Research Institute in Healthcare Science

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A qualitative mixed-method narrative study on psychotherapeutic support needs based on a series of 11 cases of survivors of the 2023 Odisha train accident
(Springer Nature, 2025-03-25) Swain, Sarada P.; Behura, Sushree S.; Banerjee, Shraddha; Mahakul, Sukanya; Kar, Nilamadhab; Research Institute in Healthcare Science, Faculty of Science and Engineering
Background: Rail and road accidents are common in India and are extremely stressful life events. Many accident survivors develop stress-related mental health problems but do not get psychotherapeutic support. We intended to analyse the needs and types of techniques for the psychotherapeutic support of the survivors of the 2023 train accident in Odisha and to reflect on how the services can be facilitated. Methods: It was a qualitative, mixed-method, narrative study based on the interview of a sample of 11 survivors of the train accident. Results: It was observed that the survivors and their families had many unresolved psychological issues related to the trauma of the train accident and its consequences. The survivors articulated their mental health concerns holistically in a comprehensive way. It appeared that their psychotherapeutic needs were unmet. Examples of psychological interventions needed were psychoeducation, relaxation, supportive and cognitive therapies, and specific trauma-focused cognitive behavioural therapy. Many challenges in providing psychotherapies were identified, such as limited awareness about the need for psychotherapeutic intervention, affected persons in geographically highly dispersed areas, unavailability of psychotherapeutic services or personnel in most places, and lack of resources. Conclusion: The train accident survivors have immense psychotherapeutic needs, but these are mostly unmet. Modifying the provision methods to tele-psychotherapy and training other healthcare personnel such as nurses, and counsellors might help the resource-scarce situation.
Challenges in managing depression in clinical practice: result of a global survey
(MDPI, 2025-02-18) Kar, Nilamadhab
Background/Objectives: Despite an improved knowledgebase, effective intervention, and guidelines, many patients with depression do not receive adequate treatment and treatment discontinuation and non-response are common. It was intended to explore the challenges clinicians face while managing depression in their clinical practice and their suggestions for solutions. Methods: It was an online survey of 137 psychiatrists in 18 countries including both high and low economies, using a pre-designed questionnaire; with both quantitative and qualitative measures. Results: Antidepressant prescribing appeared close to the evidence-based guidelines. There was frequent use of other medications alongside antidepressants since treatment initiation. There were many challenges in managing depression, such as treatment non-response, resistance, and discontinuation; side effects, mostly sexual problems; inadequate psychological intervention; availability and affordability of treatment modalities; comorbidities, especially substance use and personality disorders; stigma; and lack of education and training. Suggested approaches for solutions included personalized treatment, quicker follow-up, psychoeducation, blending psychological intervention into routine clinical practice, improving continuity of care, and preventing treatment discontinuation. Support from governments for improving access, making interventions affordable, and providing socio-occupational support is essential. Training and development of professionals, public education providing information, and dealing with stigma are still relevant. Conclusions: The results indicated a need for reviewing current practices in managing depression, optimizing it with available resources, and preventing treatment discontinuation, and non-response. Making treatment available and affordable, public education fighting stigma to improve treatment acceptability, and research addressing gaps in interventions, especially for treatment resistance and psychotherapy are other approaches that may improve depression management.
Identifying gaps in congenital CMV detection—implications for the recent European Consensus guidelines on congenital CMV infection
(Wiley, 2024-11-14) Elhefnawy, Nahed; Frain, Isobel; Currie, Andrew; Kairamkonda, Venkatesh; Cusack, Jonathan; Fawke, Joe; Bandi, Srini; Siddiqui, Farah; Dunkerton, Suzanna; Kelf, Stefan; Barker, Tammy; Bird, Paul W.; Holmes, Christopher W.; Toovey, Oliver T.R.; Pillay, Thillagavathie; Tang, Julian W.
Explainable artificial intelligence in paediatrics: challenges for the future
(Wiley, 2024-12-12) Salih, Ahmed M.; Menegaz, Gloria; Pillay, Thillagavathie; Boyle, Elaine M.
