Yes / Sonochemistry, i.e., the application of mechanical energy in the form of sound waves, has recently been recognised for its similarity to mechanochemistry and is now included under the umbrella term of mechanochemistry. Typically, due to the hypothesised cavitation mechanism, a liquid medium is considered as a necessity for a process to take place as a result of ultrasonic irradiation. In view of this, condensation reactions between solid reagents in the complete absence of solvent were carried out successfully by ultrasonic irradiation with the importance of particle size being highlighted. This work increases the potential of sonochemistry in the drive towards a sustainable future. / EPSRC (EP/L019655/1)

No description available.

Co-crystals are emerging as a potential area in the field of crystal designing as it improves material's physicochemical properties. Many groups are working on the development of newer techniques for the preparation of co-crystals, which can be scalable and contribute to the green agenda. Being continuous and scalable technique, our own developed twin screw extrusion mediated solvent free continuous co-crystallisation (SFCC) technique has been used for the preparation of carbamazepine: saccharin co-crystal. Carbamazepine has been used as a model drug since it shows challenges such as low solubility (BCS class II), polymorphism and thermolabile nature whilst, saccharin was used as a co-former. Effect of extrusion processing parameters such as shear, temperature and screw speed on cocrystallisation has been studied. In addition to this, effect of particle size of co-crystal components, use of hydrated form of carbamazepine, addition of solvent and application of reverse elements on the purity of co-crystal was understood. Use of carbamazepine dihydrate as a starting component yields pure co-crystals. The addition of small amount of polar solvent in anhydrous carbamazepine also yields pure co-crystals whereas particle size did not show any significant effect. Result showed that selection of processing temperature near to eutectic, moderate shear and increase in residence time of component mixture in mixing zone was mainly responsible for co-crystallisation. The extrudates were mainly characterised by XRPD, DSC and in-vitro dissolution tests. Pure co-crystals prepared by addition of highly Development of a solvent free continuous co-crystallisation technique for carbamazepine-saccharin ii polar solvent have been showed drug release identical to that of pure co-crystals prepared by solvent crystallisation.

Microwave hydrodiffusion and gravity (MHG) technique is an attempt towards development of green extraction, as this environment friendly technique has completely eliminated the use of organic solvents. After describing the effectiveness of microwave radiations in extraction field in the first part of this manuscript, we have optimized this noval extraction method to get antioxidants rich extract. Along with studying the temperature distributions in different parts of plant material under the effect of microwave irradiations, we have analyzed the influence of microwaves in enhancing the antioxidant activity of extracts by using different tests. We have got the promising results concerning about the antioxidant rich extracts of different onion varieties and sea buckthorn in generalization step against the conventional solvent extracts. The application of vacuum system in this extraction system helped in restraining the limitations like dry extract yield and flavonol contents. Incomparison to traditional and recent extraction systems, the MHG extracts doesn’t require any filtration and purification steps as it works in absence of any solvent and water and are highly recommended for direct application in industrial products / L'hydrodiffusion générée par micro-ondes est une nouvelle technique d'extraction mise au point au sein de l'Université d'Avignon et des Pays de Vaucluse. Ce procédé est une combinaison entre une technique traditionnelle et une technologie innovante. En effet, le chauffage par micro-ondes a permis d'initier et de générer le transfert de matière et de chaleur de l"intérieur des matrices végétales (oignons) vers l'extérieur et de réduire de façon considérable les temps d'extraction des antioxydants sans aucune intervention de solvant. A titre de comparaison, les polyphénols de différentes variétés d'oignons ont été extraits par l'hydrodiffusion générée par micro-ondes et par la technique conventionnelle, l'extraction par solvant. Les rendements obtenus par micro-ondes sont presque identiques à ceux obtenus à l'aide d’un solvant alors que les temps d'extraction sont réduits. La capacité antioxydante des extraits micro-ondes est supérieure à celle obtenue par technique conventionelle. Ce qui présage des potentialités d'application dans le domaine agroalimentaire en particulier pour la valorisation des co-produits. Une étude cinétique de l'extraction, ainsi qu'une observation au microscope optique(cytologie) des matrices traitées soumises aux micro-ondes et au solvant ont mis en évidence la spécificité de l'extraction sans solvant assistée par micro-ondes au niveau des mécanismes de libération et d'extraction des molécules antioxydantes au sein du végétal. L'effet des micro-ondes a pour conséquence une libération plus rapide des principes actifs contenue dans la plante grâce à l'ouverture quasi instantanée des glandes et l'explosion des cellules. L'explication de la différence de composition chimique entre les procédés d'extraction par solvant et par micro-ondes pourrait être basée principalement sur des phénomènes de solubilité, de polarisation diélectrique ainsi qu'un transfert de matière et de chaleur inversé

