ORCID Profile
0000-0002-5954-2694
Current Organisation
University of South Australia
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Publisher: Wiley
Date: 08-07-2020
DOI: 10.1002/JPPR.1631
Publisher: Wiley
Date: 06-09-2017
DOI: 10.1002/JPPR.1256
Publisher: Elsevier BV
Date: 03-1983
Publisher: Wiley
Date: 08-12-2012
Publisher: Oxford University Press (OUP)
Date: 03-2018
DOI: 10.2146/AJHP160457
Abstract: Results of a study to determine the stability of an extemporaneously compounded minoxidil oral suspension under various temperature and stress conditions are reported. Commercially available minoxidil tablets (10 mg) were crushed to a fine powder, and predetermined amounts of 2 suspending vehicles were added to produce a 1-mg/mL suspension, which was stored in glass bottles at room temperature (25 ± 2 °C) or in a refrigerator (4 ± 2 °C). To simulate daily patient use, 5 days weekly 1 bottle of the suspension was removed from refrigerated storage and shaken and 0.5 mL of the contents discarded. At each specified time point, s les were analyzed in duplicate ( The mean percentage of initial minoxidil concentration remaining in all refrigerated s les exceeded 90% throughout the 24-week study, with no change in appearance, pH, microbial activity, odor, or redispersibility. During storage at room temperature, the suspension exhibited a color change at week 4, with slight sedimentation after 6 weeks, although minoxidil recovery exceeded 90% for 10 weeks. An extemporaneously compounded minoxidil oral suspension was stable for 24 weeks when stored in a refrigerator. This suspension can be used for up to 3 weeks when stored at room temperature.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2020
Publisher: Wildlife Disease Association
Date: 07-2011
DOI: 10.7589/0090-3558-47.3.643
Abstract: Sarcoptic mange, caused by Sarcoptes scabiei var. wombati, could be a significant threat to populations of southern hairy-nosed wombats (Lasiorhinus latifrons SHNW) in Australia. Treatment is currently based on the off-label use of various parasiticidal drugs, with limited clinical efficacy trials. Our primary aim was to determine the pharmacokinetic parameters of a macrocyclic lactone, moxidectin, to assist in the development of effective treatment protocols. Pharmacokinetic parameters were determined in four female SHNW following a single subcutaneous injection of 0.2 mg/kg moxidectin. Blood s les were collected for 38 days following injection (August-September 2008), for analysis using liquid chromatography and tandem mass spectrometry. The mean peak plasma concentration occurred at 13.6 hr, with a mean peak plasma level of 98.6 ng/ml. The mean elimination half-life was 5.03 days, resulting in a mean area under the curve of 377 ng.day/ml. The peak plasma moxidectin concentration was higher than that seen in livestock species but the plasma elimination half-life was shorter. This study suggests that a single injection of 0.2 mg/kg moxidectin may not be sufficient to clear a mange infection in this species.
Publisher: Informa UK Limited
Date: 12-2011
DOI: 10.1080/10408398.2010.490883
Abstract: Colorectal cancer is the second leading cause of cancer death in Australia. Nutrition, particularly intake of vegetables and certain plant components, has been reported to have a major role in cancer risk reduction. Recently, there has been a growing research interest in rosemary, a common household plant grown in many parts of the world. This study aims to review scientific evidence from all studies, published from 1996 to March 2010 that examined the protective effects of rosemary on colorectal cancer and other types of cancer. Literature evidence from animal and cell culture studies demonstrates the anticancer potential of rosemary extract, carnosol, carnosic acid, ursolic acid, and rosmarinic acid. No evidence for other rosemary constituents was found. The reported anticancer properties were found to arise through the molecular changes in the multiple-stage process of cancer development, which are dose related and not tissue or species specific. This is evidenced by the ability of rosemary to suppress the development of tumors in several organs including the colon, breast, liver, stomach, as well as melanoma and leukemia cells. The results suggested that the different molecular targets modulated by rosemary and its active constituents are useful indicators of success in clinical cancer chemo-prevention trials.
Publisher: Bentham Science Publishers Ltd.
