3 resultados para Tartaric acid.
em Aston University Research Archive
Resumo:
The purpose of this investigation was to study the dissolution behavior of paracetamol and ibuprofen in the presence of a range of selected potential excipients. First, a pH-solubility profile was generated for both drugs, and the effect of changing hydrodynamic conditions on the intrinsic dissolution rate was investigated. It was established that both drugs dissolved according to the diffusion-layer model. Paracetamol solubility (approximately 20.3 mg mL -1) did not vary from pH 1.2-8.0, corresponding to the in vivo range in the gastrointestinal tract. Ibuprofen had an intrinsic solubility of approximately 0.06 mg mL-1, and pKa was calculated as 4.4. Second, the effects of selected potential excipients (lactose, potassium bicarbonate, sodium bicarbonate, sodium chloride, and tartaric acid) were evaluated by measuring the effect of the inclusion of each additive in the dissolution medium on drug solubility, drug intrinsic dissolution rate, and solution viscosity. The results were evaluated using the diffusion-layer model, and it was determined that for paracetamol, the collected data fitted the model for all the excipients studied. For ibuprofen, it was found that there were differences between the excipients that raised the solution pH above the pK a to those that did not. For the excipients raising the pH above the pKa, the effect on intrinsic dissolution rate was not as high as that expected from the change in drug solubility. It was postulated that this might be due to lack of penetration of the excipient into the drug boundary layer microenvironment. Formulators may calculate the effect of adding an excipient based on solubility increases but may not find the dissolution rate improvement expected. Copyright © 2005 Taylor & Francis Inc.
Resumo:
A study is reported on the deactivation of hydroprocessing catalysts and their reactivation by the removal of coke and metal foulants. The literature on hydrotreating catalyst deactivation by coke and metals deposition, the environmental problems associated with spent catalyst disposal, and its reactivation/rejuvenation process were reviewed. Experimental studies on catalyst deactivation involved problem analysis in industrial hydroprocessing operations, through characterization of the spent catalyst, and laboratory coking studies. A comparison was made between the characteristics of spent catalysts from fixed bed and ebullating bed residue hydroprocessing reactor units and the catalyst deactivation pattern in both types of reactor systems was examined. In the laboratory the nature of initial coke deposited on the catalyst surface and its role on catalyst deactivation were studied. The influence of initial coke on catalyst surface area and porosity was significant. Both catalyst acidity and feedstock quality had a remarkable influence on the amount and the nature of the initial coke. The hydroenitrogenation function (HDN) of the catalyst was found to be deactivated more rapidly by the initial coke than the hydrodesulphurization function (HDS). In decoking experiments, special attention was paid to the initial conditions of coke combustion, since the early stages of contact between the coke on the spent catalyst surface and the oxygen are crucial in the decoking process. An increase in initial combustion temperature above 440oC and the oxygen content of the regeneration gas above 5% vanadium led to considerable sintering of the catalyst. At temperatures above 700oC there was a substantial loss of molybdenum from the catalyst, and phase transformations in the alumina support. The preferred leaching route (coked vs decoked form of spent catalyst) and a comparison of different reagents (i.e., oxalic acid and tartaric acid) and promoters (i.e., Hydrogen Peroxide and Ferric Nitrate) for better selectivity in removing the major foulant (vanadium), characterization and performance evaluation of the treated catalysts and modelling of the leaching process were addressed in spent catalyst rejuvenation studies. The surface area and pore volume increased substantially with increasing vanadium extraction from the spent catalyst; the HDS activity showed a parallel increase. The selectivity for leaching of vanadium deposits was better, and activity recovery was higher, for catalyst rejuvenated by metal leaching prior to decoking.
Resumo:
Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.