The reformulation of pressurized metered dose inhalers (MDIs) with hydrofluoroalkanes (HFAs) from chlorofluorocarbons (CFCs) has given rise to many solubility challenges. Compounds and excipients previously used in CFCs were observed to have significantly different solubility values in HFA-134a. In this investigation, the solubility values of solid organic solutes were determined in pure HFA-134a and HFA-134a with cosolvent (0 - 20% w/w ethanol). The solubilities of solid solutes in HFA-134a were also compared with those in 2H,3H-decafluoropentane (DFP) in order to assess the suitability of DFP as a liquid model propellant. The experimental set of solutes display diverse physico-chemical properties and yielded solubility values that ranged over four orders of magnitude. The experimental solubilities were compared to calculated values obtained from ideal solubility and regular solution theory models. While the theoretical models did not offer absolute solubility estimations, a clear correlation with the ideal solubility (melting point) was noted. Further consideration utilizing multiple linear regression models afforded correlations based on molecular properties. Regression models, containing melting point and logP (or molar volume) resulted in promising correlations in both pure HFA-134a and HFA-134a/cosolvent systems where the average absolute errors ranged from 0.49 to 0.82 log units, (average factor errors of 3.09 and 6.61, respectively). In general, a linear relationship was observed between log mole fraction solubility in HFA-134a and fraction ethanol. The effect on solubilization ranged from 1.3 to 99.4 times when 20% w/w ethanol was introduced, relative to pure HFA-134a. DFP appears to be a promising liquid model for pure HFA-134a for pre-formulation calculations. A two parameter equation were found to be significant in pure HFA-134a where the average absolute error (AAE) value was 0.61 log units (average factor errors of 4.07).

Samples of ordinary copper, hot-isotactically-pressed (HIP) copper, and simulated borosilicate high-level waste glass were leached at 25°C, 51°C, and 80°C in solutions simulating brine and silicate groundwaters. It was found that the amount of glass leached increased at higher temperatures, and more leaching occurred in brine than in silicate groundwater. This behavior is predicted by Le Chatelier's Principle. Similarly, more copper was dissolved at higher temperatures, and more was dissolved in brine than in silicate groundwaters.

In most cases, organic materials exist in the solid phase as polymorphs, solvatomorphs or amorphous forms. Physico-chemical properties in the solid-state are all affected primarily in terms of dissolution, solubility, bioavailability, stability and processability. Therefore investigation into the polymorphic behaviour of APIs has become a mandatory part of drug characterisation studies by pharmaceutical companies (Giron, 2001). The influence polymorphism has on bioavailability and the need for the development of drugs in the amorphous form have instigated regulatory bodies such as the FDA to require solid-state characterisation of pharmaceuticals (Strachan et al., 2005). Subsequently a study was conducted to determine the physico-chemical properties of two poorly watersoluble macrolides; clarithromycin and spiramycin. Characterisation methods included: XRPD, IR, TGA, DSC, SEM, Karl Fischer titration, solubility and stability studies. Recrystallisations of spiramycin from various solvents indicated that this API mainly exists in the amorphous form. The DSC proved to be of little value in the characterisation of this particular macromolecular antibiotic, since wide inter-sample variations were mostly obtained. TGA results showed higher solvent uptake than expected. This was ascribed to the amorphous, sponge-like character of this drug. For the sake of reproducibility and quality of the results, characterisation of spiramycin was more reliant on spectroscopic and crystallographic methods. Samples generated from 2- butanol, chloroform, ethyl acetate, 1.4-dioxane, methanol, n-propanol, iso-propanol and tetrahydrofuran showed characteristic peaks in the range of 2000-2400 cm-1 that were not present in the IR spectrum of the raw material. Conversely, the XRPD patterns were all identical, exhibiting a characteristic “halo” pattern with no detectable Bragg diffraction peaks. A solubility assessment showed no significant differences between the raw material and the recrystallisation products. In fact the raw material seemed to be the form with the highest solubility, albeit it only by a small margin. According to the literature, clarithromycin exists in five forms. Form 0 exists as a solvate, form I is a metastable form, form II is the stable form (Liu & Riley 1998; Deshpande et al., 2006), form III is a solvate of acetonitrile (Liu et al., 2003; Liang & Yao, 2008) and form IV is a hydrate (Avrutov et al., 2003). The stable form II is used in formulations currently on the market. A follow-up study was done relating to a study performed by De Jager (2005). The raw material (form II) was recrystallised from acetonitrile, chloroform and ethyl acetate. Two new crystal forms were prepared from chloroform and acetonitrile. With the necessary driving force, both of these crystals forms are able to convert to the thermodynamically stable form II. In addition, a solvate recrystallised from chloroform together with its corresponding desolvate, showed a 4 and 1.5 fold respective increase in solubility when compared to the raw material. The recrystallisations from ethyl acetate delivered crystals with an XRPD pattern similar to form II. This proved that clarithromycin can be recrystallised directly from this solvent without the need of an additional conversion step, as was the case in the study done by De Jager (2005). / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2013