Date: 10-2007
DOI: 10.2174/157016307782109670
Abstract: Omeprazole (OME), a proton pump inhibitor used to treat acid reflux disease and gastric ulcers presents a formulation challenge due to its rapid decomposition at acidic and neutral pHs. Thus, the aim of this project was to investigate whether interaction with sulfobutylether-beta-cyclodextrin (Captisol-CD) could improve omeprazole stability and provide more efficient oral liquid formulations. A stability-indicating high performance liquid chromatography assay allowed for the quantitation of S- and R-forms of OME in the presence and absence of Captisol-CD. The developed method was validated to discriminate between OME and its degradation products and used to describe the kinetic model of OME at different pH values over a period of 36 days. Calculated degradation constants (k(obs)), were directly correlated with the H(+) concentrations of the solutions regardless of whether the omeprazole was complexed with the Captisol-CD or not. Moreover, the pH-rate profile curve indicated that in all cases, maximum stability was achieved at pH 11. Though it was anticipated that interaction of OME with Captisol-CD might increase the relative stability of OME at a lower pH, the cavity of the cyclodextrin was too small to allow the inclusion to occur. However the R-isomer of OME, both in the presence or absence of the cyclodextrin appeared to be slightly less stable than the corresponding S-form at the same pH conditions.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2020
Publisher: Therapeutic Guidelines Limited
Date: 02-1997
Publisher: Elsevier BV
Date: 09-1994
Publisher: Informa UK Limited
Date: 21-03-2011
DOI: 10.3109/03639045.2010.550300
Abstract: The aims of this study were to prepare and evaluate chitosan-polyacrylic acid complex (CS-PAA) as polymeric osmogents for swellable micro/nanoporous osmotic pump propranolol tablets. The complexes were characterized and evaluated for their swelling characteristics. The selected complexes were incorporated into the core propranolol tablets as polymeric osmogents. The core tablets were formulated, compressed as monolithic and two-layered tablets, and finally coated with cellulose acetate containing PEG 400 and PVP K30 as plasticizers and pore formers, respectively. As a final point, the drug release was determined. A direct correlation was found between the CS content in the complex and the maximum swelling force and swelling ratio of the complex mixture. In vitro drug release revealed that the percent drug release increased with the amount of osmogent in the two-layered tablets. Drug release could be prolonged up to 12h and conformed to the USP 31 criteria. In contrast, percent release decreased with the increasing amount of complexes in monolithic tablets. It was postulated that two opposing mechanisms were involved. Following water uptake, the complexes of polymers swelled and pushed the drug out of the tablets, and the drug bound to the polymer network and remained in the tablets. The results indicated that the complex of CS-PAA at optimal proportion and amount was a promising polymeric osmogent for a zero-order controlled release from two-layered swellable micro/nanoporous osmotic pump tablets.
Publisher: Wiley
Date: 14-09-2015
DOI: 10.1111/HEAD.12655
Abstract: Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache. To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids. Participants with MOH who were using opioids were randomized via computer-generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double-blind, parallel groups study. Before randomization participants completed a 4-week baseline headache diary. During treatment, headache diary data collection continued and participants attended 4 study visits during which quantitative sensory testing was performed. Blood s les for immune biomarker analyses were collected before and after treatment in a subgroup of participants. Thirty-four participants were randomized, 13 of 15 randomized to ibudilast and 17 of 19 randomized to placebo completed treatment. Ibudilast was generally well-tolerated with mild, transient nausea reported as the most common adverse event (66.7% vs 10.5% in placebo group). Results are shown as mean (SD). At the end of treatment no differences in the primary outcome average daily headache index (placebo 62 [44] vs ibudilast 77 [72] groups, difference -15, CI -65 to 35 h × numerical rating scale), or secondary outcomes headache frequency (placebo 23 [8.1] vs ibudilast 24.5 [6.2], difference -1.5, CI -7.7 to 4.8 days/month) and opioid intake (placebo 20.6 [43] vs ibudilast 19 [24.3], difference 1.6, CI -31.5 to 34.8 mg morphine equivalent) were observed between placebo and ibudilast groups. Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program.