Abstract will not load on to DSpace

Current research focuses on the effect of different continuous solid state shear based processing for the production of pharmaceutical amorphous system and cocrystals for poorly water soluble APIs. The S3M technology is getting first time reported for its application in pharmaceutical field and it is considered as technology with good potential for development of pharmaceutical dosage forms. The main objectives of this study include the effect of two solid state shear processes on the product properties in case of solid dispersions and cocrystals. Hot melt extrusion technology has been widely explored for the production of pharmaceutical solid dispersions and cocrystals, it would be helpful to compare how the new invented S3M technology will differ from the existing solid state shear process. The S3M has been also explored for the advantages over HME process in terms of residence time, plasticiser free dispersions, effect of process on degradation of drugs during processing. For this purpose, the process and material modifications during operation of these two technologies was important aspects of this study. The pharmaceutical drugs chosen for the solid dispersion purpose were carbamazepine, ibuprofen, glibenclamide which are BCS class II drugs and paracetamol from BCS class III drug was selected as model drug for solid dispersion manufacturing with PVP. VA64, HPMCP HP55, HPMCAS, Ethyl cellulose as polymers. In case of cocrystals selected drugs were carabamazepine, caffeine, paracetamol and ibuprofen with co-formers nicotinamide, saccharin, salicylic acid, glutaric acid, oxalic acid, maleic acid. The selections of co-formers were done on the basis of functional group complementarity between drug and co-former. All the details about the pairs for cocrystals and for solid dispersions are given in experimental section. Carbamazepine has been explored in depth for solid dispersions with different polymers and with different co-formers in case of cocrystals. The effect of process variables and amount of shear applied during processing was deciding factor in product output and quality. The end product in case of both the solid dispersions and cocrystals varied in their physicochemical, morphological and drug release properties HME process needed addition of plasticisers during preparation of solid dispersions whereas S3M was plasticiser free process which gave good insight on how this will affect the product performance during evaluation studies. The solid dispersions in case of HME were had smooth surfaces and which are non-porous in nature whereas in case of S3M the solid dispersions were highly porous in nature. The differences in the structural and morphological features of solid dispersions somehow did not affect the drug release of drug during in-vitro dissolution studies and both the solid dispersions did not show much difference in drug release. In case of cocrystals processing on S3M it was observed that the S3M process is dependent on the use of polymer as process aid. For this purpose PEO, PVP VA64 and HPMCP HP55 were selected as model polymer as process aid during processing of cocrystals, out of which PEO has been explored widely as processing aid due to its process suitability, low melting and ability to withstand high shear during processing. PVP VA64 was used only in case of carbamazepine cocrystals with salicylic acid and HPMCP HP55 in case of caffeine cocrystals with maleic acid. The effect of concentration of PEO in case of carbamazepine cocrystals as processing aid was studied (concentration range 5%, 10%, 15%, 25% w/w). The concentration of PEO in case of HME cocrystals had direct effect on the drug release of drug dissolution studies which was reduced in case of higher concentration of PEO (25% w/w), which was not observed in case of S3M processes carbamazepine cocrystals. The product in case of cocrystals by S3M was thread like structures whereas in case of HME cocrystals were in form of screw shaped compact mass. The difference in morphological and structural properties of cocrystals did not had major effect on drug release in case of S3M process but in case of HME processed cocrystals the higher amount of polymer slowed the drug release. The degradation studies in case of drugs carbamazepine, paracetamol were carried out whereas in case of polymer for HPMCP HP55 were carried out. It was found that HME processed samples showed higher degradation as compared to S3M processed one in both the cases solid dispersions and cocrystals. This can be attributed to high residence time in case of HME as compared to S3M process. The effect of two high shear processes HME and S3M had significant effect on the morphological and structural properties of the solid dispersions and cocrystals. The variation in the structural and morphological properties did not have direct effect on the drug release of drug during dissolution studies. HME and S3M both the processes had some positive and some negative aspects within them for processing of pharmaceutical dispersions and cocrystals. In case of HME the use of plasticiser is mandatory to maintain low torque levels during processing and to avoid blockage of extruder barrel, whereas in case of S3M the process is plasticiser independent and processing of solid dispersion is very easy as compared to HME with low residence time. Processing of plain drug or co-former was easy in case of HME whereas in case of S3M processing it was mandatory to use polymer as processing aid specially during processing of cocrystals. In case of process controls HME has excellent control over the process parameters which can be controlled and manipulated as per requirement, whereas S3M technology needs to have technical modifications to have better control over its processing parameters. The S3M can be a revolutionary technology for pharmaceutical industry once it is upgraded with better control and optimised process parameters.

