em leito fluidizado com polietilenoglicol (PEG) na forma de dispersão fundida, usando lactose spray dried como substrato com o intuito de aumentar a solubilidade do fármaco que é pouco solúvel em água, classificado como classe 2 (baixa solubilidade e alta permeabilidade) no Sistema de Classificação Biofarmacêutica. Foi realizada também a avaliação de misturas físicas e dispersões sólidas dos excipientes e do fármaco para obter informações de pré-formulação. O processo de granulação em leito fluidizado foi realizado através de um planejamento fatorial do tipo Box-Behnken, no qual as variáveis de operação carga de substrato, vazão do ar do bico de atomização e altura do bico de atomização foram variadas para a caracterização do processo e o estudo do efeito das variáveis do processo sobre as propriedades dos grânulos também foi realizado. Os grânulos obtidos foram caracterizados pela avaliação das propriedades farmacotécnicas, doseamento, distribuição granulométrica e também pela determinação das propriedades físico-químicas através de análises de calorimetria exploratória diferencial (DSC), espectroscopia no infravermelho e difração de raios-X. O perfil de dissolução de cápsulas contendo os grânulos também foi determinado. De acordo com as análises realizadas, não ocorreram interações nas misturas físicas e dispersões sólidas, nem nos granulados obtidos. Em relação aos grânulos, o resultado da avaliação farmacotécnica demonstrou que a maioria apresentou valores de fluxo excelente e bom. Através da distribuição granulométrica e das imagens dos grânulos obtidas por microscopia eletrônica de varredura (M.E.V.), pode-se observar que ocorreu a aglomeração das partículas de lactose pela atomização da dispersão de piroxicam e PEG 4000. Na avaliação do perfil de dissolução, os grânulos mostraram-se com uma solubilidade superior ao piroxicam isolado, sendo a granulação por Hot Melt em leito fluidizado um processo vantajoso em relação aos métodos atuais de granulação. / Granulation through solid dispersions may be employed to increase drug solubility as in the Hot Melt Granulation (HMG). Fluidized beds are used in the procedure, which by atomizing a melted dispersion of soluble carriers and low solubility drugs on a substrate produces the desired granulation. This is an advantageous alternative to traditional granulation methods since solvents are not involved. The objective of this study was to granulate the low solubility drug, piroxicam, by HMG in a fluidized bed with polyethylene glycol (PEG) in the form of a melted dispersion and dried lactose spray as the substrate. The drug has low aqueous solubility and is classified as Class 2 (low solubility and high intestinal permeability) in the Biopharmaceutical Classification System (BCS). Physical mixtures and solid dispersions of excipients and drug were previously tested as to obtain pre-formulation data. A factorial planning of the Box-Behnken type was used for the granulation in a fluidized bed, with the operation variables as substrate load, air stream velocity through the atomizing outlet and its height being varied to characterize the process and to verify their effects on the granule properties. Characterization of the granules was by evaluation of pharmacotechnical properties, dosage of active principle, granule size distribution and also by physicochemical analyses. These were by differential scanning calorimetry (DSC), infrared spectroscopy and X-ray diffraction. Interactions in the physical mixtures, solid dispersions and granules were not detected. The dissolution profile of capsules containing the granules was determined. Evaluation results showed that most granules had excellent to good flux properties. Granulometric distribution and scanning electron microscopy (SEM) images indicated agglomeration of lactose particles by the atomization of the piroxicamPEG dispersion. Evaluating the granule dissolution profiles it was shown that they were more soluble than piroxicam only. These results suggest that granulation by Hot Melt in a fluidized bed is process with advantages when compared to methods currently used.

Fármacos pouco solúveis em água tendem a possuir baixa biodisponibilidade. Diversos métodos têm sido estudados para promover o aumento da solubilidade em água de fármacos pouco solúveis. As dispersões sólidas têm sido pesquisadas como uma estratégia de aumentar a solubilidade em água e melhorar o desempenho destes fármacos na biodisponibilidade, entretanto os mecanismos completamente elucidados parecem variar da combinação do fármaco e do polímero, bem como do método de obtenção empregado. No presente estudo, através da técnica de evaporação do solvente desenvolveu-se dispersões sólidas de loratadina em polivinilpirrolidona a fim de melhorar a solubilidade do fármaco. / Poorly water soluble drugs tend to have low bioavailability. Several methods have been studied to promote increased water solubility of poorly soluble drugs. Solid dispersions have been investigated as a strategy to increase the water solubility and improve performance on the bioavailability of these drugs, however elucidated the mechanisms seem to vary the combination of drug and polymer and production method employed. In this study, using the technique of solvent evaporation was developed from solid dispersions in polyvinylpyrrolidone loratadine to improve the solubility of the drug.

