Beverley Glass

Titanium dioxide photocatalysis for pharmaceutical wastewater treatment

Heterogeneous photocatalysis using the semiconductor titanium dioxide (TiO2) has proven to be a promising treatment technology for water purification. The effectiveness of this oxidation technology for the destruction of pharmaceuticals has also been demonstrated in numerous studies. This review highlights recent research on TiO2 photocatalytic treatment applied to the removal of selected pharmaceuticals. The discussions are tailored based on the therapeutic drug classes as the kinetics and mechanistic aspects are compound dependent. These classes of pharmaceuticals were chosen because of their environmental prevalence and potential adverse effects. Optimal operational conditions and degradation pathways vary with different pharmaceutical compounds. The main conclusion is that the use of TiO2 photocatalysis can be considered a state-of-the-art pharmaceutical wastewater treatment methodology. Further studies are, however, required to optimize the operating conditions for maximum degradation of multiple pharmaceuticals in wastewater under realistic conditions and on an industrial scale.

The identification of the UV degradants of melatonin and their ability to scavenge free radicals

Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2–· and particularly the ·OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC‐MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2–· generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400‐W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC‐MS results show that the degradants of melatonin are 6‐hydroxymelatonin and N1‐acetyl‐N2‐formyl‐5‐methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)‐induced superoxide generation compared to non‐irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.

The thermal and photostability of solid pharmaceuticals

Drugs degrade to different extents on separate exposure to heat, moisture, oxidation and light. Combination of these stresses causes very complex behaviour. Many studies have been reported of the thermal behaviour of drugs in the solid-state, but most of the information available on the photodegradation of drugs refers to reactions in solution, (usually aqueous) and photoreactions in the solid-state are even more complex. In drug formulations, the presence of excipients adds further complications because the excipients may increase, have no effect on, or decrease the inherent stabilities of the drug. The literature has been explored to review the thermal and photostabilities of solid pharmaceuticals.

Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity.

Oxidative damage of biological macromolecules is a hallmark of most neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body diseases. Another important phenomenon involved in these disorders is the alteration of iron homeostasis, with an increase in iron levels. The present study investigated whether 6‐hydroxymelatonin (6‐OHM) can reduce Fe2+‐induced lipid peroxidation and necrotic cell damage in the rat hippocampus in vivo. It was found that 6‐OHM administration proved successful in reducing Fe2+‐induced neurotoxicity in rat hippocampus. This study provides some evidence of the neuroprotective effects of 6‐OHM.

TiO2 photocatalysis of naproxen: effect of the water matrix, anions and diclofenac on degradation rates.

The TiO2 photocatalytic degradation of the active pharmaceutical ingredient (API) naproxen (NPX) has been studied using a laboratory-scale photoreactor equipped with a medium pressure mercury lamp. UV/TiO2 photocatalysis proved highly efficient in the elimination of NPX from a variety of water matrices, including distilled water, unfiltered river water and drinking water, although the rate of reaction was not always proportional to TiO2 concentration. However, the NPX degradation rate, which follows first-order kinetics, was appreciably reduced in river water spiked with phosphate and chloride ions, a dual anion system. Addition of chloride into drinking water enhanced the TiO2-photocatalysed degradation rate. Competitive degradation studies also revealed that the NPX degradation was greatly reduced in the presence of increased concentrations of another API, diclofenac (DCF). This was established by (i) the extent of mineralization, as determined by dissolved organic carbon (DOC) content, and (ii) the formation of intermediate NPX by-products, identified using liquid chromatography and electrospray ionization (positive and negative mode) mass spectrometry techniques. This study demonstrates that competition for active sites (anions or DCF) and formation of multiple photoproducts resulting from synergistic interactions (between both APIs) are key to the TiO2-photocatalysed NPX degradation.

Analysing the crystal purity of mebendazole raw material and its stability in a suspension formulation.

The objective of this study was to develop a simple, direct and non-destructive method to assess crystal purity of mebendazole raw material and to establish its stability in a suspension formulation using diffuse reflectance ultraviolet (DRA-UV) spectroscopy and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Quantitation of mebendazole, found to exhibit polymorphism with three polymorphic forms A, B and C identified, was carried out with ATR-FTIR spectroscopy. Artificial neural network (ANN) was employed as a data-modelling tool. The developed ANN models confirmed that the characteristic absorptions in the infrared (IR) spectral region are directly proportional to the measured amounts of mebendazole crystal forms present in the samples (r(2)>0.94), which was confirmed with X-ray diffraction (XRD) at r(2)>0.97. These models also predicted that the mebendazole raw material contained 7.21+/-1.25% (ATR-FTIR data) and 10.38+/-0.18% (XRD data) of form A as an impurity. ATR-FTIR data for the suspension formulation showed some dissolution of form C and recrystalisation as the more stable form A. These quantitative results obtained for the binary crystal form mixtures clearly demonstrate the strong potential of ATR-FTIR for use in the determination of the polymorphic content not only in bulk pharmaceuticals but also in liquid formulations.

Prediction of a Stable Microemulsion Formulation for the Oral Delivery of a Combination of Antitubercular Drugs Using ANN Methodology

AbstractPurpose. The aim of this project was to develop a colloidal dosage form for the oral delivery of rifampicin and isoniazid in combination with the aid of artificial neural network (ANN) data modeling. Methods. Data from the 20 pseudoternary phase triangles containing miglyol 812 as the oil component and a mixture of surfactants or a surfactant/cosurfactant blend were used to train, test, and validate the ANN model. The weight ratios of individual components were correlated with the observed phase behavior using radial basis function (RBF) network architecture. The criterion for judging the best model was the percentage success of the model prediction. Results. The best model successfully predicted the microemulsion region as well as the coarse emulsion region but failed to predict the multiphase liquid crystalline phase for cosurfactant-free systems indicating the difference in microemulsion behavior on dilution with water. Conclusions. A novel microemulsion formulation capable of delivering rifampicin and isoniazid in combination was created to allow for their differences in solubility and potential for chemical reaction. The developed model allowed better understanding of the process of microemulsion formation and stability within pseudoternary colloidal systems.

6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates

Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol-indophenol as an electron acceptor. The results of this study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.

Stability Implications of Repackaging Paracetamol Tablets into Dose Administration Aids

Despite the widespread use of dose administration aids (DAAs) there is little available data on the stability of drugs during repackaging or storage in these devices.

Pharmaceutical applications of the Prout-Tompkins rate equation

More than 50 years ago, a paper by E.G. Prout and F.C. Tompkins was published in the Transactions of the Faraday Society. The paper dealt with the kinetics of the thermal decomposition of crystals of potassium permanganate, and suggested a rate equation, which has become known as the Prout-Tompkins equation, for use in the kinetic analysis of solid state reactions. The paper has been extensively cited in the literature. Applications of the Prout-Tompkins equation in pharmaceutical stability studies are reviewed in this short review.