Publisher: MDPI AG
Date: 11-06-2020
DOI: 10.3390/PH13060121
Abstract: Classified as a Biopharmaceutical Classification System (BCS) class IV drug, hotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB-loaded polymeric micelles (AmB-PM) to increase intestinal absorption. AmB-PM were prepared with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr®) method. AmB-PM have a mean particle size of ~80 nm and are mono-disperse with a polydispersity index .2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB-PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco-2 cells confirmed the safety/low toxicity of AmB-PM. In vitro cellular absorption studies confirmed that AmB-PM increased AmB uptake in Caco-2 cells 6-fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco-2 monolayers was significantly faster (2-fold) and more pronounced for AmB-PM in comparison to free drug (3.5-fold increase). Thus, the developed AmB-PM show promise as a novel oral delivery system for AmB and justifies further investigation.
Publisher: Public Library of Science (PLoS)
Date: 07-06-2012
Publisher: Wiley
Date: 10-2009
Publisher: American Chemical Society (ACS)
Date: 05-11-2012
DOI: 10.1021/PR3007107
Abstract: Butyrate and its analogues have long been investigated as potential chemotherapeutic agents. Our previous structure-activity relationship studies of butyrate analogues revealed that 4-benzoylbutyrate had comparable in vitro effects to butyrate when used to treat HT29 and HCT116 colorectal cancer cell lines. The aim of this study was to identify potential mechanisms associated with the antitumorigenic effects of 4-benzoylbutyrate. In this study, butyrate, 3-hydroxybutyrate and 4-benzoylbutyrate were also investigated for their effects on histone deacetylase (HDAC) activity and histone H4 acetylation in HT29 and HCT116 cells. The biological effects of these analogues on HT29 cells were further investigated using quantitative proteomics to determine the proteins potentially involved in their apoptotic and antiproliferative effects. Because 3-hydroxybutyrate had minimal to no effect on apoptosis, proliferation or HDAC activity, this analogue was used to identify differentially expressed proteins that were potentially specific to the apoptotic effects of butyrate and/or 4-benzoylbutyrate. Butyrate treatment inhibited HDAC activity and induced H4 acetylation. 4-Benzoylbutyrate inhibited HDAC activity but failed to enhance H4 acetylation. Proteomic analysis revealed 20 proteins whose levels were similarly altered by both butyrate and 4-benzoylbutyrate. Proteins that showed common patterns of differential regulation in the presence of either butyrate or 4-benzoylbutyrate included c-Myc transcriptional targets, proteins involved in ER homeostasis, signal transduction pathways and cell energy metabolism. Although an additional 23 proteins were altered by 4-benzoylbutyrate uniquely, further work is required to understand the mechanisms involved in its apoptotic effects.
Publisher: SAGE Publications
Date: 09-11-2012
Abstract: Patients with chronic headache who consume large amounts of analgesics are often encountered in clinical practice. Excessive intake of analgesics is now considered to be a cause, rather than simply a consequence, of frequent headaches, and as such the diagnosis “medication-overuse headache” (MOH) has been formulated. Despite the prevalence and clinical impact of MOH, the pathophysiology behind this disorder remains unclear and specific mechanism-based treatment options are lacking. Although most acute headache treatments have been alleged to cause MOH, here we conclude from the literature that opioids are a particularly problematic drug class consistently associated with worsening headache. MOH may not be a single entity, as each class of drug implicated may cause MOH via a different mechanism. Recent evidence indicates that chronic opioid administration may exacerbate pain in the long term by activating toll-like receptor-4 on glial cells, resulting in a pro-inflammatory state that manifests clinically as increased pain. Thus, from the available evidence it seems opioid-overuse headache is a phenomenon similar to opioid-induced hyperalgesia, which derives from a cumulative interaction between central sensitisation, due to repeated activation of nociceptive pathways by recurrent headaches, and pain facilitation due to glial activation. Treatment strategies directed at inhibiting glial activation may be of benefit alongside medication withdrawal in the management of MOH.
