No / Crystallisation is a widely used technique for purification and manipulation of the final crystal form of therapeutic agents. In particular, potential exists to control the mechanical properties of ibuprofen through control of crystal habit. The aim of this study was therefore to understand the influence of crystallisation conditions on the morphology of ibuprofen to enable production of crystals with different habits.

Thesis (M.S.)--University of Florida, 2006. / Typescript. Title from title page of source document. Document formatted into pages; contains 34 pages. Includes Vita. Includes bibliographical references.

Thesis (M.S.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 31 pages. Includes Vita. Includes bibliographical references.

No description available.

A dissertation submitted to the Faculty of Dentist University of the Witwatersrand, Johannesburg, in part fulfilment of the requirements for the degree of Master Dentistry in the Branch of Maxillo-Facial and Oral Surgery. / Pain, swelling and trismus are common features after oral surgery, particularly after the surgical removal of impacted third molar teeth. The Maxillo-Facial and Oral Surgeon has a vast array of drugs at his disposal to combat post-operative pain, but none of these are perfect in terms of efficacy and side effects. Recently, the non-steroidal anti-inflammatory drugs have been receiving much attention as post-operative analgesics. / IT2018

It is a well reported fact that large number of drugs coming of the drug discovery pipeline show poor aqueous solubility. Eutectic mixture formation of poorly soluble drugs with hydrophilic carriers has been used to enhance the dissolution rate of such poorly soluble drugs. Eutectic mixtures are solid dispersions where the drug and the carrier are both in crystalline form. The eutectic mixture has a lower melting point than either component. Eutectic mixtures are thermodynamically stable systems. The feasibility of developing a dosage form from an eutectic mixture depends on the phase diagram. Poloxamers are polyoxyethylene-polyoxypropylene-polyoxyethylene block polymers which have surfactant properties. Phase diagram construction and dissolution rate enhancement mechanism in crystalline poloxamer based eutectics has not been reported in pharmaceutical literature. This thesis involved the detailed study of poloxamer 188 (PL 188) based eutectic mixtures. Eutectic mixture formation between PL 188 and drugs with diverse physicochemical properties was proved. Accurate experimental phase diagrams were constructed using solid state characterization techniques and theoretical phase diagrams were predicted using Lacoulonche et al's model. The model was accurate in predicting the phase diagrams of most drugs. Discrepancies were observed in case of drugs showing hydrogen bonding interactions with PL 188. This was confirmed by a blue shift of the carbonyl band using fourier transform infra-red spectroscopy. A unique novel graphical method for estimating the accurate eutectic composition of PL 188 based eutectics with about 50 mg of drug was devised. PL 188 was effective in improving the dissolution rate of a poorly soluble drug ibuprofen in pH 1, 4.5 and 7.2. For the first time a detailed study establishing melting point depression due to eutectic formation as a reason for dissolution enhancement was described. Contrary to expectation it was realized that maximum dissolution rate enhancement takes place at drug ratios well above the eutectic composition. The utility of PL 188 as a eutectic mixture carrier was shown by comparing ketoprofen PL 188 eutectic mixtures with ketoprofen soluplus (glass solutions) and ketoprofen urea solid dispersions(amorphous precipitation in crystalline carrier). The ketoprofen PL 188 eutectic mixtures had better dissolution enhancing effect and physical stability. / Pharmaceutical Sciences