As nontoxic biobased surfactants derived from plant oils and cellulose or starch, saccharide-fatty acid esters are widely used in cosmetics, food, and pharmaceutical industries due to their biocompatibility, biodegradability as well as antimicrobial activity. Generally, saccharide-fatty acid esters are synthesized chemically under high pressure, temperature and the presence of alkaline or acid catalysts leading to low-quality products (chemo-degradation of double bonds and oxygenated moieties) and large amounts of byproducts. In contrast, biocatalytic synthesis enhances sustainability: near-ambient pressure and temperature, the absence of toxic, acids and bases catalysts, and improved selectivity of products. For lipase-catalyzed synthesis under nearly anhydrous conditions, the major hurdle to be overcome is the poor miscibility of the acyl donor and acceptor substrates, resulting in slow reaction rates. Although several approaches such as, the employments of organic solvents, complexation agents, and ionic liquids, have been reported in the literature, a robust solution is desperately needed. This study focused on employing immobilized lipases under completely solvent-free conditions to synthesize saccharide-fatty acid esters using the ester products to enhance miscibility. Experimentally, metastable saccharide particles with a diameter of 10-100 micron-sized suspensions of saccharide were formed in oleic acid-rich ester mixtures initially for synthesis of saccharide-fatty acid esters in packed bed bioreactor containing immobilized lipases. Water, a by-product that limits ester yield by promoting hydrolysis, was removed via free evaporation. In this dissertation, a bioreactor system was developed for the eco-friendly solvent-free, immobilized lipase-catalyzed synthesis of biobasaed surfactants utilizing suspensions as reaction medium with 88 wt% in 6 days; the performance of the bioreactor systems developed for Objective 1 was optimized through water concentration control and interval time with 91 wt% in 4.8 days; and to improve design of bioreactor system developed in Objective 1 by in-line filter and derive a mathematical model to describe the production of esters by the bioreactor systems developed. Finally, 84 wt% ester content was achieved in 8.4 days.