Dissertation research involves development of Mobile Order Theory thermodynamic models to mathematically describe and predict the solubility, spectral properties, protonation equilibrium constants and two-phase partitioning behavior of solutes dissolved in binary solvent mixtures of analytical importance. Information gained provide a better understanding of solute-solvent and solvent-solvent interactions at the molecular level, which will facilitate the development of better chemical separation methods based upon both gas-liquid and high-performance liquid chromatography, and better analysis methods based upon complexiometric and spectroscopic methods. Dissertation research emphasizes chemical equilibria in systems containing alcohol cosolvents with the understanding that knowledge gained will be transferable to more environmentally friendly aqueous-organic solvent mixtures.

Satellite precursor cells are normally quiescent but once activated they support skeletal muscle growth and regeneration by proliferating and differentiating into myoblasts. When an animal suffers from a muscle injury, quiescent satellite precursor cells are activated by nitric oxide (NO). MyoNovin (1-(3,4-Bis-nitrooxy-butoxy)-2-methoxy-benzene), as a NO donor, was developed to provide nitric oxide directly to the skeletal muscle and has been shown to promote satellite cell activation. A potential drawback of the current MyoNovin molecule is its poor water solubility. The aim of this work was to enhance the water-solubility of MyoNovin in order to improve its ease of formulation and possibly enhance its biological activity. The structure of MyoNovin (MN1) was modified with three different functional groups - methanesulfonyl (MN2), benzoic acid (MN3) and acetamide (MN4). The three novel MyoNovin analogs were identified and shown to have similar biological activity as with MyoNovin. All three MyoNovin analogs were found to have better water solubility.#Based on these results, two of the MyoNovin analogs (MN2 and MN3) had much better biological activity with respect to satellite activation and much improved water solubility and may be the most promising candidates for future studies. / May 2015