Publisher: Elsevier BV
Date: 10-2007
Abstract: Colorectal cancer (CRC) is the 3rd leading cause of cancer death in the United States and the 2nd leading cause of cancer death in Australia. Environmental factors play important roles in the multiple-stage process of CRC and nutritional intervention has been identified as playing a major role in its prevention. The aim of this study was to review systematically the scientific evidence from all studies conducted over the last decade that examined effects of garlic on CRC. Levels of evidence were ranked from level I to level V according to study designs and the quality of each study was assessed against a set of quality criteria based on those used by the National Health and Medical Research Council in Australia. One randomized controlled trial (RCT, level II) reported a statistically significant 29% reduction in both size and number of colon adenomas in CRC patients taking aged garlic extract. Five of 8 case control/cohort studies (level III) suggested a protective effect of high intake of raw/cooked garlic and 2 of 8 of these studies suggested a protective effect for distal colon. A published meta-analysis (level III) of 7 of these studies confirmed this inverse association, with a 30% reduction in relative risk. Eleven animal studies (level V) demonstrated a significant anticarcinogenic effect of garlic and/or its active constituents. On balance, there is consistent scientific evidence derived from RCT of animal studies reporting protective effects of garlic on CRC despite great heterogeneity of measures of intakes among human epidemiological studies.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.IJPHARM.2021.121382
Abstract: Cromoglycate is a mast cell stabiliser typically administered via inhalation or intranasally for the treatment of allergy-based respiratory issues. Oral dosing of cromoglycate remains challenging due to its high solubility but low permeability across epithelial membranes in the gastrointestinal tract: effective formulation strategies are clearly needed. Here, we investigate and preclinically develop chitosan-cromoglycate complexes and associated nano/microparticle formulations with muco-adhesive and permeation enhancing capabilities to overcome the biopharmaceutical challenges for oral dosing.The synthesized complexes were optimized with respect to chitosan grade, particle size, and drug loading and demonstrated up to a 9.3-fold enhancement in permeability across a Caco-2 monolayer for chitosan-cromoglycate particles, compared to the pure drug. This increased intestinal permeability led to improved pharmacokinetic performance of cromoglycate, e.g. up to 1.82-fold increase in relative oral bioavailability when dosed to Sprague-Dawley rats in a fasted state. These findings confirm the potential for chitosan particles to serve as an effective oral delivery vehicle for cromoglycate, with additional formulation optimization presenting the opportunity to reduce dosing frequency for treatment of allergy-based respiratory ailments.
Publisher: Informa UK Limited
Date: 12-1996
Publisher: Bentham Science Publishers Ltd.
Date: 07-2021
DOI: 10.2174/1871520620666200924104550
Abstract: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their antibreast cancer effects. The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peerreviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed that sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways that promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemo-resistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively lower inhibitory concentration IC 50 . The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane appeared to display the greatest potential.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BBI.2013.03.002
Abstract: Despite the wealth of evidence in animals that immune activation has a key role in the development and maintenance of chronic pain, evidence to support this in humans is scant. We have sought such evidence by examining the effect of a subtle immunological stimulus, low dose intravenous endotoxin, on the allodynia, hyperalgesia, flare and pain produced by intradermal capsaicin in healthy volunteers. Here we provide evidence of immune priming of this neuropathic-like pain response in humans. Specifically, in 12 healthy volunteers, activation of Toll-Like Receptor 4 by endotoxin (0.4ng/kg IV) caused significant 5.1-fold increase in the 90-min integral of areas of capsaicin-induced allodynia (95% CI 1.3-9.1), 2.2-fold increase in flare (95% CI 1.9-2.6) and 1.8-fold increase in hyperalgesia (95% CI 1.1-2.5) following 50μg intradermal capsaicin injected into the forearm 3.5h after endotoxin. These data demonstrate clinically a significant role for the neuroimmune pain connection in modifying pain, thus providing evidence that immune priming may produce pain enhancement in humans and hence offer a novel range of pharmacological targets for anti-allodynics and/or analgesics. Additionally, the simplicity of the model makes it suitable as a test-bed for novel immune-targeted pain therapeutics.