The direct catalytic hydrogenation of nitrile butadiene rubber (NBR) in latex form was studied as a model system for the development of a new latex hydrogenation process for the modification of unsaturated diene-based polymers. NBR is a synthetic rubber of copolymerized acrylonitrile and butadiene produced in latex form by emulsion polymerization. The catalytic hydrogenation of NBR is an important post-polymerization process resulting in a more stable and tougher derivative, hydrogenated NBR (HNBR), which has been widely used in the automotive and oil drilling industry. The present commercial process involves a number of cumbersome steps to obtain solid NBR from the latex and subsequent dissolution of the solid NBR in a large amount of organic solvent followed by solvent recovery after coagulation of the hydrogenated NBR. Since NBR is produced in latex form, it is very desirable to directly hydrogenate NBR in the latex form which will significantly simplify the hydrogenation process and facilitate subsequent applications. As an economical and environmentally benign alternative to the commercial processes based on the hydrogenation of NBR in organic solution, this direct latex hydrogenation process is of special interest to industry. The objective of this project is to develop an efficient catalytic system in order to realize the direct catalytic hydrogenation of NBR in latex form. OsHCl(CO)(O2)(PCy3)2 was initially used as the catalyst to investigate the possibility of hydrogenation of NBR in latex form and to understand the major factors which affect the hydrogenation operation. It was found that an organic solvent which is capable of dissolving or swelling the NBR was needed in a very small amount for the latex hydrogenation using the Os catalyst, and gel occurred in such a catalytic system during hydrogenation. Wilkinson’s catalyst, RhCl(PPh3)3, was then used for the latex hydrogenation in the presence of a small amount of solvent successfully without gel formation. Further investigation found that Wilkinson’s catalyst has a high activity for NBR latex hydrogenation without the use of any organic solvent. The influences of various operation conditions on hydrogenation rate, such as catalyst and polymer concentrations, latex system composition, agitation, reaction temperature and hydrogen pressure, have been investigated. It was found that the addition of triphenylphosphine (TPP) has a critical effect for the hydrogenation of NBR latex, and the hydrogenation rate was mainly controlled by the amount of catalyst which diffused into the polymer particles. In the presence of TPP, NBR latex can be hydrogenated to more than 95% degree of hydrogenation after about 30 hours at 160oC using Wilkinson’s catalyst with a catalyst to NBR rubber ratio of 1 wt%, without the addition of any organic solvent. The apparent activation energy for such NBR latex hydrogenation over the temperature range of 152oC to 170oC was found to be 57.0 kJ/mol. In the present study, it was also found that there are some impurities within the NBR latex which are detrimental to the hydrogenation reaction and are suspected to be water-soluble surfactant molecules. Deliberately designed solution hydrogenation experiments were conducted to study the impurity issue, and proper latex treatment methods have been found to purify the latex before hydrogenation. To improve the hydrogenation rate and to optimize the latex hydrogenation system, water soluble RhCl(TPPMS)3 catalyst (TPPMS: monosulphonated-triphenylphosphine) was used for the latex hydrogenation of NBR. The latex hydrogenation using the water soluble catalyst with TPP can achieve more than 90% degree of hydrogenation within 20 hours at 160oC. Further experiments using RhCl3 with TPP proved that the water soluble RhCl3 can be directly used as a catalyst precursor to generate the catalytic species in situ for the latex hydrogenation, and a stable NBR latex with 96% degree of hydrogenation can be produced without any gel problem within 19 hours of reaction at 160oC. The catalyst mass transport processes for these Rh based catalysts in the latex system were investigated in order to further optimize the solvent-free latex hydrogenation process. While maintaining the emulsified state of the original latex, the direct catalytic hydrogenation of NBR latex can be carried out efficiently without any cross-linking problem to more than 92% degree of hydrogenation within 8 hours at 160oC. As a result of this research project, new latex hydrogenation technologies were successfully developed to fulfill all major requirements for a solvent-free polymer latex hydrogenation route, which is a significant milestone for the improvement of this polymer modification technology. The finding of TPP’s role as the “catalyst mass transfer promoter” is a breakthrough for the research field related to the hydrogenation of unsaturated diene-based polymers in latex form.