Adesivos modernos são misturas complexas de monômeros resinosos hidrofílicos e hidrofóbicos dissolvidos em combinações de água/solvente. A inclusão de monômeros altamente hidrofílicos nos sistemas adesivos está transformando-os em membranas permeáveis que são altamente susceptíveis aos efeitos de degradação da água. Desenvolver formulações adesivas que promovem uma melhor penetração de componentes hidrofóbicos dentro da matriz dentinária é de grande importância. O método mais válido para se avaliar o processo de degradação in vitro é a armazenagem dos espécimes em água. Neste estudo avaliamos através do microcisalhamento com delimitação da área adesiva de 0,8 mm, a resistência adesiva de 3 adesivos experimentais com diferentes graus de hidrofilia. Os fatores de variação foram 2: o tipo de adesivo experimental utilizado, em 4 níveis ( Bis-GMA, Bis-EMA/ Bis-GMA, PBH, Single Bond) e o período de armazenamento, em 3 níveis (1 dia, 7 dias, 90 dias), totalizando 12 níveis de variação. Foram confeccionadas 120 superfícies de dentina de 30 terceiros molares extraídos, totalizando um n= 10. O modelo estatístico escolhido foi o teste paramétrico de ANOVA de dois fatores independentes. Os adesivos experimentais apresentaram valores na faixa de 11.31 a 12.96 MPa, sendo que o PBH apresentou os menores valores de resistência adesiva, Bis-GMA os maiores e Bis-EMA/Bis-GMA valores intermediários, enquanto que o grupo Controle está dentro de uma faixa média de 24 MPa. Através da MEV, observamos que os adesivos experimentais não formaram camada híbrida, embora tenha ocorrido a penetração nos túbulos dentinários e a formação de tags de resina. Provavelmente, a menor hidrofilicidade dos adesivos não permitiu a penetração dos adesivos na matriz de colágeno úmida para provocar uma hibridização levando a resistências adesivas bem menores que o adesivo controle. Com o presente estudo, concluímos que adesivos dentinários com componentes monoméricos hidrofóbicos, embora formem tags de resina, se tornam incapazes de penetrar nas fibras colágenas e formar camada híbrida e consequentemente têm baixa resistência adesiva e que também tende a decair com o tempo. / The most recent adhesives systems have fewer steps required for bonding to simplify use and hopefully reduce technique sensitivity. A trend in adhesive dentistry is providing simpler and faster adhesives. Single bottle adhesives are complex mixtures of hydrophilic and hydrophobic resin monomers dissolved in water/solvent combinations. In this study we evaluate by microshear test 3 experimental adhesives with different degree of hydrophilicity after 1, 7 and 90 days.The variation factors were 2: the type of the adhesive used, at 4 levels (Bis-GMA, Bis-EMA/Bis-GMA, PBH, Single Bond) and the period of storage, in 3 levels (1 day, 7 days, 90 days), totalizing 12 levels of variation. The etch-and-rinse experimental adhesive systems were formulated by FGM, Joinville, SC, BR. The experimental units were confectioned on 120 dentine surfaces of 30 third extracted molar, totalizing n= 10. The specimens were stored in water distilled and divided in 4 groups of 10 specimens in accordance with the type of used monomer, being that each tooth origin 4 specimens. The delimitation of the adhesive area was used, made with adhesive ribbon double face with 1 circular perforation lined up of 0,8 mm of diameter made with a rubber sheet perforator in each specimen, being used for each one tygon tubing with light of 0,8 mm. The fractures were classified as adhesive, coesive in dentine, coesive in resin and mixing. Using the parametric test of variance analyses (ANOVA) of two independent factors, we observed that the experimental adhesives showed values in the range of 11.31 a 12.96 MPa, as the PBH showed the lowest values of resistance, Bis-GMA the highest and Bis-EMA/Bis-GMA intermediary values, and the control group in the range of 24 MPa. Dentin adhesives with hydrophobic monomeric components can form resin tags, but they are disable to penetrate colagen fibers and form hybrid layers and consequently have low bond resistance that falls with time.

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.

No processo de obtenção de níquel de fontes de minério limonita, a lixiviação ácida do minério resulta na dissolução de íons metálicos em uma solução aquosa. Com o uso da tecnologia apropriada, é possível recuperar esses íons metálicos em vez de descartá-los. O presente estudo tem como objetivo a recuperação de magnésio de uma solução contendo íons magnésio e sulfato utilizando-se a técnica da cristalização a alta temperatura. A aplicação da cristalização a alta temperatura para recuperar o magnésio na forma de sulfato de magnésio hidratado pode ser vantajosa uma vez que sua decomposição térmica resulta em MgO e SO2, produtos que podem ser reutilizados no processo de mineração da limonita. Isso reduz o volume de resíduo formado e custo de reagentes no processo. Foi projetado um sistema de cristalizador acoplado a filtração e foi verificado a influência da temperatura, tempo de residência e pH da solução na quantidade de magnésio cristalizado. A solução residual de cada batelada foi analisada por cromatografia de íons para quantificar o magnésio na solução. Os cristais formados foram analisados utilizando-se a técnica de difração de raios-X (DRX), por microscopia eletrônica de varredura (MEV-EDS) e agitamento de peneiras a fim de avaliar a composição química, morfologia e granulometria dos cristais. A solubilidade do sulfato de magnésio foi determinada experimentalmente com o intuito de ampliar a compreensão da solubilidade do sal e obter valores de Kps. Em 5 horas de tempo de residência o sistema foi estabilizado, indicando que não haverá mais crescimento cristalino em tempos de residência maiores que 5 horas. Em pH 5,7 a 230°C e em 5 horas de tempo de residência ocorreu a maior remoção de magnésio com cerca de 81% cristalizado. Os cristais apresentaram morfologia esférica com exceção do cristal obtido a 230 °C em pH 2, que apresentou formato retangular. A análise por DRX mostrou a presença de um produto constituído majoritariamente por sulfato de magnésio monohidratado. / In the process of obtaining nickel from sources of limonite ore, the acid leaching of the ore results in the dissolution of metallic ions in solution. With the use of appropriate technology, it is possible to recover these metal ions instead of discarding them. The present study aims to recover magnesium from a solution containing magnesium and sulfate ions using high temperature crystallization. The application of high temperature crystallization to recover magnesium in the form of hydrated magnesium sulfate may be advantageous since its thermal decomposition results in MgO and SO2, products which can be reused in the limonite mining process. This reduces the volume of waste formed and the cost of reagents in the process. A crystallizer coupled to a filtration system was designed and the influence of the temperature, residence time and pH of the solution on the amount of crystallized magnesium from solution was investigated. The residual solution was analyzed by ion chromatography to quantify the magnesium in the solution. The crystals formed were analyzed by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM-EDS) and sieve shakers in order to evaluate the chemical composition, morphology and grain size of the crystals. The solubility of magnesium sulphate was determined experimentally to increase the understanding of the solubility of the salt and obtain values of Kps. In 5 hours of residence time the system was stabilized, indicating that there will be no more crystalline growth at residence times greater than 5 hours. At pH 5.7 at 230 ° C and in 5 hours of residence time 81% of Mg crystallized. The crystals presented spherical morphology except for crystals obtained at 230 °C, at pH 2, which presented a rectangular shape. XRD analysis showed the presence of a product consisting mainly of magnesium sulphate monohydrate.