A doença de Chagas representa um grave problema de saúde pública, afetando principalmente a população de baixa renda, o que a torna negligenciada pela indústria farmacêutica. Atualmente, existe apenas um fármaco disponível para o tratamento, o benzonidazol, porém este apresenta eficácia limitada e está associado a diversos efeitos colaterais. O ácido ursólico, um triterpeno de origem natural, possui atividade tripanocida, porém, sua solubilidade aquosa baixa limita sua biodisponibilidade. Para o aumento da biodisponibilidade tem destaque o uso das dispersões sólidas, onde fármacos lipofílicos são dispersos molecularmente ou no estado amorfo em carreadores hidrofílicos, acarretando um aumento do perfil de dissolução. Neste trabalho, dispersões sólidas e misturas físicas contendo ácido ursólico foram preparadas com os carreadores polietilenoglicol 6000, Gelucire 50/13 e dióxido de silício coloidal, Poloxamer 407 e caprato de sódio, empregando as técnicas de fusão e evaporação do solvente. Os sistemas foram caracterizados através das técnicas de microscopia eletrônica de varredura, espectroscopia do infravermelho com transformada de Fourier, calorimetria exploratória diferencial, microscopia em hot stage e difratometria de raios-X. Em outra etapa, os produtos foram avaliados quanto à solubilidade aquosa, perfil de dissolução in vitro, citotoxicidade em linhagem celular LLC-MK2, e atividade tripanocida em modelo animal. Em conjunto, os resultados mostraram que o fármaco não teve suas propriedades afetadas pela manipulação em misturas físicas, mantendo sua estrutura cristalina. Por outro lado, os experimentos de difratometria de raios-X e as observações microscópicas em hot stage revelaram a alteração do ácido ursólico para o estado amorfo, principalmente para os sistemas preparados pelo método do solvente, enquanto que algumas formulações manipuladas pelo método da fusão exibiram alterações polimórficas. Além disso, evidenciaram-se interações intermoleculares do tipo ligações de hidrogênio para as dispersões sólidas preparadas pelo método do solvente. As alterações do fármaco observadas para as dispersões sólidas preparadas pelo método do solvente aumentaram sua solubilidade e melhoraram seu perfil de dissolução comparado às dispersões sólidas pelo método da fusão e misturas físicas, sendo este aumento maior para os sistemas compostos por Poloxamer 407 + caprato de sódio, seguido por Poloxamer 407, Gelucire 50/13 + dióxido de silício coloidal e PEG 6000, o que pode ser atribuído ao poder tensoativo dos três primeiros carreadores. As formulações mostram-se seguras até a concentração de 128 ?M do fármaco, através da avaliação da citotoxicidade. Por último, o ursólico teve um aumento significativo da atividade tripanocida para a formulação composta pelo tensoativo Poloxamer 407 junto com o promotor de absorção oral caprato de sódio, manipulada pelo método do solvente, sugerindo o aumento da biodisponibilidade do fármaco. / Chagas disease represents a severe problem in public health, affecting mainly the low-income population, making it neglected by the pharmaceutical industry. Currently, there is only one drug available for treatment, benznidazol, however, it presents limited efficacy and is associated with several side effects. Ursolic acid, a naturally occurring triterpene, presents trypanocidal activity, but its low water solubility limits the bioavailability. To increase the biovailability, solid dispersions, where lipophilic drugs are molecularly or in the amorphous state dispersed in hydrophilic carriers, can play an important role, resulting in enhanced dissolution profile of the drug. In this work, solid dispersions and physical mixtures containing ursolic acid were prepared with Polyethyleneglycol 6000, Gelucire 50/13 and silicon dioxide, Poloxamer 407 and sodium caprate as carriers, employing the fusion and solvent evaporation techniques. The products were characterized through scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, hot stage microscopy and X-ray diffractometry. In another step, the formulations were evaluated regarding the aqueous solubility, in vitro dissolution profile, citotoxicity using LLC-MK2 cell line, and trypanocidal activity in animal model. Together, results showed that the drug did not suffer any change in its properties when in physical mixture. On the other hand, X-ray diffractometry and hot stage microscopy revealed a transition from the crystalline to the amorphous state for ursolic acid, especially for the products prepared by the solvent method. In the fusion method, some formulations exhibited a polymorphic change. Moreover, we identified intermolecular interactions between drug and carrier by hydrogen bonding in the products prepared by the solvent method. These changes observed for solid dispersions prepared by the solvent method resulted in increased water solubility and dissolution profile and these effects were higher for the products prepared with Poloxamer 407 + sodium caprate, followed by Polomer 407 alone, Gelucire 50/13 + silicon dioxide and PEG 6000, which can be attributed to the surfactant property of the three first carriers. The formulations were safe up to 128 ?M of the drug, showed by the citotoxicity evaluation. Very importantly, we highlight that ursolic acid had a significant increase in the trypanocidal activity for the product prepared with the surfactant Poloxamer 407 and the penetration enhancer sodium caprate, prepared by the solvent method, suggesting that in this composition ursolic acid was more bioavailable.

