A hidrofobicidade e a estrutura planar do orbital π estendido de fotossensibilizadores do tipo clorina e hipericina podem favorecer a agregação destes compostos em meio aquoso. Esta agregação pode reduzir a eficiência fotodinâmica e a aplicabilidade destes compostos em diagnósticos e na Terapia fotodinâmica. Uma estratégia para minimizar esta limitação é a modificação destas moléculas pela inserção de grupos hidrofílicos. Neste trabalho foram utilizadas técnicas espectroscópicas para caracterizar as propriedades físico-químicas e fotodinâmicas de derivados de clorina (CHL), e hipericina (HY) obtidos por meio de inserções dos grupos hidrofílicos trizma e glucamina, respectivamente: Clorina-Trizma (CHL-T) e Hipericina Glucamina (HY-G). Os resultados mostraram que estas modificações estruturais aumentaram em até 20% a solubilidade destes compostos em meio aquoso. No entanto, devido à solubilidade parcial dos fotossensibilizadores na ausência de cargas elétricas foram identificados agregados do tipo H em meio ácido, neutro e na presença de íons em solução aquosa. Tais agregados foram solubilizados em meio alcalino e por microambientes micelares dos surfactantes CTAB, SDS e Tween 20. Os agregados do tipo H acarretaram ainda na redução da constante de velocidade de fotobranqueamento e da formação de oxigênio singleto dos fotossensibilizadores em meio aquoso. Contudo, as clorinas foram cerca de 15 vezes mais eficientes do que a hipericinas na geração deste radical citotóxico. A análise sistemática do potencial fotodinâmico dos fotossensibilizadores em células VERO e HUVEC (não tumorais) e HEp-2 (tumoral) foi realizada por meio de um planejamento fatorial combinando-se a concentração, tempo de acumulação do fotossensibilizador no interior da célula e a dose de luz. Esta análise mostrou que o tempo de acumulação do fotossensibilizador é um parâmetro significante para se erradicar seletivamente as células cancerígenas. Ao contrário das células não tumorais, nas células HEp-2 a quantidade de fotossensibilizador acumulado foi proporcional à lipoficilidade dos fotossensibilizadores. A análise quimiométrica resultou ainda em um modelo matemático para a estimativa dos valores da concentração inibitória média que foi validada por meio de comparação estatística com os valores experimentais determinados para os fotossensibilizadores. As hipericinas foram mais fototóxicas para as células tumorais do que as clorinas. Nas células não tumorais os derivados foram menos citotóxicos, sugerindo o uso destes compostos para a inativação seletiva de células tumorais. Todas essas características permitem que os compostos sejam empregados como fotossensibilizadores em diagnósticos e tratamentos fotodinâmicos. / The hydrophobicity and planar structure of π extended orbital of photosensitizers like chlorine and hypericin may favor the aggregation of these compounds in aqueous medium. This aggregation can reduce their photodynamic efficiency and applicability in Photodynamic Therapy and diagnosis. A strategy to minimize this limitation is the modification of these molecules by the inclusion of hydrophilic groups. In this study spectroscopic techniques were used to characterize the physical-chemistry and photodynamic properties of chlorin (CHL) and hypericin (HY) derivatives obtained by insertion of trizma glucamine and hydrophilic groups, respectively: Trizma-Chlorin (CHL-T) and glucamine Hypericin (HY-G). The results showed that these structural modifications increased by 20% the solubility of these compounds in an aqueous medium. However, due to partial solubility of the photosensitizers in electric charges absence, H-aggregates were found in acid, neutral and ions presence in aqueous solution. These aggregates were solubilized by alkaline medium and micelar microenvironments of CTAB, SDS and Tween 20. H-aggregates were also responsible for the minor photobleaching rate constant and singlet oxygen formation by photosensitizers in an aqueous medium. Although, chlorins were about 15 times more efficient than hypericins on the singlet oxygen generation. The systematic analysis of photosensitizers photodynamic potential in Vero and HUVEC (non-tumor cells) and HEp-2 (tumor cells) was done using a factorial design combining the concentration of the photosensitizer, accumulation time of it into the cell and light doses. This analysis showed that the photosensitizer accumulation time is a significant parameter to eradicate selectively tumor cells. In contrast to non-tumor cells, in HEp-2 cells the accumulation rate was proportional of the lipophylicity of photosensitizer. The chemometric analysis resulted also in a mathematical model to estimate the half inhibitory concentration values. It had been statistical validated by comparing the experimental values determined for the photosensitizers. The hypericins have been more phototoxic to tumor cells than chlorines. In non-tumor cells derivatives were more cytotoxic than original compounds suggesting the use of these compounds for the selective inactivation of tumor cells. All these characteristics allow the use of these compounds as photosensitizers in photodynamic diagnostics and treatments.