The direct catalytic hydrogenation of nitrile butadiene rubber (NBR) in latex form was studied as a model system for the development of a new latex hydrogenation process for the modification of unsaturated diene-based polymers. NBR is a synthetic rubber of copolymerized acrylonitrile and butadiene produced in latex form by emulsion polymerization. The catalytic hydrogenation of NBR is an important post-polymerization process resulting in a more stable and tougher derivative, hydrogenated NBR (HNBR), which has been widely used in the automotive and oil drilling industry. The present commercial process involves a number of cumbersome steps to obtain solid NBR from the latex and subsequent dissolution of the solid NBR in a large amount of organic solvent followed by solvent recovery after coagulation of the hydrogenated NBR. Since NBR is produced in latex form, it is very desirable to directly hydrogenate NBR in the latex form which will significantly simplify the hydrogenation process and facilitate subsequent applications. As an economical and environmentally benign alternative to the commercial processes based on the hydrogenation of NBR in organic solution, this direct latex hydrogenation process is of special interest to industry. The objective of this project is to develop an efficient catalytic system in order to realize the direct catalytic hydrogenation of NBR in latex form. OsHCl(CO)(O2)(PCy3)2 was initially used as the catalyst to investigate the possibility of hydrogenation of NBR in latex form and to understand the major factors which affect the hydrogenation operation. It was found that an organic solvent which is capable of dissolving or swelling the NBR was needed in a very small amount for the latex hydrogenation using the Os catalyst, and gel occurred in such a catalytic system during hydrogenation. Wilkinson’s catalyst, RhCl(PPh3)3, was then used for the latex hydrogenation in the presence of a small amount of solvent successfully without gel formation. Further investigation found that Wilkinson’s catalyst has a high activity for NBR latex hydrogenation without the use of any organic solvent. The influences of various operation conditions on hydrogenation rate, such as catalyst and polymer concentrations, latex system composition, agitation, reaction temperature and hydrogen pressure, have been investigated. It was found that the addition of triphenylphosphine (TPP) has a critical effect for the hydrogenation of NBR latex, and the hydrogenation rate was mainly controlled by the amount of catalyst which diffused into the polymer particles. In the presence of TPP, NBR latex can be hydrogenated to more than 95% degree of hydrogenation after about 30 hours at 160oC using Wilkinson’s catalyst with a catalyst to NBR rubber ratio of 1 wt%, without the addition of any organic solvent. The apparent activation energy for such NBR latex hydrogenation over the temperature range of 152oC to 170oC was found to be 57.0 kJ/mol. In the present study, it was also found that there are some impurities within the NBR latex which are detrimental to the hydrogenation reaction and are suspected to be water-soluble surfactant molecules. Deliberately designed solution hydrogenation experiments were conducted to study the impurity issue, and proper latex treatment methods have been found to purify the latex before hydrogenation. To improve the hydrogenation rate and to optimize the latex hydrogenation system, water soluble RhCl(TPPMS)3 catalyst (TPPMS: monosulphonated-triphenylphosphine) was used for the latex hydrogenation of NBR. The latex hydrogenation using the water soluble catalyst with TPP can achieve more than 90% degree of hydrogenation within 20 hours at 160oC. Further experiments using RhCl3 with TPP proved that the water soluble RhCl3 can be directly used as a catalyst precursor to generate the catalytic species in situ for the latex hydrogenation, and a stable NBR latex with 96% degree of hydrogenation can be produced without any gel problem within 19 hours of reaction at 160oC. The catalyst mass transport processes for these Rh based catalysts in the latex system were investigated in order to further optimize the solvent-free latex hydrogenation process. While maintaining the emulsified state of the original latex, the direct catalytic hydrogenation of NBR latex can be carried out efficiently without any cross-linking problem to more than 92% degree of hydrogenation within 8 hours at 160oC. As a result of this research project, new latex hydrogenation technologies were successfully developed to fulfill all major requirements for a solvent-free polymer latex hydrogenation route, which is a significant milestone for the improvement of this polymer modification technology. The finding of TPP’s role as the “catalyst mass transfer promoter” is a breakthrough for the research field related to the hydrogenation of unsaturated diene-based polymers in latex form.

The use of volatile organic compounds (VOC) in coating materials has adverse effects on both human health and the environment. Due to concern over these problems, coating industry has attempted to decrease the solvent contents of coating materials for the last three decades by developing water dispersed and powder paints. A recently developed method to make solvent free paint is to use highly branched polymers in high solid alkyd resins. Highly branched polymers help to achieve resins with viscosity much lower than its linear counterparts. In this study, a new alkyd based resin was formulated using long oil alkyd and melamine based hyperbranched polymer having 24 functional groups on its structure. The long oil alkyd was synthesized by using an oil mixture (40% linseed + 60% sunflower). Melamine was preferred as core molecule due to its excellent properties such as greater hardness, alkali and solvent resistance with thermal stability. The resin produced has low viscosity because its hyperbranched structure / therefore, it needs no solvent for its application. The chemical characterization of the resins with different compositions was performed using Fourier Transform Infrared Spectroscopy and thermal properties were determined by Differential Scanning Calorimetry. Physical and mechanical tests were conducted to determine hardness, flexibility, impact resistance, abrasion resistance, adhesion power, and gloss property of the samples. The viscosity of the resins decreased from 148 Pa.s to 8.84 Pa.s as the hyperbranched polymer to long oil alkyd ratio was increased from 1:3 to 1:24. On the other hand, the hardness values of the resins decreased from 198 Persoz to 43 Persoz. All resins showed excellent flexibility, formability, adhesion, and gloss.