<p>The symmetry requirements of both second harmonic generation (SHG) and triboluminescence (TL) provide outstanding selectivity to noncentrosymmetric crystals, leading to high signal to noise measurements of crystal growth and nucleation of active pharmaceutical ingredients (API) within amorphous solid dispersions (ASD) during accelerated stability testing. ASD formulations are becoming increasingly popular in the pharmaceutical industry due to their ability to address challenges associated with APIs that suffer from poor dissolution kinetics and low bioavailability as a result of low aqueous solubility. ASDs kinetically trap APIs into an amorphous state by dispersing the API molecules within a polymer matrix. The amorphous state of the API leads to an increase in apparent solubility, faster dissolution kinetics, and an increase in bioavailability. Both SHG and TL are used to quantitatively and qualitatively detect the crystal growth and nucleation within ASD formulations at the parts per million (ppm) regime. TL is the emission of light upon mechanical disruption of a piezoelectrically active crystal. Instrumentation was developed to rapidly determine the qualitative presence of crystals within nominally amorphous pharmaceutical materials in both powders and slurries. SHG was coupled with a controlled environment for <i>in situ</i> stability testing (CEiST) to enable <i>in situ</i> accelerated stability testing of ASDs. Single particle tracking enabled by the CEiST measurements provided insights into crystal growth rate distributions present due to local differences within the material. Accelerated stability testing monitored by <i>in situ</i> measurements increased the signal to noise in recovered nucleation and crystal growth rates by suppressing the Poisson noise normally present within conventional accelerated stability tests. The disparities between crystal growth and nucleation kinetics on the surface versus within bulk material were also investigated by single particle tracking and <i>in situ </i>measurements. Crystals were found to grow faster in the bulk compared to single crystals growing on the surface while total crystallinity was found to be higher on the surface due to radial growth habits of crystals on the surface compared to columnar growth within the bulk. To increase the throughput of the <i>in situ </i>measurements, a temperature and relative humidity array (TRHA) was developed. The TRHA utilizes a temperature gradient and many individual liquid wells to enable the use of a multitude of different conditions at the same time which can reduce time required to inform formulations design of stability information. </p>

CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical technology Name and surname: Marie Korpasová Title of diploma thesis: Adhesive and rheological properties of mixtures based on chitosan Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Diploma thesis deals with evaluation of rheological and adhesive properties of compounds for matrix tablets formulation, based on Chitosan with addition of retardant compound. The retardant compound consists of Sodium Alginate and Hypromellose in concentrations of 30 %, 40 % and 50 %. Theoretical part describes Chitosan, Sodium Alginate and Hypromellose. As next is division of matrix tablets. Theoretically is also described evaluation of rotational, oscillational and adhesive testing which was used in practical part. From viscosity curves can be seen, that viscosity is decreasing with increasing stress. Viscosity increases with increasing concentration of Sodium Alginate and Hypromellose. Oscillational testing is better for gel characterization, because it provides lower stress on test samples. Samples of given compound were prepared by hydrating with phosphate buffer of pH 6,8. Coefficient of consistency K and index flow rate n characterize rheological behaviour of gels. Viscoelastic compounds behave like solids with plastic...