Não existem normas internacionais que determinem limites aceitáveis de sorção de água e solubilidade para os materiais resilientes temporários para base de prótese, além de haver divergências metodológicas nos estudos. Objetivou-se avaliar de forma padronizada essas propriedades físicas para materiais macios de curta duração ao longo de sua vida útil. Corpos de prova (50mm x 0,5mm/ ISO-10139-2) de 7 condicionadores teciduais (Coe-Comfort-CC, Softone-ST, Rite-Line-RL, Dura Conditioner-DC, Hydro-Cast-HC, DentusoftDS e Visco-gel-VG) e 2 reembasadores resilientes temporários (Trusoft-TS e Coe-Soft-CS) foram individualmente confeccionados e submetidos à dessorção até estabilização das massas. Então, foram imersos em água destilada a 37oC por 3, 5, 7 ou 14 dias (n=10) para depois serem pesados, dessecados e pesados novamente. Os dados foram obtidos em porcentagens de sorção/solubilidade e analisados estatisticamente por ANOVA 2 fatores e teste de Tukey HSD (&#x3B1;=0,05). Em todos os períodos, VG (12,06±0,93 a 16,62±0,87%) apresentou a maior sorção de água dentre os materiais testados, sendo as menores porcentagens observadas para CC (2,23±0,53 a 2,99±0,49%) (P<0,05). CC, CS e TS não apresentaram alteração significativa da sorção de água ao longo de 14 dias (P>0,05). Já os demais materiais exibiram um aumento significativo da sorção de água entre os períodos de 7 e 14 dias (P<0,05). Para a solubilidade, valores médios inferiores e estatisticamente semelhantes foram apresentados pelos materiais DC, HC, DS, TS, RT e CS (0,28±0,30 a 2,13±0,23%) (P>0,05). ST (4,09±1,60 a 8,80±1,15%) demonstrou maior solubilidade que CC (1,89±0,30 a 3,35±0,70%), mas os mais altos valores percentuais dentre os materiais testados foram observados para VG (20,30±4,26 a 23,59±20,24%) (P<0,05). CC, DC, DS, HC, RT, TS e CS não apresentaram alterações na solubilidade percentual média ao longo dos 14 dias de avaliação. Já os condicionadores teciduais VG e ST exibiram aumento dos valores médios apenas aos 14 dias de imersão em água. Conclui-se que, ao longo da vida útil média de um condicionador tecidual (7 dias), os materiais CC, DC, HC, DS, RL, CS e TS apresentaram comportamento in vitro satisfatório em relação à sorção de água e solubilidade. De acordo com os resultados obtidos, os materiais CC, TS e CS foram considerados os mais indicados dentre os testados para reembasamento de próteses em até 14 dias. / There are no international standards that determine acceptable limits of water sorption and solubility for the temporary resilient liners, besides the differences in the methodology of the studies. It was aimed to evaluate in a standardized manner these physical properties of short-term soft materials throughout their lifespan. Specimens (50mm x 0.5mm/ ISO-10139-2) of 7 tissue conditioners (Coe-Comfort-CC, Softone- ST, Rite-Line-RL, Dura Conditioner-DC, Hydrocast-HC, Dentusoft-DS and Visco-gel- VG) and 2 temporary resilient liner (Trusoft-TS e Coe-Soft-CS) were individually prepared and submitted to desorption until mass stabilization. Afterwards, they were immersed in distilled water at 37oC for 3, 5, 7, or 14 days (n=10) to then be weighed, dried and reweighed. The data were obtained in percentages of sorption/solubility and statistically analyzed by 2-way ANOVA and Tukeys test (&#x3B1;=0.05). In all periods, VG (12.06±0.93 to 16.62±0.87%) showed the highest water sorption among the tested materials, with the lowest percentages observed for CC (2.23±0.53 to 2.99±0.49%) (P<0.05). CC, CS and TS showed no significant changes in water sorption over 14 days (P>0.05). The other materials exhibited a significant increase in water sorption between the periods of 7 and 14 days (P<0.05). For the solubility, lower (and statistically similar to each other) values were presented by DC, HC, DS, TS, RT, and CS materials (0.28±0.30 to 2.13±0.23%) (P>0.05). ST (4.09±1.60 to 8.80±1.15%) showed higher solubility than CC (1.89±0.30 to 3.35± 0,70%), but the highest percentages among tested materials were observed for VG (20.30±4.26 to 23.59±20.24%) (P<0.05). CC, DC, DS, HC, RT, TS, and CS showed no changes in the mean percentage solubility throughout the 14-day trial. The tissue conditioners VG and ST exhibited increased average values only at 14 days of water immersion. It was concluded that, over the lifespan of a tissue conditioner (7 days), the materials CC, DC, HC, DS, RL, CS, and TS presented suitable in vitro performance with respect to water sorption and solubility. According to the results, the materials CC, TS, and CS were considered best suited among the tested materials for denture relining of up to 14 days.