The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs

Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could be used to create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayer forming, whilst asymmetric lipids formed less condensed monolayers. However this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency.

The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs

Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. © 2012 Elsevier B.V. All rights reserved.

A critical evaluation of the volume, relevance and quality of evidence submitted by the tobacco industry to oppose standardised packaging of tobacco products

OBJECTIVES: To examine the volume, relevance and quality of transnational tobacco corporations' (TTCs) evidence that standardised packaging of tobacco products 'won't work', following the UK government's decision to 'wait and see' until further evidence is available. DESIGN: Content analysis. SETTING: We analysed the evidence cited in submissions by the UK's four largest TTCs to the UK Department of Health consultation on standardised packaging in 2012. OUTCOME MEASURES: The volume, relevance (subject matter) and quality (as measured by independence from industry and peer-review) of evidence cited by TTCs was compared with evidence from a systematic review of standardised packaging . Fisher's exact test was used to assess differences in the quality of TTC and systematic review evidence. 100% of the data were second-coded to validate the findings: 94.7% intercoder reliability; all differences were resolved. RESULTS: 77/143 pieces of TTC-cited evidence were used to promote their claim that standardised packaging 'won't work'. Of these, just 17/77 addressed standardised packaging: 14 were industry connected and none were published in peer-reviewed journals. Comparison of TTC and systematic review evidence on standardised packaging showed that the industry evidence was of significantly lower quality in terms of tobacco industry connections and peer-review (p<0.0001). The most relevant TTC evidence (on standardised packaging or packaging generally, n=26) was of significantly lower quality (p<0.0001) than the least relevant (on other topics, n=51). Across the dataset, TTC-connected evidence was significantly less likely to be published in a peer-reviewed journal (p=0.0045). CONCLUSIONS: With few exceptions, evidence cited by TTCs to promote their claim that standardised packaging 'won't work' lacks either policy relevance or key indicators of quality. Policymakers could use these three criteria-subject matter, independence and peer-review status-to critically assess evidence submitted to them by corporate interests via Better Regulation processes.

International trade law, plain packaging and tobacco industry political activity:the Trans-Pacific Partnership

Tobacco companies are increasingly turning to trade and investment agreements to challenge measures aimed at reducing tobacco use. This study examines their efforts to influence the Trans-Pacific Partnership (TPP), a major trade and investment agreement which may eventually cover 40% of the world's population; focusing on how these efforts might enhance the industry's power to challenge the introduction of plain packaging. Specifically, the paper discusses the implications for public health regulation of Philip Morris International's interest in using the TPP to: shape the bureaucratic structures and decision-making processes of business regulation at the national level; introduce a higher standard of protection for trademarks than is currently provided under the Agreement on Trade Related Aspects of Intellectual Property Rights; and expand the coverage of Investor-State Dispute Settlement which empowers corporations to litigate directly against governments where they are deemed to be in breach of investment agreements. The large number of countries involved in the TPP underlines its risk to the development of tobacco regulation globally.

Catalytic supercritical water gasification of plastics with supported RuO2:a potential solution to hydrocarbons-water pollution problem

Here we report on a potential catalytic process for efficient clean-up of plastic pollution in waters, such as the Great Pacific Garbage Patch (CPGP). Detailed catalytic mechanisms of RuO2 during supercritical water gasification of common polyolefin plastics including low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP) and polystyrene (PP), have been investigated in a batch reactor at 450 °C, 60 min. All four plastics gave very high carbon gasification efficiencies (CGE) and hydrogen gasification efficiencies (HGE). Methane was the highest gas component, with a yield of up to 37 mol kg−1LDPE using the 20 wt% RuO2 catalyst. Evaluation of the gas yields, CGE and HGE revealed that the conversion of PS involved thermal degradation, steam reforming and methanation; whereas hydrogenolysis was a possible additional mechanism during the conversion of aliphatic plastics. The process has the benefits of producing a clean-pressurized methane-rich fuel gas as well as cleaning up hydrocarbons-polluted waters.

Short cycle times for cost-efficient processing in lyophilized formulations

Pharmaceutical scientists who bulk freeze dry need to foremost identify what quality factors are of a priority during cycle development since the economics of freeze-drying do not allow for both the cost-efficient production and the ability to obtain the highest quality score across all quality factors. Consider; morphology, activity, dissolution, long-term storage, packaging and cost.

In situ diagnostics and prognostics of wire bonding faults in IGBT modules for electric vehicle drives

This paper presents a diagnostic and prognostic condition monitoring method for insulated-gate bipolar transistor (IGBT) power modules for use primarily in electric vehicle applications. The wire-bond-related failure, one of the most commonly observed packaging failures, is investigated by analytical and experimental methods using the on-state voltage drop as a failure indicator. A sophisticated test bench is developed to generate and apply the required current/power pulses to the device under test. The proposed method is capable of detecting small changes in the failure indicators of the IGBTs and freewheeling diodes and its effectiveness is validated experimentally. The novelty of the work lies in the accurate online testing capacity for diagnostics and prognostics of the power module with a focus on the wire bonding faults, by injecting external currents into the power unit during the idle time. Test results show that the IGBT may sustain a loss of half the bond wires before the impending fault becomes catastrophic. The measurement circuitry can be embedded in the IGBT drive circuits and the measurements can be performed in situ when the electric vehicle stops in stop-and-go, red light traffic conditions, or during routine servicing.