Background Explainable artificial intelligence (XAI) emerged to improve the transparency of machine learning models and increase understanding of how models make actions and decisions. It helps to present complex models in a more digestible form from a human perspective. However, XAI is still in the development stage and must be used carefully in sensitive domains including paediatrics, where misuse might have adverse consequences. Objective This commentary paper discusses concerns and challenges related to implementation and interpretation of XAI methods, with the aim of rising awareness of the main concerns regarding their adoption in paediatrics. Methods A comprehensive literature review was undertaken to explore the challenges of adopting XAI in paediatrics. Results Although XAI has several favorable outcomes, its implementation in paediatrics is prone to challenges including generalizability, trustworthiness, causality and intervention, and XAI evaluation. Conclusion Paediatrics is a very sensitive domain where consequences of misinterpreting AI outcomes might be very significant. XAI should be adopted carefully with focus on evaluating the outcomes primarily by including paediatricians in the loop, enriching the pipeline by injecting domain knowledge promoting a cross-fertilization perspective aiming at filling the gaps still preventing its adoption.
Framing stress and associated behaviours at work: an ethnography study in the United Kingdom
(Emerald Publishing Group, 2019-11-18) Hampton, Paul; Chinyio, Ezekiel; Riva, Silvia
Aim: The purpose is to understand more precisely the culture and interpersonal behaviours associated with stress. Methods: The research was conducted using a qualitative approach through an ethnographic methodology in relation to three companies. The greater part of the data collection period was structured into observations that ranged between 2 and 4 hours per day, 1 to 3 days per week, for a period of 6 months. A total of 10 sites were explored; and on each site, the observations involved activities by 5 to 20 people. Findings: The results showed the pivotal importance of interpersonal relationships in coping with the uncertainty of working conditions, the coordination of team-work, and managing responsibilities and power interactions. It was found that the impact of stress is multifaceted, affecting the physical status, interpersonal relationships, work performance, and emotional wellbeing of construction workers. The workers who were studied emphasised five sources of support that help moderate work-related stress: additional tools such as communication systems and software, a facilitated access to professional help (e.g. psychological services), organisational changes in leadership, provision of resources for the wellbeing of personnel (e.g. job training) and better teamwork. Practical implications: The study underlines the importance of dedicated services for stress management and specific training-related abilities devoted to reinforcing positive person-organization dynamics. In particular, the abilities should relate to managing the impact of stress in terms of physique, interpersonal relationships, work performance, and emotional well-being. Originality/value: This is one of the first studies to adopt a psychological perspective for understanding construction scenarios and phenomena and was conducted by a qualified psychologist.
Antidiabetic activities of chloroform fraction of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes
(Elsevier, 2018-10-18) Anyanwu, Gabriel O.; Iqbal, Jamshed; Khan, Shafi U.; Zaib, Sumera; Rauf, Khalid; Onyeneke, Chukwu E.; Ojo, Opeolu
ETHNOPHARMACOLOGICAL RELEVANCE: Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus. AIM OF THE STUDY: To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes. MATERIALS AND METHODS: Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150 mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination. RESULTS: LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92 µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97 µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200 mg/kg CF significantly improved glucose tolerance (P < 0.001) and enhanced serum insulin levels (P < 0.05) compared to diabetic control rats. CONCLUSIONS: Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action.
Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone
(Wiley, 2018-12-27) Ali, Naser M.; Niada, Stefania; Brini, Anna T.; Morris, Mark R.; Kurusamy, Sathishkumar; Alholle, Abdullah; Huen, David; Antonescu, Cristina R.; Tirode, Franck; Sumathi, Vaiyapuri; Latif, Farida
Undifferentiated pleomorphic sarcoma of bone (UPSb), is a rare primary bone sarcoma that lacks a specific line of differentiation. There is very little information about the genetic alterations leading to tumourigenesis or malignant transformation. Distinguishing between UPSb and other malignant bone sarcomas, including dedifferentiated chondrosarcoma and osteosarcoma, can be challenging due to overlapping features. To explore the genomic and transcriptomic landscape of UPSb tumours, whole-exome sequencing (WES) and RNA Sequencing (RNA-Seq) were performed on UPSb tumours. All tumours lacked hotspot mutations in IDH1/2 132 or 172 codons, thereby excluding the diagnosis of dedifferentiated chondrosarcoma. Recurrent somatic mutations in TP53 were identified in 4/14 samples (29%). Moreover, recurrent mutations in histone chromatin remodelling genes, including H3F3A, ATRX and DOT1L, were identified in 5/14 samples (36%), highlighting the potential role of deregulated chromatin remodelling pathways in UPSb tumourigenesis. The majority of recurrent mutations in chromatin remodelling genes identified here are reported in COSMIC, including the H3F3A G35 and K36 hotspot residues. Copy number alteration analysis identified gains and losses in genes that have been previously altered in UPSb or UPS of soft tissue. Eight somatic gene fusions were identified by RNA-Seq, two of which, CLTC-VMP1 and FARP1-STK24, were reported previously in multiple cancers. Five gene fusions were genomically characterised. Hierarchical clustering analysis, using RNA-Seq data, distinctly clustered UPSb tumours from osteosarcoma and other sarcomas, thus molecularly distinguishing UPSb from other sarcomas. RNA-Seq expression profiling analysis and quantitative RT-PCR showed an elevated expression in FGF23 which can be a potential molecular biomarker in UPSb. To our knowledge, this study represents the first comprehensive WES and RNA-Seq analysis of UPSb tumours revealing novel protein-coding recurrent gene mutations, gene fusions and identifying a potential UPSb molecular biomarker, thereby broadening the understanding of the pathogenic mechanisms and highlighting the possibility of developing novel targeted therapeutics.