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1981. / MICROFICHE COPY AVAILABLE IN SCIENCE AND ARCHIVES. Science copy in 2 v. / Vita. / Bibliography: leaves 320-331. / by Ronald Ted Kurnik. / Sc.D.

Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.

A talidomida (TLD) é um fármaco usado no tratamento de lesões associadas ao eritema nodoso leprótico, úlceras aftóides em pacientes HIV+/AIDS, algumas doenças crônico-degenerativas e mieloma múltiplo refratário à quimioterapia. Porém, apresenta problemas relacionados à sua farmacocinética, é pouco hidrossolúvel, e, por conseguinte, apresenta lenta e variável absorção no trato gastrintestinal. Uma proposta inédita que pode ser de interesse clínico é a formulação de uma dispersão sólida para a via oral, que permita a modulação da dissolução e biodisponibilidade da talidomida. O objetivo deste trabalho foi desenvolver e caracterizar dispersões sólidas (DS) contendo carreadores autoemulsionáveis e TLD, veiculado em cápsulas duras, a fim de melhorar as propriedades biofarmacêuticas do fármaco. Foram desenvolvidas formulações de TLD dispersa em Gelucire® (GEL) ou Kolliphor® (TPGS), associadas ou não a um adjuvante que em geral, diminui a recristalização de fármacos, a polivilpirrolidona (PVP K30). A técnica utilizada para preparar as DS foi o método de evaporação de solvente. A caracterização físico-química foi realizada por microscopia eletrônica de varredura (MEV), difração de raios-X (DRX), calorimetria exploratória diferencial (DSC) acoplada a células de aquecimento (Hot Stage), sugeriu formação de DS semicristalinas. A espectroscopia Infravermelha (IV), juntamente com DRX, demonstrou que a porção cristalina remanescente corresponde ao polimorfo α. A dissolução in vitro do fármaco a partir das DS foi significativamente melhor quando comparada ao fármaco isolado ou ao controle com amido. No tempo limite de 120 minutos, as DS tiveram percentual de dissolução em torno de 90%, enquanto o fármaco isolado de 50%, e o controle com amido de 70%. O estudo de solubilidade aquosa com diferentes excessos de fármaco foi realizado com o intuito de verificar se as DS eram capazes de manter o aumento da solubilidade aparente (estado de supersaturação) por um longo período de tempo. Foram obtidos incrementos da solubilidade aparente de até 3x superiores a do fármaco isolado, mas a capacidade solubilizante das DS mostrou-se saturável. Como conclusão, os resultados das análises físico-químicas, perfil de dissolução e solubilidade sugerem que a associação da talidomida com os carreadores autoemulsionáveis proporcionou melhora nas propriedades biofarmacêuticas da TLD, e criam perspectivas de investigação futuras, tais como a avaliação da permeabilidade intestinal in vitro. / Thalidomide (TLD) is a drug used for the treatment of lesions associated to the erythema nodosum leprosum, aphthous ulcers in HIV + / AIDS patients, some chronic diseases, and multiple myeloma refractory to chemotherapy. However, the drug is poorly aqueous soluble, and therefore presents slow and variable absorption in the gastrointestinal tract. An innovative proposal, which could be of clinical interest, is the formulation of oral solid dispersions, which allow modulation of dissolution, solubility, and, therefore, bioavailability of thalidomide. The objective of this study was to develop and characterize solid dispersions (DS) containing self-emulsifying carriers and TLD, filled in hard capsules, aiming to improve the biopharmaceutical properties of the drug. TLD has been dispersed in Gelucire® (GEL) or Kolliphor® (TPGS), associated or not to an excipient that usually decreases