Publisher: Wiley
Date: 06-2007
DOI: 10.1002/J.2055-2335.2007.TB00026.X
Abstract: Although warfarin is a commonly prescribed oral anticoagulant, published data on the stability of mixtures prepared from warfarin tablets are limited. To investigate the stability of mixtures formulated using Coumadin tablets, Marevan tablets or warfarin sodium clathrate. A stability indicating high performance liquid chromatography (HPLC) method was developed to determine the concentration of warfarin. Warfarin sodium clathrate was forcibly degraded and injected into the HPLC system to ascertain lack of interference from degradation product peaks from the warfarin peak. Warfarin mixtures (1 mg/mL) were prepared in triplicate from Coumadin tablets, Marevan tablets and warfarin sodium clathrate using compound hydroxybenzoate solution APF as a preservative. A four‐level calibration was used. On each study day each s le was injected into the HPLC system in duplicate together with quality control standards and blanks. Warfarin concentrations were calculated from the linear regression equation derived from the calibration curve. The method was stability indicating as the degradation peaks did not interfere with the principal peak and UV spectral confirmation was used to identify the warfarin peak. All mixtures retained at least 98% of their original concentration over the 28‐day study period. Warfarin mixtures can be formulated by either suspending crushed tablets or preparing a solution from warfarin sodium clathrate. Compound hydroxybenzoate solution APF can be used as the preservative. A 28‐day shelf‐life can be assigned to the products.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Publisher: Wiley
Date: 12-2017
DOI: 10.1002/JPPR.1404
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.EJPB.2016.11.034
Abstract: This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe redict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated "mechanism-based" models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability.
Publisher: Springer Science and Business Media LLC
Date: 07-12-2022
Publisher: Wiley
Date: 12-2009
DOI: 10.1897/08-587.1
Abstract: Pharmaceuticals released into aquatic systems are expected to sorb to sediments to varying degrees. Their sorption is likely to influence their fate and, ultimately, the risk they pose to aquatic organisms. This has led to the European Medicines Agency requiring an assessment of affinity to solids, using batch sorption methods, for the environmental risk assessment (ERA) of new human medicines. However, a large body of data is generated before pharmaceuticals are released onto the market, including their extent of distribution throughout the human body, measured by the volume of distribution (VD). In the present study, batch sorption experiments were undertaken using 12 different soils and sediments to determine whether VD was a good indicator of experimental Kd values for 21 pharmaceuticals. The r2 values obtained from the regressions ranged from 0.39 to 0.76 (with a median value of 0.5) and all regressions were found to be significant. The use of this more comprehensive set of soils and sediments was consistent with previous studies comparing VD and Kd, despite the Kd values of the selected pharmaceuticals varying greatly between soils. The relationship between Kd and VD was greatly improved when zwitterionic antibiotics and carbamazepine were not included, possibly due to complex sorption or pharmacokinetic behavior. There are likely to be a number of factors affecting the sorption of pharmaceuticals that cannot be explained by VD. However, further work may elucidate how these factors can be accounted for, enabling VD to be effectively used to facilitate the ERA of human pharmaceuticals with already available information.
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.CHEMOSPHERE.2006.05.036
Abstract: The recognition of pharmaceuticals as significant environmental contaminants has only been a recent phenomenon. Therefore there is a paucity of data relating to the fate and effects of pharmaceuticals once they enter an aquatic receiving system. The amount of work that needs to be done in terms of risk assessment for pharmaceuticals required by regulatory agencies is substantial. This paper has determined the environmental partitioning coefficient (K(d)) of 13 erse human pharmaceuticals in three model systems of differing combinations of solid phases and solutions. The K(d) values were then compared with distribution values of the pharmaceuticals in the human body determined from pharmacological studies. This was done to assess the functional relationship between K(d) and distribution values in the human body (V(D)). K(d) values ranged from 3 to 2450 L kg(-1). Regression coefficients ranged from r(2)=0.62-0.72, indicating that V(D) values are a useful indicator for the K(d) values of the tested pharmaceuticals within the batch sorption systems. The relationship between K(d) and V(D) should therefore be further explored to determine whether this relationship can be applied to a broader range of pharmaceuticals in more erse environmental systems. Exploiting available human pharmacological data in such a way would be of great benefit in prioritising human pharmaceuticals as environmental contaminants in the risk assessment process.