Towards identifying potent new hits for glioblastoma
(Royal Society of Chemistry, 2018-10-02) Sherer, Chris; Prabhu, Saurabh; Adams, David; Hayes, Joseph; Rowther, Farzana; Tolaymat, Ibrahim; Warr, Tracy; Snape, Timothy J.
Glioblastoma is a devastating disease of the brain and is the most common malignant primary brain tumour in adults. The prognosis for patients is very poor with median time of survival after diagnosis measured in months, due in part to the tumours being highly aggressive and often resistant to chemotherapies. Alongside the ongoing research to identify key factors involved in tumour progression in glioblastoma, medicinal chemistry approaches must also be used in order to rapidly establish new and better treatments for brain tumour patients. Using a computational similarity search of the ZINC database, alongside traditional analogue design by medicinal chemistry intuition to improve the breadth of chemical space under consideration, six new hit compounds (14, 16, 18, 19, 20 and 22) were identified possessing low micromolar activity against both established cell lines (U87MG and U251MG) and patient-derived cell cultures (IN1472, IN1528 and IN1760). Each of these scaffolds provides a new platform for future development of a new therapy in this area, with particular promise shown against glioblastoma subtypes that are resistant to conventional chemotherapeutic agents.
Insights into the molecular mechanisms of action of bioportides: a strategy to target protein-protein interactions
(2015-01-27) Howl, John; Jones, Sarah
Protein Mimicry and the Design of Bioactive Cell-Penetrating Peptides
(2015) Howl, John; Jones, Sarah
The multi-domain architecture of many human proteins provides a structural basis for the physical maintenance of interactomes, or networks of protein-protein interactions (PPIs), that are so obviously crucial to cellular functions. Moreover, the structural and electrostatic complementarity provided by PPI interfaces, predominantly located on protein surfaces, is a fundamental component of signal transduction events that are known to be compromised in human diseases including many cancers.The pharmacokinetic advantages provided by cell-penetrating peptides (CPPs) are entirely compatible with the development of intrinsically permeable agents capable of modulating intracellular PPIs. Thus, the term bioportide is a useful descriptor of numerous bioactive CPPs that are distinct from the more usual inert CPP vectors. Herein we illustrate a generic strategy, predominantly centered upon the identification of cationic peptides derived from helical protein domains, which offers a reliable platform to identify bioportides capable of modulating intracellular signal transduction events. In addition, we describe robust methodologies to determine the precise intracellular distribution of fluorescent bioportides and present assays routinely employed to screen for the detrimental pharmacodynamic properties often exhibited by both CPPs and bioportides; namely adverse cytotoxicity and the receptor-independent stimulation of mast cell secretion.
Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells
(2015-02-07) Howl, John; Jones, Sarah
Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors
(2016-03-17) Lahart, Ian; Metsios, George S.; Nevill, Alan M.; Kitas, George D.; Carmichael, Amtul R.
Background: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. Methods: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. Results: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk−1, p = .024, 382.2 MET-min∙wk−1, p = .010, and 264.1 MET-min∙wk−1, p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, −1.6 kg, p = .040, and −.6 kg/m2, p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p= .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p=.007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, −.38 mmol∙L−1, p=.001; and −.3 mmol∙L−1, p=.023, respectively). Conclusions: We found that home-based PA resulted in significant albeit small to moderate improvements in selfreported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care.