The presence of human pharmaceuticals in the environment has raised concerns regarding their potential adverse effects on non-target aquatic organisms. Pharmaceuticals are designed to target specific molecular pathways in humans in order to produce known pharmacological and physiological responses, before toxicological effects are seen. The “Read-Across Hypothesis” stipulates that pharmaceuticals can produce similar biological effects in fish, as in humans, if the molecular target is conserved, and the internal (blood plasma) concentrations are similar. The read-across hypothesis was tested using ibuprofen, a non-steroidal anti-inflammatory drug, and the model fish test species, the fathead minnow (Pimephales promelas), to determine if ibuprofen can cause similar target-mediated effects in teleost fish and humans, at comparable blood plasma concentrations. Fathead minnows were exposed, using continuous flow-through systems, for ≤96 hours to a range of ibuprofen water concentrations (100, 270, 370 and 500 µg/L) to determine if plasma concentrations similar to human therapeutic plasma concentrations (HTPCs, or Cmax) could be established in fish blood plasma. The mode of action of ibuprofen was used to identify relevant endpoints (i.e. cyclooxygenase (COX) enzyme) in order to examine target-mediated effects following drug exposure. The water and plasma ibuprofen concentrations were determined using LC-MS/MS. The measured ibuprofen plasma concentrations in individual fish were linked to target-mediated effects on COX gene expression, COX enzyme activity and prostaglandin E2 (PGE2) synthesis (products of COX activity), which were quantified using molecular (QPCR) and biochemical (colourimetric and enzyme immunoassay) assays, and linked with the Cmax of ibuprofen. It was demonstrated that in fish with a mean ibuprofen plasma concentration 1.8-fold below the Cmax, PGE2 concentrations (the most robust endpoint) was significantly inhibited following ibuprofen exposure. However, in fish exposed to an ibuprofen concentration closer to (2 to 3-fold above) environmentally relevant water concentrations (i.e. 9 µg/L), when the mean plasma concentration was 224-fold below the Cmax, fish did not respond to ibuprofen exposure. This study provides qualitative and quantitative evidence for the applicability of the “read-across hypothesis”, and highlights its potential utility for prioritising pharmaceuticals for environmental risk assessment.

O ibuprofeno é um anti-inflamatório não-esteroidal (AINE) que possui propriedades analgésicas e anti-térmicas e é empregado na terapêutica em casos dores discretas e moderadas, artrite reumatóide, osteoartrite e dismenorréia primária, nas concentrações de 200, 300, 400 e 600 mg. Entretanto, a formulação contendo 200 mg não está disponível no mercado farmacêutico brasileiro. No presente trabalho, foi desenvolvida uma formulação de comprimidos de ibuprofeno 200 mg que apresentou, além de outras características físico-químicas adequadas, um ótimo perfil de dissolução. Foram testadas oito formulações, obtidas a partir de um projeto fatorial fracionado, avaliando-se diversos excipientes. Além disto, as formulações foram submetidas à temperatura ambiente, 37 ºC e 50 ºC, e analisadas à 30 e 60 dias, com o objetivo de avaliar as transformações físicas que podem ocorrer durante o armazenamento das mesmas. Os resultados das análises físico-químicas foram tratados estatisticamente, utilizando-se o programa STATGRAFCS, através de uma análise exploratória e de um estudo de efeitos. Concluiu-se, então, que a melhor formulação foi a seguinte: IBUPROFENO - 200; AMIDO - 47; LACTOSE - 72; CELULOSE MICROCRISTALINA - 23; ESTEARATO DE MAGNESIO - 8. / Ibuprofen is a non steroidal antiinflamatory drug (NSAD), that has analgesic and antipyretic properties. It is used in terapeutic cases of mild to moderant pain, rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea, in the 200, 300, 400, and 600 mg of concentration. In the Brazilian pharmaceutical market the formulation of 200 mg doesn\'t exist. In this study, a formulation of ibuprofen was developed for 200 mg tablets, that has suitable physical-chemical properties and an excellent dissolution profile. The eight formulations tested were obtained from factorial designs, evaluating several excipients. These formulations also had been submitted at room temperature, 37 ºC, and 50 ºC and were analised at 30 and 60 days, with the objective to evaluate the physical transformatiom that could have occurred during that time. The results were tested statistically by the STATGRAFCS program, using the exploratory analysis and the effects study. The final results showed that the best formulation was: IBUPROFEN - 200; STARCH - 47; LACTOSE - 72; MICROCRYSTALLINE CELLULOSE - 23; MAGNESIUM STEARATE - 8.