A nimesulida é um fármaco pertencente à classe terapêutica dos compostos antiinflamatórios não esteróides (AINES), agentes farmacológicos muito utilizados pela população brasileira. Este fármaco possui a propriedade de inibir seletivamente a enzima ciclooxigenase do tipo II (COX-2), uma das responsáveis pela proteção tecidual e redução dos efeitos adversos da maioria dos antiinflamatórios, tais como a gastropatia e a nefropatia. Esta característica de seletividade confere a nimesulida vantagens em relação aos AINES não seletivos. Trata-se de um fármaco praticamente insolúvel em água que está enquadrado no grupo II do Sistema de Classificação Biofarmacêutico (SCB). Diante do exposto, os objetivos deste trabalho foram a obtenção e a caracterização de dispersões sólidas do fármaco nimesulida, mediante a utilização de polímeros hidrossolúveis (PVP, plasdone S630 e poloxamer P188 e P407). As dispersões sólidas foram obtidas pelo método da evaporação da solução de solventes acetona:etanol (1:1) utilizados para a solubilização da nimesulida e polímeros, respectivamente, mediante a utilização de rota-vapor à temperatura não superior a 45°C e pressão reduzida. A caracterização da nimesulida e das dispersões sólidas obtidas foi realizada utilizando-se as seguintes técnicas: difratometria de raios X; espectroscopia de absorção na região do infravermelho; técnicas termoanalíticas, como, calorimetria exploratória diferencial (DSC) e termogravimetria (TG); microscopioa eletrônica de varredura (MEV) e difratometria a laser para a determinação do tamanho de partículas. A nimesulida utilizada na preparação das dispersões sólidas demonstrou mudança de hábito cristalino após a obtenção das dispersões sólidas. A avaliação da solubilidade da nimesulida e das dispersões sólidas obtidas foi determinada por meio do método do equilíbrio e avaliação espectrofotométrica. Os resultados demonstraram que a a formação das dispersões sólidas implica: na prevalência das características do polímero sobre as características da nimesulida, que aumenta à medida que a proporção de polímero é aumentada; na alteração do perfil de difração de raios X da nimesulida, tornando o perfil difratométrico da dispersão sólida mais semelhante ao do polímero; na mudança do comportamento térmico (curvas de DSC e TG) ; e na possível mudança do hábito cristalino da nimesulida Adicionalmente, os resultados dos ensaios de solubilidade permitiram demonstrar o aumento solubilidade da nimesulida em todas as preprações de dispersões sólidas obtidas, sendo que para as dispersões sólidas que utilizaram os polímeros poloxamer P188 e P407, observou-se que incremento na solubilidade foi de até quatro vezes se os valores forem comparados com a solubilidade da nimesulida pura. / Nimesulide belongs to the therapeutical class of the non steroidal anti-inflammatory drugs (NSAID) and it´s considered to be very used by the Brazilian population. Nimesulide has the property to inhibit selectively the ciclooxigenase enzyme (COX-2), one of the responsible for the tecidual protection and the reduction of the adverse effect, such as gastropatia and nefropatia. The selective characteristic confers to nimesulida advantages in relation to the not selective NSAIDs. Nimesulide is practically insoluble in water and it´s been classified as group II in the Biopharmaceutical Classification System (BCS). The objectives of this study had been the attainment and the characterization of nimesulide solid dispersions by means of hydrosoluble polymers used as carriers as (pvp, plasdone S630 and poloxamer P188 and P407) in acetone:ethanol solution (1:1).The solid dispersions have been obtained by the evaporation method, using route-vapor at maximum temperature of 45°C and under reduced pressure. The characterization of the nimesulide dispersions was carried by using the following techniques: X- rays difratometry; spectroscopy of absorption in the region of the infra-red ray; thermoanalytical techniques as differential scanning calorimetry (DSC) and thermogravimetry (TG); scanning eletronically microscopy (SEM) and laser difratometry for the particle size determination. The evaluation of the solubility of the nimesulide and the respective solid dispersions was determined by means of the equilibrium method and spectrophotometric evaluation. The results have demonstrated that the preparation of solid dispersions implies: the prevalence of the characteristics of polymer on the characteristics of the nimesulide, which increases with the increase of the carrier quantity in the solid dispersion; the modification of the difratometry profile that shows to acquire some polymer profile characteristics; the change of the thermal behavior (curves of DSC and TG); and the possible change of the crystalline habit. Additionally, the results of the solubility assays for all preparation have allowed to demonstrate the increase of the nimesulide solubility. The solid dispersion containing polymer carrier P188 and P407 have demonstrated the largest solubility results reaching up to four times if compared to the solubility of the pure nimesulida.