the drug recrystallization, polyvinylpyrrolidone (PVP K30). The technique used for preparing the DS was the solvent evaporation method. The physicochemical characterization by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) coupled to heating cells (Hot Stage), indicated the formation of semi crystalline DS. Infrared spectroscopy (IR), together with XRD, showed that the remaining crystalline portion corresponds to the polymorph α. The in vitro dissolution of the drug from the DS was significantly higher when compared to the drug alone, or the control with starch. At 120 min, the percentage of TLD dissolved from DS was around 90%, while drug alone showed 50% and drug+starch showed 70% dissolution. The aqueous solubility study performed with different drug excess assessed whether the DS were able to maintain the increase in apparent solubility (supersaturation state) for a long period of time. Increments around 3x were obtained in the apparent solubility, but the solubilizing ability of DS was found to be saturable. In conclusion, the results of physicochemical analysis, dissolution profile and aqueous solubility suggest that the association of thalidomide with self-emulsifying carriers provided improvement on the biopharmaceutical properties of TLD, and opened future research perspectives, such as the assessment of intestinal permeability in vitro.

The objective of this study is to investigate cocrystal solubility and dissolution behavior to elucidate the factors affecting these processes in various media. Six cocrystals with xanthines (theophylline (THP), caffeine (CAF) and theobromine (THB)) were prepared and characterized by powder X-ray diffraction and thermal methods. Two cocrystals (CAFCA I and THBSA) are new solids and their crystal structures were determined by single crystal X-ray diffraction. Cocrystal solubility behavior depended on the dissolving complex solubility and its dissociation behavior in solution. Two THP cocrystals - one with acetaminophen (ACE) and one with citric acid (CA) created different degrees of free THP supersaturation in solubility and dissolution studies. High transient THP supersaturation caused almost immediate THP hydrate crystallization from THPCAH and led to non-congruent solubility behavior. Such behavior was not observed with the ACETHP because free THP supersaturation was not sufficient to induce rapid crystallization but did so over longer equilibration times. Three salicylic acid (SA) cocrystals with xanthines (THP, CAF, and THB) were prepared; two (THPSA and CAFSA) had low aqueous solubility compared to their pure components and one (THBSA) had higher solubility. Both cocrystal components in these cocrystals produced higher solubility/dissolution rates in alkaline media due to ionization. Also, at higher pH, THB precipitated from THBSA solutions because of higher THB supersaturation under alkaline conditions. Caffeine (CAF) and theophylline (THP) both form cocrystals with citric acid (CA) which is a highly water-soluble cocrystal former. Both CAFCA Form I and II solubility and dissolution behavior were studied. THPCAH exhibited non-congruent dissolution because of rapid precipitation of THP hydrate on the dissolving cocrystal surface. CAFCA exhibited congruent dissolution because it did not produce sufficient supersaturation to precipitate CAF hydrate during dissolution. CA cocrystals also have the unusual behavior of high viscosities produced in the dissolution boundary layer due to CA’s high solubility. These viscosities alter diffusion coefficients which reduce dissolution rates from that expected based purely on solubility. To further understand cocrystal dissolution, a diffusion-convection-reaction (DCR) model was developed to predict cocrystal dissolution rates in various media. This model predicted concentration profiles of all species (complex, free components and reactive species) in the diffusion layer of a rotating disk intrinsic dissolution system. Predicted dissolution rates had varying degrees of agreement with experimental data depending on the cocrystal model and the medium into which the cocrystal dissolved.