Publisher: Wiley
Date: 03-1990
Abstract: A three-way crossover study was performed to compare the bioavailability of a new pelletised doxycycline product administered either with food or without food and a reference product taken without food. Four different methods were used to calculate pharmacokinetic parameters from the data. The sums of squares, Akaike's Information Criterion (AIC), and the ranges for the parameters obtained were used for comparison. Good fits to the data were obtained when all four methods were used, each with a lag time. The two compartment open model was the most efficient method for describing the data. The one compartment open model was the least efficient, particularly with respect to predicting the peak concentration of doxycycline in plasma. All the models gave similar rank order results with respect to bioavailability differences between the three treatments. Analysis of the data by different methods suggests that pelletised doxycycline is bioequivalent to the reference product when taken in the absence of food. A standardized feeding regimen affected the rate, but not extent of absorption of doxycycline from the pelletised formulation.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.IJPHARM.2022.122424
Abstract: Warming of the skin is now an accepted means of promoting skin permeation. Accordingly, the usually quite onerous thermodynamic studies on solute transport through the skin have practical applications. Phenolic compounds permeate through the skin by partitioning into and diffusing through the stratum corneum (SC) intercellular lipids, with their size being the main determinant of their maximal solute flux through skin. This paper sought to characterise the enthalpic and entropic changes associated with the solubility and equilibrium partitioning into the human SC of a series of phenols similar in size but with differing log P from aqueous vehicles. The solubilities of 9 phenolic compounds, covering a range of polarities, were determined in water and SC following 72 h at 4, 24, 32 and 37°C which allowed the estimation of the SC-water partition coefficients. Van't Hoff plots were then used to estimate the enthalpies and entropies for the SC solubility, water solubility and SC partitioning of phenols. In addition, partition coefficients of 3 of the 9 phenols from mineral oil into hydrated and dehydrated SC were measured at the same temperatures. Van't Hoff plots were then used to estimate the enthalpies and entropies for the SC solubility, water solubility and SC partitioning of phenols from the oil. The SC solubility for the polar phenols increased more with temperature than the non-polar phenols, with the SC-water partition coefficients increasing with temperature for the polar phenols but decreasing with temperature for the non-polar phenols. Thermodynamic analyses suggest that, while enthalpy and entropy effects are involved in the SC partitioning of the non-polar solutes, the SC partitioning of the polar phenols were almost entirely entropy driven. The resultant thermodynamic parameters are consistent with the polar phenols being mainly associated with the SC polar head groups whereas the nonpolar phenols were more likely to be located in the interior interface SC lipid region adjacent to the polar head groups. Further, hydrating the SC led to an increase in the enthalpy of partitioning for both the polar and non-polar phenols studied. The estimated entropy of the partitioning for solutes from dehydrated SC suggests this is not only a hydrophobic effect in water but that the partitioning arises from the nature of phenolic compound - SC intercellular lipid interactions and SC intercellular lipid entropy. This partitioning process is dominated more by the extent of interaction between the SC and solute than the hydrophobic effect in water and is likely to be even greater above the SC lipid phase transition at around 36
Publisher: Elsevier BV
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 25-05-2010
Publisher: MDPI AG
Date: 07-12-2020
Abstract: Despite being one of the first-line treatments for osteoporosis, the bisphosphonate drug class exhibits an extremely low oral bioavailability ( %) due to poor absorption from the gastrointestinal tract. To overcome this, and to explore the potential for sustained drug release, bioerodible poly(lactic acid) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) implants loaded with the bisphosphonate alendronate sodium (ALN) were prepared via hot-melt extrusion. The rate of drug release in vitro was modulated by tailoring the ratio of lactide to glycolide in the polymer and by altering the ALN-loading of the implants. All investigated implants exhibited sustained ALN release in vitro between 25 to 130 days, where implants of greater glycolide composition and higher ALN-loadings released ALN more rapidly. All PLGA implants demonstrated a sigmoidal release profile, characterised by an initial surface dissolution phase, followed by a period of zero-order drug diffusion, then relaxation or erosion of the polymer chains that caused accelerated release over the subsequent days. Contrastingly, the PLA implants demonstrated a logarithmic release profile, characterised by a gradual decrease in ALN release over time.