Germline Mutations in the CDKN2B Tumor Suppressor Gene Predispose to Renal Cell Carcinoma.
(American Association for Cancer Research, 2015-04-14) Jafri, Mariam; Wake, Naomi C; Ascher, David B; Pires, Douglas E V; Gentle, Dean; Morris, Mark R.; Rattenberry, Eleanor; Simpson, Michael A; Trembath, Richard C; Weber, Astrid; Woodward, Emma R; Donaldson, Alan; Blundell, Tom L; Latif, Farida; Maher, Eamonn R
Familial renal cell carcinoma (RCC) is genetically heterogeneous and may be caused by mutations in multiple genes, including VHL, MET, SDHB, FH, FLCN, PTEN, and BAP1. However, most individuals with inherited RCC do not have a detectable germline mutation. To identify novel inherited RCC genes, we undertook exome resequencing studies in a familial RCC kindred and identified a CDKN2B nonsense mutation that segregated with familial RCC status. Targeted resequencing of CDKN2B in individuals (n = 82) with features of inherited RCC then revealed three candidate CDKN2B missense mutations (p.Pro40Thr, p.Ala23Glu, and p.Asp86Asn). In silico analysis of the three-dimensional structures indicated that each missense substitution was likely pathogenic through reduced stability of the mutant or reduced affinity for cyclin-dependent kinases 4 and 6, and in vitro studies demonstrated that each of the mutations impaired CDKN2B-induced suppression of proliferation in an RCC cell line. These findings identify germline CDKN2B mutations as a novel cause of familial RCC.
A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells
(Public Library of Science (United States), 2016-04-28) Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco
The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems.
Ionically Crosslinked Chitosan Hydrogels for the Controlled Release of Antimicrobial Essential Oils and Metal Ions for Wound Management Applications
(MDPI AG, Basel, Switzerland, 2016-03-01) Kenward, M.A.; Amin, Mohd; Martin, Claire; Low, Wan Li
The emerging problems posed by antibiotic resistance complicate the treatment regime required for wound infections and are driving the need to develop more effective methods of wound management. There is growing interest in the use of alternative, broad spectrum, pre-antibiotic antimicrobial agents such as essential oils (e.g., tea tree oil, TTO) and metal ions (e.g., silver, Ag+). Both TTO and Ag+ have broad spectrum antimicrobial activity and act on multiple target sites, hence reducing the likelihood of developing resistance. Combining such agents with responsive, controlled release delivery systems such as hydrogels may enhance microbiocidal activity and promote wound healing. The advantages of using chitosan to formulate the hydrogels include its biocompatible, mucoadhesive and controlled release properties. In this study, hydrogels loaded with TTO and Ag+ exhibited antimicrobial activity against P. aeruginosa, S. aureus and C. albicans. Combining TTO and Ag+ into the hydrogel further improved antimicrobial activity by lowering the effective concentrations required, respectively. This has obvious advantages for reducing the potential toxic effects on the healthy tissues surrounding the wound. These studies highlight the feasibility of delivering lower effective concentrations of antimicrobial agents such as TTO and Ag+ in ionically crosslinked chitosan hydrogels to treat common wound-infecting pathogens.
Thermal energy storage using metal–organic framework materials
(Applied Energy, 2016-04-05) Elsayed, Ahmed; Elsayed, Eman; Al-Dadah, Raya; Mahmoud, Saad; Elshaer, Amr; Kaialy, Waseem
Metal–organic framework (MOF) materials are new adsorbent materials that have high surface area and pore volume and hence high adsorption uptake. The previous exceptional properties make this class of materials have a great potential in many applications like cooling, gas separation and energy storage. However, there is very limited information on the performance of metal–organic framework materials in energy storage applications and their performance compared to conventional adsorbents. This paper aims to present an experimental characterisation of CPO-27(Ni) MOF material for water adsorption and to investigate its viability for energy storage. CPO-27(Ni) (known as MOF-74(Ni)), which is a MOF material that has high water adsorption capabilities of 0.47 gH2O gads−1 and hydrothermally stable and can be supplied in large quantities. Firstly, the material water adsorption isotherms were predicated using Materials Studio software via the material structure information and then compared to the experimentally measured isotherms. The experimentally measured isotherms and kinetics were used to model a double bed adsorption system for energy storage application using Simulink–Matlab software coupled with Nist RefProp thermophysical routines. Finally, the performance of CPO-27(Ni) was then compared with silica gel. The CPO-27(Ni) was found to outperform silica gel at long half cycle time (more than 30 min) at low evaporating temperature making it suitable for energy storage applications. The energy stored in the condenser and the adsorption bed was found to be dependent mostly on the regeneration and the cooling temperatures. The potential of the energy recovered from the adsorption bed can be double the one recovered from the condenser. Also, the energy recovery during condensation and adsorption was found to be independent of the reactor conductance except at small conductance ratio. Finally, the adsorption unit cooling water flow strategy was found to affect the amount of the energy recovered as recirculating the cooling water through the adsorption bed and then condenser was found to decrease the recovered energy from the condenser by 4%.
