Assessment of Dissolution Profile of Marketed Aceclofenac Formulations

Statistical comparison of dissolution profiles under a variety of conditions relating to formulation characteristics, lot-to-lot, and brand-to-brand variation attracts interest of pharmaceutical scientist. The objective of this work is to apply several profile comparison approaches to the dissolution data of five-marketed aceclofenac tablet formulations. Model-independent approaches including ANOVA-based procedures, ratio test procedure, and pair wise procedure. The ratio test includes percentage, area under the curve, mean dissolution time, while the pair wise procedure includes difference factor (f1), similarity factor (f2), and Rescigno index. In the model-dependent approach, zero order, first order, Hixson-Crowell, Higuchi, and Weibull models were applied to the utilization of fit factors. All the approaches were applicable and useful. ANOVA with multiple comparison tests was found to be sensitive and discriminating for comparing the profiles. Weibull parameters were more sensitive to the difference between two release kinetic data in terms of curve shape and level

Aquatic food security:insights into challenges and solutions from an analysis of interactions between fisheries, aquaculture, food safety, human health, fish and human welfare, economy and environment

Fisheries and aquaculture production, imports, exports and equitability of distribution determine the supply of aquatic food to people. Aquatic food security is achieved when a food supply is sufficient, safe, sustainable, shockproof and sound: sufficient, to meet needs and preferences of people; safe, to provide nutritional benefit while posing minimal health risks; sustainable, to provide food now and for future generations; shock-proof, to provide resilience to shocks in production systems and supply chains; and sound, to meet legal and ethical standards for welfare of animals, people and environment. Here, we present an integrated assessment of these elements of the aquatic food system in the United Kingdom, a system linked to dynamic global networks of producers, processors and markets. Our assessment addresses sufficiency of supply from aquaculture, fisheries and trade; safety of supply given biological, chemical and radiation hazards; social, economic and environmental sustainability of production systems and supply chains; system resilience to social, economic and environmental shocks; welfare of fish, people and environment; and the authenticity of food. Conventionally, these aspects of the food system are not assessed collectively, so information supporting our assessment is widely dispersed. Our assessment reveals trade-offs and challenges in the food system that are easily overlooked in sectoral analyses of fisheries, aquaculture, health, medicine, human and fish welfare, safety and environment. We highlight potential benefits of an integrated, systematic and ongoing process to assess security of the aquatic food system and to predict impacts of social, economic and environmental change on food supply and demand

Oestradiol-releasing Biodegradable Mesh Stimulates Collagen Production and Angiogenesis: An Approach to Improving Biomaterial Integration in Pelvic Floor Repair

Background Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed. Objective To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation. Design, setting, and participants Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments. Intervention The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays. Outcome measurements and statistical analysis Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer. Results and limitations The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p = 0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p = 0.001). Further studies in longer-term animal models are required to confirm these results. Conclusions Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation. Patient summary In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients’ tissues and merit further study in physiologically relevant animal models

Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion related to the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)

<p>Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver a scientific opinion on the Tolerable Upper Intake Level (UL) of the n-3 LCPUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). Available data are insufficient to establish a UL for n-3 LCPUFA (individually or combined) for any population group. At observed intake levels, consumption of n-3 LCPUFA has not been associated with adverse effects in healthy children or adults. Long-term supplemental intakes of EPA and DHA combined up to about 5 g/day do not appear to increase the risk of spontaneous bleeding episodes or bleeding complications, or affect glucose homeostasis immune function or lipid peroxidation, provided the oxidative stability of the n-3 LCPUFAs is guaranteed. Supplemental intakes of EPA and DHA combined at doses of 2 6 g/day, and of DHA at doses of 2 4 g/day, induce an increase in LDL-cholesterol concentrations of about 3 % which may not have an adverse effect on cardiovascular disease risk, whereas EPA at doses up to 4 g/day has no significant effect on LDL cholesterol. Supplemental intakes of EPA and DHA combined at doses up to 5 g/day, and supplemental intakes of EPA alone up to 1.8 g/day, do not raise safety concerns for adults. Dietary recommendations for EPA and DHA based on cardiovascular risk considerations for European adults are between 250 and 500 mg/day. Supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. No data are available for DPA when consumed alone. In the majority of the human studies considered, fish oils, also containing DPA in generally unknown (but relatively low) amounts, were the source of EPA and DHA.</p&gt

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). Funding: The National Institute for Health Research Health Technology Assessment programme