Publisher: Elsevier BV
Date: 2023
Publisher: Future Medicine Ltd
Date: 06-2021
Abstract: Although statins are effective in treating high cholesterol, adverse effects do occur with their use. Efficacy and tolerability vary among statins in different ethnic groups. Indigenous Australians have a high risk for cardiovascular and kidney diseases. Prescribing statins to Indigenous Australians with multi-morbidity requires different strategies to increase efficacy and reduce their toxicity. Previous studies have reported that Indigenous Australians are more susceptible to severe statin-induced myopathies. However, there is a lack of evidence in the underlying genetic factors in this population. This review aims to identify: inter-ethnic differences in the efficacy and safety of statins major contributing factors accounting for any identified differences and provide an overview of statin-induced adverse effects in Indigenous Australians.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.IJPHARM.2022.121695
Abstract: The concomitant administration of oral drugs with food can result in significant changes in bioavailability, leading to variable pharmacokinetics and considerable clinical implications, such as over- or under-dosing. Consequently, there is increasing demand for bio-enabling formulation strategies to reduce variability in exposure between the fasted and fed state and/or mitigate the pharmaceutical food effect. The current review critically evaluates technologies that have been implemented to overcome the positive food effects of pharmaceutical drugs, including, lipid-based formulations, nanosized drug preparations, cyclodextrins, amorphisation and solid dispersions, prodrugs and salts. Additionally, improved insight into preclinical models for predicting the food effect is provided. Despite the wealth of research, this review demonstrates that application of optimal formulation strategies to mitigate the positive food effects and the evaluation in preclinical models is not a universal approach, and improved standardisation of models to predict the food effects would be desirable. Ultimately, the successful reformulation of specific drugs to eliminate the food effect provides a panoply of advantages for patients with regard to clinical efficacy and compliance.
Publisher: Wiley
Date: 03-1990
Abstract: Eighteen healthy, non-smoking, adult volunteers participated in single and multiple dose three-way crossover studies to evaluate a sustained-release, pellet-filled capsule of theophylline, Austyn. The effect of food on the bioavailability of the sustained-release capsule was investigated by administering 300 mg single doses of Austyn, with a high-fat meal and without food and a ided 300 mg dose of the reference product Elixophyllin elixir, given after fasting. Plasma theophylline concentrations were measured by fluorescence polarization immunoassay (FPIA) which had been validated against HPLC. The single dose study data showed that there were no significant differences (n = 18, ANOVA, p greater than 0.05) between the three regimens with respect to AUC0-infinity values (mg h l-1), (mean +/- SD) Elixophyllin fasting = 97.1 +/- 33.7, Austyn with food = 90.9 +/- 31.3, Austyn fasting = 91.2 +/- 33.8. Similarly, multiple dosing with rapid-release Nuelin tablets, Austyn capsules, and sustained-release Theo-Dur tablets demonstrated that there were no significant differences between regimens with respect to AUC0-24h, AUC0-12h, and AUC12-24h values calculated from the steady-state concentrations (5th day, 24 h s ling). However, the percentage fluctuation at steady-state over the total blood s ling period was significantly less for treatment with the sustained-release capsule. Austyn, compared with the sustained-release tablet, Theo-Dur (Austyn = 36.7 +/- 13.7 per cent, Theo-Dur = 53.1 +/- 14.1 per cent). The results of the single and multiple dose studies indicate that Austyn capsules demonstrate complete bioavailability, and good controlled release characteristics not influenced by concomitant intake of a high-fat meal and with no evidence of dose dumping.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2014
DOI: 10.1038/TP.2014.121
Publisher: Springer Science and Business Media LLC
Date: 03-04-2021
No related grants have been discovered for Desmond Williams.