The success of an amorphous solid dispersion (ASD) formulation, consisting of a homogeneous molecular dispersion of drug and polymer, relies on its ability to create and maintain a supersaturated solution. However, supersaturated solutions are metastable and prone to crystallization. In solution, crystals are expected to serve as a template for crystal growth, depleting achieved supersaturation. Thus, in an ASD product, ideally no crystallinity should be present. However, technical challenges exist in both processing and characterization to routinely ensure this is achieved. The presented studies follow the process design, characterization, and dissolution performance of hot melt extruded amorphous solid dispersions, seeking insight into the significance of critical quality attributes of resulting extrudates, namely residual crystallinity and thermal degradation.<div>Selection of hot melt extrusion (HME) processing conditions to prepare ASDs is governed by thermodynamic and kinetic attributes of the drug and polymer system. Mapping the temperature-composition phase diagram to HME processing conditions provides a processing design strategy to prevent residual crystallinity while simultaneously avoiding thermal degradation. Through processing temperatures below the drug’s melting point (Tm) and above the formulation critical temperature (Tc), fully amorphous systems could be generated if sufficient kinetics were provided. The utility of thermogravimetric analysis was critically examined for prediction of the chemical stability processing window for HME formulations.<br></div><div>For characterization and product performance characterization, residual crystalline content in HME ASDs can be anticipated and tailored to various levels. Several HME ASDs were characterized by a range of analytical techniques, highlighting the sensitivity of available techniques to qualitatively or quantitatively detect crystalline content (depending on limitations which stem from properties of the instrument or sample). Transmission electron microscopy (TEM) was found to identify low levels of crystallinity not observed by other technique and provide insight into crystal dissolution mechanisms. A defect-site driven dissolution and fragmentation model was suggested, and supported by a Monte Carlo simulation, underscoring that crystal defect sites, either intrinsic to the crystals or formed during processing, expedite dissolution rates and generation of new surfaces for dissolution.<br></div><div>Non-sink dissolution was performed for indomethacin/PVPVA HME ASD samples with residual crystallinity ranging from 0-25% crystalline content. Due to effective crystal growth inhibition by the polymer, crystals had little impact on dissolution performance. Achieved supersaturation was reduced approximately by the level of crystallinity present, i.e. a lost solubility advantage. These studies have significance for HME processing design and risk assessment of crystallinity within ASD formulations.<br></div>

CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Name of author: Dominik Vavřich Title of diploma thesis: Rheological behaviour of mixtures for freeze-drying Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The diploma thesis deals with the evaluation of rheological properties of aqueous dispersions of fish gelatin and carrageenans intended for lyophilization. Theoretical part of this work is dedicated to the characterization of fish gelatin and carrageenans which were used for preparation of the mixtures in experimental part of this work. Characterization of an oral cavity from an application of medicaments point of view and an orally disintegrating tablets of the medicine with a focus on the lyophilized tablets are also presented. Mixtures of the fish gelatin and the carrageenans were prepared in the experimental part of the work. Their rheological behaviour employing an absolute rotational rheometer Kinexus Pro+ was measured and evaluated. Also, the testing of the rheological characteristics of these materials transformed into the freeze-dried tablets was performed. Nonlinear viscous curves were obtained, and they were mathematically evaluated by the Power law model. Pseudoplastic behaviour of the mixtures can be derived from the results of acquired...

Using various synthetic strategies, we designed several libraries of novel polysaccharide mixed ester derivatives for oral drug delivery applications. Cellulose and cellulose esters have been extensively studied and utilized for different applications such as separation membranes, sustainable plastics, and enteric coatings in oral drug delivery carriers. We sought to exploit the ring-opening of cyclic anhydrides, succinic and glutaric anhydride, to append ω-carboxyl groups to commercially available cellulose and cellulose ester substrates. We used scalable synthetic strategies and widely available and cheap reagents to show a proof-of-concept for the manufacturability of these different polymer derivatives. We incorporated different degrees of substitution of ω-carboxyl groups to impart a range of water solubility in these polymers. The derivatives displayed excellent <i>T</i>g values for ASD applications, adequate water solubility, and good amphiphilic properties. We designed very effective amorphous solid dispersion (ASD) oral drug delivery polymers that prevented recrystallization of felodipine for hours and had excellent congruent polymer-drug release from the formulation at 20% drug loading. During the ring-opening reactions of the cellulose derivatives with glutaric anhydride we discovered that crosslinking and gelation can occur, especially with cellulose and cellulose ester substrates with a high degree of substitution (DS) of hydroxy groups. We isolated and characterized these gelled products using rheology, and solid-state 1D and 2D NMR spectroscopy, to evaluate whether the gels are physical or chemical