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2015. / Solvatomorphism of an active pharmaceutical ingredient (API) is one of the most studied areas in pharmaceutical science. Since APIs are exposed to solvents during many stages of their production, knowledge of the consequences from such exposure is essential. Salt formation has been known to improve some physicochemical properties of an API. Amongst these properties, API solubility is one of the most important characteristics as their use in the market is determined by this feature. Research presented here investigated the solvates and salts of mefenamic acid (MA) and tolfenamic acid (TFA); both representing fenamic acids belonging to a class of non-steroidal anti-inflammatory drugs (NSAIDs). Solvates were obtained by reactions of TFA and MA with the solvents 2-picoline, 3-picoline, 4-picoline, 3-bromopyridine and 3-chloropyridine. A solvate polymorph of MA and 2-picoline was isolated. The salts were obtained by using diethanolamine, ethylenediamine, 1-methylpiperazine, and triethylamine in combination with the fenamic acids. Morpholine formed a salt with TFA, but not with MA. Instead a zwitterionic form of MA was synthesised when the latter was mixed with morpholine. The resulting compounds were characterised and their crystal structures analysed. It was found that the conformation of the acids in the solvate and the salt compounds differed. Moreover, within the solvates, the conformation of the fenamate backbone varied depending on the acid and the solvent used for crystallisation. Although similar solvents were utilized, the structural packing arrangements of TFA solvates were very different from the arrangements associated with MA. The thermal analyses of the salts/solvates were determined by using both thermogravimetry and differential scanning calorimetry. The compounds were further investigated after manual grinding and the preparation of slurries. These preparation methods were successful for most compounds but not for MA•2PIC and (MA-)(EDM+). Instead, the recrystallization, grinding and slurry investigations of MA•2PIC yielded a polymorph of this particular solvate. In the case of (MA-)(EDM+), the PXRD results obtained from both the pulverised and slurry samples were completely different from one another and also from those determined for the starting materials. Generally, the desolvation studies of the MA salts and solvates produced the same crystal form as occurred in the starting material. The exception was (MA-)(TA+) wherein desolvation produced a mixture of two polymorphs of MA.