One of the principal fertility problems of calcareous soils is the lack of available phosphates. The factors which control this availability are not completely understood. One hindrance to the solution of the problems involved results from confusion of the concepts of solubility and availability. Availability is the net effect of the chemical state of a plant nutrient element and the ability of the plant to utilize the forms of the element present under the existing chemical and physical environmental conditions. In this paper, the term solubility will be used to designate the chemical solubility of an element in water or in specified extracting reagents. The term physiological availability will be used to designate the ability of the plant to assimilate the soluble forms of the element, and the term net availability will be used to designate the net effect of chemical solubility and physiological availability. These limited definitions seem justified in this study because the sodium and calcium systems investigated are alkaline and plants growing in these systems would probably be largely limited to soluble phosphates. Solubility is known to be one of the main factors which control availability of phosphates, but there is now conclusive evidence as to the importance of physiological availability. Some investigators (26,13)1 have produced evidence which they claim supports the hypothesis that the H2PO4- ion is the only phosphate ion absorbed by plants. Since the relative concentration of this ion decreases as the pH increases above neutrality, they then conclude that physiological availability is largely a function of pH. Other investigators (41,7) have produced evidence which suggests that solubility is probably the only factor which limits the availability of phosphates in alkaline and calcareous soils. The purpose of this study is to add evidence which will help clarify the relative importance of solubility and physiological availability of phosphates in sodium and calcium soils.

Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly disease. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes is discussed in the first chapter of the dissertation. Convenient synthetic approaches to 3-aryl-4(1H)-quinolones via metal-catalyzed and metal-free arylation of β-keto carbonyl compounds is addressed in Chapter 2. A clean arylation protocol of ethyl acetoacetate was developed by using hypervalent diaryl iodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts varying in sterics and electronics was examined. This method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development. Additionally, a first gram scale synthesis of ELQ-300 and its structurally related 4(1H)-quinolone P4Q-391 using operationally simple and highly yielding metal-catalyzed conditions have been shown. Despite of 3-aryl-4(1H)-quinolone chemotypes displaying potent antimalarial activities against Plasmodium species in vitro and in vivo, their development is also associated with risks. 4(1H)-quinolones are known to be poorly soluble and thus represent challenging drug candidates for pharmacokinetic and bioavailability reasons. Disrupting of molecular crystal packing and prodrug approaches were employed to overcome solubility and bioavailability issues in current series. Quantum mechanics torsion profile calculations, 13C T1 spin-lattice relaxation experiments as well as X-ray studies were conducted with the objective to determine possible effects improving key physicochemical properties such as solubility and stability. As a backup strategy, a prodrug approach was developed enabling the 4(1H)-quinolone scaffold to be functionalized at the quinolone's oxygen. In order to avoid any enzymatic dependences, an approach was developed in which the prodrug moiety was removed via a pH-triggered decay. Additionally, phosphate prodrugs regenerating the active compound via extrahepatic enzymes such as the ubiquitous alkaline phosphatase were investigated. The development of orally bioavailable prodrugs enabled an advance overcoming in vivo efficacy limitations and has been confirmed by pharmacokinetic profiling studies. The herein presented approaches present viable options for any pyridone quinolone antimalarial chemotype which are currently studied.