in nature and proposed a mechanism for gelation. We determined that the gels are mostly physical but can proceed to chemical crosslinking over time. We designed a library of cellulose ester derivatives, and we investigated their performance as amorphous solid dispersion (ASD) drug delivery vehicles for the lipophilic drug felodipine, through <i>in vitro</i> experiments. Aside from felodipine, many other active pharmaceutical ingredients (APIs) are also highly crystalline and poorly water-soluble. ASDs are used to disrupt the crystalline packing of these drugs through dispersing them in amorphous polymeric carriers, facilitating their water-solubility, and preventing their recrystallization. We showed that our polymers performed remarkably well in the <i>in vitro</i> studies and inhibited crystallization of model compound felodipine for several hours while providing optimal drug release, affording highly promising ASD polymers. If company formulators are unable to develop an effective oral-delivery carrier to prevent a drug from recrystallizing, then the drug cannot be tested in <i>in vivo</i> toxicology studies, and therefore cannot be brought to market because of its poor aqueous solubility and subsequent low bioavailability. To test the robustness of our polymers, we also performed <i>in vitro</i> ASD experiments at the pharmaceutical company AbbVie with their most rapidly crystallizing pipeline compounds, and several commercially available drugs (Compound A, axitinib, and ziprasidone). We demonstrated that our polymers could also prevent drug recrystallization with these rapid crystallizers, outperforming commercial polymers like FDA-approved hydroxypropyl methyl cellulose acetate succinate (HPMCAS (MF)), even at exceptionally high drug loading ratios of 40 times the concentration of polymer. α-1,3-Glucans are an emerging class of polysaccharides and are structurally different than cellulose due to their α (1→3) linkage versus the cellulose β (1→4) glycosidic linkage. We demonstrated that we could modify these derivatives using a variety of esterification strategies and TEMPO-mediated C6 selective oxidation, affording a myriad of different novel polymer products, some of which are structural analogs of the cellulose ester derivatives we previously created. The polymers had higher <i>T</i>g values than the cellulose ester polymers, which may be useful for applications where heat resistance is desired. In the future, we will screen some of these α-1,3-glucan derivatives with poorly water-soluble enzalutamide, posaconazole and celecoxib model drugs, to evaluate their crystallization inhibition properties and the influence of polymer morphology upon structure-property relationships. We expect that these synthetic polymer strategies will offer scalable routes to novel ASD polymers, which we demonstrated to be highly effective drug crystallization inhibitors against a variety of different hydrophobic pharmaceutical compounds. / Doctor of Philosophy / Polysaccharides are polymers comprised of many linked sugar molecules and are an incredibly abundant and renewable resource. They are found everywhere in nature such as the wood from trees, the shells of crabs, the exoskeletons of bugs, and the mushrooms that sprout in damp forests. The research in this dissertation focuses on the use and chemical modification of polysaccharides for designing new, polysaccharide-based oral drug delivery systems called amorphous solid dispersions (ASDs), which significantly aid in the solubility and bioavailability of important medications. We started with the chemical modification of cellulose, the most abundant plant polysaccharide on planet Earth, and previously modified commercial cellulose substrates (known as cellulose esters) to create novel polymers for ASDs. We successfully modified these polymers, characterized them, and evaluated their potential as oral drug delivery vehicles by formulating them with several different classes of potent drugs used to treat a variety of diseases such as hypertension and schizophrenia. We showed that our designed cellulose ester polymers kept these hydrophobic drugs water-soluble for long-enough so that they can be adequately absorbed in the human body through the gastrointestinal tract, significantly outperforming commercial polymers in many cases. During the chemical modification of the cellulose esters, we also observed that they were prone to form gels, and we investigated this gelation phenomena in more detail through rheometry, 1D and 2D solid-state nuclear magnetic resonance spectroscopy (similar in principle to the medical diagnostic method, magnetic resonance imaging or MRI). We discovered that these gels can be physically and/or chemically linked together, and that different gelation mechanisms can dominate depending on the polysaccharide substrate and the esterification reagent used. We extended our research to other polysaccharide derivatives called α-1,3-glucans, which can be sourced from fungi, and/or enzymatically synthesized in the lab. Using various synthetic esterification and oxidation chemical methods to functionalize this polysaccharide, we designed a library of entirely novel polymers with different physical structures relative to the cellulose ester polymers. The polymers displayed thermal properties that show promise in drug delivery vehicle applications and in applications where high heat resistance is required. Overall, we developed next-generation polymers for amorphous solid dispersion oral drug delivery applications. We displayed the versatility of using a select few chemistry strategies to create a variety of different polymers with very different physicochemical properties. We hope that this work will help researchers design sustainable, plant-based polymers for ASD applications and we hope to nurture future structure-function studies to improve ASD performance for the benefit of patients in need.