Recent advances in the engineering of nanosized active pharmaceutical ingredients: Promises and challenges
(Elsevier BV, 2015-12-08) Kaialy, Waseem; Al Shafiee, Maen
The advances in the field of nanotechnology have revolutionized the field of delivery of poorly soluble active pharmaceutical ingredients (APIs). Nanosized formulations have been extensively investigated to achieve a rapid dissolution and therefore pharmacokinetic properties similar to those observed in solutions. The present review outlines the recent advances, promises and challenges of the engineering nanosized APIs. The principles, merits, demerits and applications of the current ‘bottom-up’ and ‘top-down’ technologies by which the state of the art nanosized APIs can be produced were described. Although the number of research reports on the nanoparticle engineering topic has been growing in the last decade, the challenge is to take numerous research outcomes and convert them into strategies for the development of marketable products.
A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets
(Elsevier, 2015-08-29) ElShaer, Amr; Kaialy, Waseem; Akhtar, Noreen; Iyire, Affiong; Hussain, Tariq; Alany, Raid; Mohammed, Afzal R.
The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y = 28.01 MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (r) increased from 0.2 ± 0.05 N/mm2 to 2.85 ± 0.36 N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets’ disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (r) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets.
The use of freeze-dried mannitol to enhance the in vitro aerosolization behaviour of budesonide from the Aerolizer®
(Elsevier B.V., 2015-11-14) Kaialy, Waseem; Nokhodchi, Ali
The efficiency of drug delivery from drug-carrier dry powder inhaler (DPI) systems is typically low. The purpose of this study was to examine the aerosolization performance of a hydrophobic drug, budesonide (BUD), from DPI formulations containing a promising carrier, freeze-dried mannitol (FDM), and to compare the results to those obtained previously with a hydrophilic drug, salbutamol sulphate (SS). The results showed that, in comparison to the formulation containing commercial BUD and commercial lactose, a total of 3.8-fold increase in the fine particle fraction (FPF) was obtained from the formulation containing FDM (FPF: 7.5% versus 29%) whereas a total of 4.6-fold increase in the FPF was obtained from the formulation containing FDM and leucine additive (FPF: 35%). Regression analysis showed DPI formulations containing carrier particles with a more elongated/less spherical shape, a higher content of fine particulates (< 5 μm) and a higher porosity to produce higher FPFs of BUD. FDM promoted the aerosolization of budesonide intended for pulmonary delivery. The addition of leucine (by 4.8%, w/w) has further improved the flow and the aerosolization properties of FDM. FDM produced higher aerodynamic diameters and smaller FPFs of BUD as compared to SS, attributable to BUD having a higher electrostatic charge density and a higher agglomeration tendency than SS.
Characterisation and in vitro antimicrobial potential of liposome encapsulated silver ions against Candida albicans
(Taylor & Francis, 2016-01-20) Kenward, M A; Hill, D J; Martin, C; Low, Wan Li
Liposomes are biocompatible, biodegradable, controlled delivery systems with the ability to encapsulate both lipophilic and hydrophilic compounds, including metal ions. Liposome encapsulated Ag(+) (lipo-Ag(+)), prepared by reverse-phase evaporation, was used as a controlled delivery system against Candida albicans. Characterisation of the lipo-Ag(+) indicated that the multilamellar vesicles with diameters ranging between ≈ 0.5 and 5.0 μm showed potential as a controlled delivery system to consistently deliver Ag(+) to C. albicans. Results from inductively coupled plasma (ICP) analysis showed higher association of cell bound Ag(+) at 15 mins post exposure when compared to unencapsulated Ag(+). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate detrimental effects of Ag(+) on C. albicans cell structure. These effects along with the ICP results also correlate with previously reported time kill experiment observations.

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