Pharmaceuticals are a group of emerging organic compounds of environmental concern used extensively in human and veterinary medicine. They are continually released into the environment as a result of manufacturing operations and excretion from humans and animals. These compounds enter directly into the municipal sewage systems and into wastewater treatment plants. A large number of important and potentially harmful organic contaminants, such as these pharmaceuticals, are not regulated in drinking and other waters. As a result, conventional technologies at most waste water treatment plants (WWTPs) discharge water that meet regulatory standards, yet are not specifically designed to remove these organic contaminants. Therefore, pharmaceutical compounds and their metabolites remain in discharged effluent and enter into the natural aquatic environment. Concentrations of pharmaceutical residues measured in water are typically reported in the ranges of ug/L to ng/L, which are at least three to four orders of magnitude lower than that required to produce a pharmacological effect. The probability of risks to humans arising from such an acute exposure is unlikely, but the possible effects resulting from life-long exposures and synergistic effects from exposure to many chemicals have yet to be determined. It has been widely reported that pharmaceuticals and their metabolites that enter into the aquatic environment can have a potential harmful effect on the aquatic ecosystem and can reach drinking water sources. This research focuses on non-steroid anti-inflammatory drugs (NSAIDs), a group of pharmaceuticals which are widely used as analgesic, antipyretic and anti-inflammatory agents. NSAIDs are frequently used because they are easily accessible as over the counter medication and are a group of drugs that do not produce addiction, respiratory depression, or drowsiness. There is an incentive for removing NSAIDs and other pharmaceuticals from the aquatic environment. Thus, quantitative evaluation of the fate of pharmaceuticals, proper risk assessment and improvement of the efficiency of WWTPs need sensitive and reliable analytical methods. The purpose of this project was to provide a method for detecting three common NSAIDs, IBF, KTF, and NAP, in purified water with LLE-GC-FID. And, an investigation of UV photolysis, UV/H2O2, and UV/TiO2 AOPs was performed to determine their effectiveness in treating IBF, KTF, and NAP in purified water. All treatment methods were successful in degrading target compounds with a total degradation of 86% or greater after 45 minutes. A liquid-liquid extraction technique using methylene chloride and BSTFA + 1%TMCS derivatizing agent was determined for detecting low concentrations of IBF, KTF, and NAP with calibration curves showing good linearity with all R2 values greater than 0.9880.

A quitosana tem se mostrado muito atrativa para a indústria farmacêutica, visando principalmente matrizes de liberação controlada com fármacos amplamente utilizados pela população em altas dosagens ou em períodos prolongada tal como o Ibuprofeno. O uso de combinado de polímeros e materiais como a argila é uma opção interessante, unindo as propriedades de ambos os materiais, minimizando o efeito colateral do fármaco. No presente trabalho descreve-se a preparação de um complexo iônico contendo quitosana e ibuprofeno por meio de uma reação ácido base entre ambos. Em uma segunda etapa, foi preparado um nanocompósito de montmorilonita/quitosana contendo o fármaco ibuprofeno. As matrizes foram caracterizadas por diferentes técnicas, incluindo análise elementar, ressonância magnética nuclear (RMN) de 13C e 1H, termogravimetria (TG), calorimetria exploratória diferencial (DSC), difração de raios X (DRX) e espectroscopia de infravermelho com transformada de Fourrier (FTIR). O grau de desacetilação (GD) da quitosana obtido por titulação potenciométrica foi de 80,0%. Esses resultados foram confirmados por medidas de RMN 1H e RMN 13C. O estudo dissociação do fármaco, na presença e na ausência de argila, foi avaliado por cromatografia líquida de alta eficiência (CLAE) e por espectroscopia de absorção eletrônica UV-VIS. A dissociação do fármaco em meio aquoso foi avaliada em pH 2 e 7, que correspondem aos valores encontrados no estômago e no intestino, respectivamente. Os resultados indicaram que a dissociação do ibuprofeno das matrizes é dependente do pH e que a presença da argila retarda a dissociação do fármaco na matriz. / Due to its interesting properties chitosan has attracted interest regarding several applications including drug carrier in pharmaceutical industry, mainly for actives consumed in high doses for long periods, as Ibuprofen. The combined use of materials such as polymers and the clay is an interesting option, combining the properties of both materials while minimizing the side effects of the drug. A chitosan-ibuprofen ionic complex had been prepared from the acid-base reaction between both of them. In a second step a montmorilonite/chitosan nanocomposite containing ibuprofen was also prepared. The complex and the nacomposite containing ibuprofen had been characterized by several techniques including elemental analysis, 13C e 1H, nuclear magnetic resonance (NMR), thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourrier transform infrared spectroscopy (FTIR). The chitosan degree of deacetylation (DD) was determined by potentiometry as 80.0%. These results were confirmed by 13C e 1H NMR. The dissociation of the pharmaceutical from the complex and nanocomposite was investigated by high performance liquid chromatography (HPLC) and electronic spectroscopy in the UV-vis (UV-vis). The dissociation of the pharmaceutical from the complex in aqueous media was evaluated in pH 2 and 7, corresponding to the stomach and intestines respectively. Results revealed that such dissociation is dependent of the pH of the medium as well as that release of Ibuprofen from the matrices is dependent on the pH and the presence of the clay slows the dissociation of the drug from the matrix.