Optical fiber sensors embedded in flexible polymer foils

In traditional electrical sensing applications, multiplexing and interconnecting the different sensing elements is a major challenge. Recently, many optical alternatives have been investigated including optical fiber sensors of which the sensing elements consist of fiber Bragg gratings. Different sensing points can be integrated in one optical fiber solving the interconnection problem and avoiding any electromagnetical interference (EMI). Many new sensing applications also require flexible or stretchable sensing foils which can be attached to or wrapped around irregularly shaped objects such as robot fingers and car bumpers or which can even be applied in biomedical applications where a sensor is fixed on a human body. The use of these optical sensors however always implies the use of a light-source, detectors and electronic circuitry to be coupled and integrated with these sensors. The coupling of these fibers with these light sources and detectors is a critical packaging problem and as it is well-known the costs for packaging, especially with optoelectronic components and fiber alignment issues are huge. The end goal of this embedded sensor is to create a flexible optical sensor integrated with (opto)electronic modules and control circuitry. To obtain this flexibility, one can embed the optical sensors and the driving optoelectronics in a stretchable polymer host material. In this article different embedding techniques for optical fiber sensors are described and characterized. Initial tests based on standard manufacturing processes such as molding and laser structuring are reported as well as a more advanced embedding technique based on soft lithography processing.

Standardised tobacco packaging:a health policy case study of corporate conflict expansion and adaptation

Objectives: To investigate opposition to standardised tobacco packaging in the UK. To increase understanding of how transnational corporations are adapting to changes in their access to policymakers precipitated by Article 5.3 of the Framework Convention on Tobacco Control (FCTC). Design: Case study web-based documentary analysis, using NVivo V.10. Examination of relationships between opponents of standardised packaging and transnational tobacco companies (TTCs) and of the volume, nature, transparency and timing of their activities. Setting: UK standardised packaging policy debate 2011-2013. Participants: Organisations selected on basis of opposition to, or facilitation thereof, standardised tobacco packaging in the UK; 422 associated documents. Results: Excluding tobacco manufacturing and packaging companies (n=12), 109 organisations were involved in opposing standardised packaging, 82 (75%) of which had a financial relationship with 1 or more TTC. These 82 organisations (43 actively opposing the measure, 39 facilitating opposition) were responsible for 60% of the 404 activities identified, including the majority of public communications and research production. TTCs were directly responsible for 28% of total activities, predominantly direct lobbying, but also financially underwrote third party research, communication, mass recruitment and lobbying. Active organisations rarely reported any financial relationship with TTCs when undertaking opposition activities. Conclusions: The multifaceted opposition to standardised packaging was primarily undertaken by third parties with financial relationships with major tobacco manufacturers. Low levels of transparency regarding these links created a misleading impression of diverse and widespread opposition. Countries should strengthen implementation of Article 5.3 of the FCTC by systematically requiring conflict of interest declarations from all organisations participating in political or media debates on tobacco control.

A retrospective study examining the nature, contributory factors and predictors of dispensing errors in community pharmacy

Introduction: Since 2005, the workload of community pharmacists in England has increased with a concomitant increase in stress and work pressure. However, it is unclear how these factors are impacting on the ability of community pharmacists to ensure accuracy during the dispensing process. This research seeks to extend our understanding of the nature, outcome, and predictors of dispensing errors. Methodology: A retrospective analysis of a purposive sample of incident report forms (IRFs) from the database of a pharmacist indemnity insurance provider was conducted. Data collected included; type of error, degree of harm caused, pharmacy and pharmacist demographics, and possible contributory factors. Results: In total, 339 files from UK community pharmacies were retrieved from the database. The files dated from June 2006 to November 2011. Incorrect item (45.1%, n = 153/339) followed by incorrect strength (24.5%, n = 83/339) were the most common forms of error. Almost half (41.6%, n = 147/339) of the patients suffered some form of harm ranging from minor harm (26.7%, n = 87/339) to death (0.3%, n = 1/339). Insufficient staff (51.6%, n = 175/339), similar packaging (40.7%, n = 138/339) and the pharmacy being busier than normal (39.5%, n = 134/339) were identified as key contributory factors. Cross-tabular analysis against the final accuracy check variable revealed significant association between the pharmacy location (P < 0.024), dispensary layout (P < 0.025), insufficient staff (P < 0.019), and busier than normal (P < 0.005) variables. Conclusion: The results provide an overview of some of the individual, organisational and technical factors at play at the time of a dispensing error and highlight the need to examine further the relationships between these factors and dispensing error occurrence.