Pulmonary and oral drug administrations are usually the preferred methods of delivery of active pharmaceutical ingredients.Generally,pulmonary drug formulations are more attractive compared to oral formulations since they consist of micron-sized powders with high surface area thus having faster onset of action,as well as minimizing the drug dosage and side effects.Oral insulin formulations,if achievable,would provide an alternative to injectable insulin,as the common drawbacks of injectable insulin are the multiple daily injections and the possibility of skin infections at the injection site. In this study,the feasibility of using dense gas particle processing techniques known as the Aerosol Solvent Extraction System (ASES),Gas Anti-Solvent (GAS)and High-Pressure Media Milling (HPMM)for pharmaceutical processing was assessed.The ASEStechnique,utilizing dense ethane,was employed to prepare insulin-lactose formulations for pulmonary administration whilst the GAS and ASES techniques,utilizing dense CO2,were employed to prepare microencapsulated formulations containing insulin and Eudragit?? S100 for oral administration.Furthermore,the HPMM technique,utilizing dense hydrofluocarbon (HFC)134a/227ea,was employed to prepare suspension Metered Dose Inhaler (MDI)formulations containing budesonide and various surfactants. The Fine Particle Fraction (FPF)of processed insulin without the presence of lactose was found to be 44%.In other words,44% of processed insulin delivered to the impactor stages (excluding the throat and neck)has aerodynamic diameter of less than 5??m.With the addition of lactose as carrier,the FPFof the insulin-lactose (1:1w/w)formulation increased to 64%.The increase in FPFwas attributed to the lower density of lactose particles compared to that of insulin particles to produce an intimate mixture with enhanced powder flowability and aerodynamic performance. Proteins for oral delivery should ideally be formulated with acid-resistant polymer as a protective coating to protect against enzymatic degradation in the stomach.Eudragit?? S100,which is insoluble or almost impermeable at pH 1-4and soluble at pH 5-7,was used to prepare oral insulin formulations.The insulin release at pH 3was sustained by the Eudragit?? S100coating and the encapsulation efficiency of insulin??Eudragit?? S100formulations varied between 6% and 24% depending on the initial drug to polymer ratio. One of the major therapies utilizing metered dose inhaler formulations in the treatment of asthma has been studied using the HPMM process.The HPMM process has been demonstrated to be an efficient milling process for the enhancement of the physical stability and aerodynamic performance of budesonide in HFC-134a/227ea propellant formulations.No significant change in physical stability was observed in the formulations for 2 weeks.

The dissolution profile of orally delivered drugs can be controlled through the use of osmotically controlled drug delivery devices. The most commonly used device is the osmotic tablet, which is essentially a tablet core that is coated with a rate-limiting semipermeable membrane. The feasibility of applying a coating onto a tablet using dense gas techniques was studied. Two different coating materials, polymethymethacrylate (PMMA, Mw = 120,000 g/mol) and cellulose acetate (CA, 39.8 wt% acetyl content) were applied onto an 8 mm osmotic tablet core using the Gas Anti-solvent (GAS) process. For PMMA, the pressurisation rate, coating temperature and volumetric expansion of up to 250% had minimal effect on the coating quality. The concentration, solvent type and the use of polyethylene glycol (Mw = 200 g/mol) had a more pronounced effect on the coating. The coating process was optimised to apply a smooth and uniform coating with a 50 ??m thickness. For CA, the pressurisation rate and the coating temperature had little effect on the coating that was applied. The process was more sensitive to a change in the concentration of the solution and the volumetric expansion that was used. It was found that the concentration could not be increased too much without affecting the coating quality. A CA coating was applied onto a PMMA-coated tablet using the optimised conditions. The thickness in the tablet coating increased by 10 ??m. Dissolution tests of the uncoated and coated tablets were carried out. The CA coatings were found to be insufficient in limiting the rate of water entering the tablet and performed similarly to an uncoated tablet core. The PMMA coatings were found to limit the rate of delivery of the model drug. However, variations in the PMMA coatings resulted in an inconsistent delivery profile across batches. The tablets coated with both PMMA and CA had a delivery rate in between that of uncoated and PMMA-coated tablets, indicating that the application of the second coating had compromised the initial PMMA coating.