The meaning and use of the term "blood“in scripture

There have been two, seemingly opposed, schools of thought about the interpretation of "blood" in Scripture. It is held to signify either "life” or "death". This thesis demonstrates the possibility of effecting a synthesis between these interpretations, showing that both ideas must be present. Each occurrence of "blood" has been analysed and divided between sacrificial and non-sacrificial categories. Frequency of occurrence has been carefully considered to determine its implication for statistical evidence. An introduction discusses its significance in primitive societies, showing that it was regarded as the vehicle of life, with an awe-inspiring potency, requiring elaborate taboos and ritual. Old Testament sacrificial contexts indicate a similar belief that the use of blood is carefully regulated because it is the prerogative of God and equals "life" or "life released", whereas in non-sacrificial contexts it signifies "life" or "death" equally. A "Hebrew mind", therefore, requires a synthesis which accommodates both interpretations. In establishing this synthesis it is demonstrated that while some who hold the "blood equals death" theory reject any other interpretation, those who claim that basically "blood equals life" accept that both concepts can be present. A, M, Stibb's criticism of Westcott and others is refuted and his own conclusions questioned. In the analysis of the New Testament use of the term both concepts are again fully present. In non-sacrificial contexts "blood" clearly means "death”, but in sacrificial and eucharistic contexts "life" or "life surrendered" is implied. In discussing the sacrifice of Christ, it is argued that "the blood of Christ" means the life of Christ released by death, offered to G-od and received back by man. Death and life are inextricably connected but the emphasis must be on life surrendered and made available for man’s redemptio

A New Method for Producing Pharmaceutical Co-crystals: Laser Irradiation of Powder Blends

In this work, a high-power CO2 laser was used to irradiate powder blends of co-crystal formers, with the specific aim of trying to cause recrystallization to a co-crystal structure. By varying the power and raster speed of the laser, it was found that sufficient thermal energy could be imparted to the powder to cause molecular rearrangement. It was possible to form co-crystals of caffeine with oxalic acid and caffeine with malonic acid. Interestingly, it was found that, to form co-crystals successfully, the coformers needed to sublime to an appreciable extent, which indicates that the mechanism of rearrangement involves interaction and nucleation in the vapor phase. Laser irradiation thus offers a new route to creation of pharmaceutical co-crystals and a potentially rapid screen for likely co-crystal formation between coforming pairs

Energy consumption and carbon footprint of 3D printing in pharmaceutical manufacture

Achieving carbon neutrality is seen as an important goal in order to mitigate the effects of climate change, as carbon dioxide is a major greenhouse gas that contributes to global warming. Many countries, cities and organizations have set targets to become carbon neutral. The pharmaceutical sector is no exception, being a major contributor of carbon emissions (emitting approximately 55% more than the automotive sector for instance) and hence is in need of strategies to reduce its environmental impact. Three-dimensional (3D) printing is an advanced pharmaceutical fabrication technology that has the potential to replace traditional manufacturing tools. Being a new technology, the environmental impact of 3D printed medicines has not been investigated, which is a barrier to its uptake by the pharmaceutical industry. Here, the energy consumption (and carbon emission) of 3D printers is considered, focusing on technologies that have successfully been demonstrated to produce solid dosage forms. The energy consumption of 6 benchtop 3D printers was measured during standby mode and printing. On standby, energy consumption ranged from 0.03 to 0.17 kWh. The energy required for producing 10 printlets ranged from 0.06 to 3.08 kWh, with printers using high temperatures consuming more energy. Carbon emissions ranged between 11.60 and 112.16 g CO2 (eq) per 10 printlets, comparable with traditional tableting. Further analyses revealed that decreasing printing temperature was found to reduce the energy demand considerably, suggesting that developing formulations that are printable at lower temperatures can reduce CO2 emissions. The study delivers key initial insights into the environmental impact of a potentially transformative manufacturing technology and provides encouraging results in demonstrating that 3D printing can deliver quality medicines without being environmentally detrimental

Advanced machine-learning techniques in drug discovery

The popularity of machine learning (ML) across drug discovery continues to grow, yielding impressive results. As their use increases, so do their limitations become apparent. Such limitations include their need for big data, sparsity in data, and their lack of interpretability. It has also become apparent that the techniques are not truly autonomous, requiring retraining even post deployment. In this review, we detail the use of advanced techniques to circumvent these challenges, with examples drawn from drug discovery and allied disciplines. In addition, we present emerging techniques and their potential role in drug discovery. The techniques presented herein are anticipated to expand the applicability of ML in drug discovery

Laser irradiation to produce amorphous pharmaceuticals

Using a high-power CO2 laser to irradiate powder beds, it was possible to induce phase transformation to the amorphous state. Irradiation of a model drug, indometacin, resulted in formation of a glass. Varying the settings of the laser (power and raster speed) was shown to change the physicochemical properties of the glasses produced and all irradiated glasses were found to be more stable than a reference glass produced by melt-quenching. Irradiation of a powder blend of paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous dispersion. The results suggest that laser-irradiation might be a useful method for making amorphous pharmaceuticals

Effect of Polyethylene Glycol Treatment on Acetic Acid Emissions from Wood

Acetic acid is known to be emitted from sound wood and can accelerate damage to heritage materials, particularly metals. However, few studies have investigated the extent of acetic acid emissions from archaeological wood. This research utilised Solid-Phase-Micro-Extraction (SPME) GC–MS and lead coupon corrosion to identify volatile emissions from polyethylene glycol (PEG)-treated archaeological wood from the Mary Rose collection and assess if they could cause accelerated damage. In addition, the effect of PEG treatment on acetic acid emissions was investigated using sound wood samples. For sound wood, the PEG treatment acted as a barrier to acetic acid emissions, with higher-molecular-weight PEGs preventing more emissions. Archaeological wood, despite its age and high-molecular-weight PEG treatment, still emitted detectable concentrations of acetic acid. Moreover, they emitted a wider array of compounds compared to sound wood, including carbon disulphide. Like sound wood, when the archaeological wood samples were in a sealed environment with lead coupons, they caused accelerated corrosion to lead. This evidences that archaeological wood can emit high enough concentrations of volatile compounds to cause damage and further investigation should be performed to evaluate if this can occur inside museum display cases

3D printing tablets: Predicting printability and drug dissolution from rheological data

Rheology is an indispensable tool for formulation development, which when harnessed, can both predict a material’s performance and provide valuable insight regarding the material’s macrostructure. However, rheological characterizations are under-utilized in 3D printing of drug formulations. In this study, viscosity measurements were used to establish a mathematical model for predicting the printability of fused deposition modelling 3D printed tablets (Printlets). The formulations were composed of polycaprolactone (PCL) with different amounts of ciprofloxacin and polyethylene glycol (PEG), and different molecular weights of PEG. With all printing parameters kept constant, both binary and ternary blends were found to extrude at nozzle temperatures of 130, 150 and 170 °C. In contrast PCL was unextrudable at 130 and 150 °C. Three standard rheological models were applied to the experimental viscosity measurements, which revealed an operating viscosity window of between 100 and 1000 Pa·s at the apparent shear rate of the nozzle. The drug release profiles of the printlets were experimentally measured over seven days. As a proof-of-concept, machine learning models were developed to predict the dissolution behaviour from the viscosity measurements. The machine learning models were discovered to accurately predict the dissolution profile, with the highest f2 similarity score value of 90.9 recorded. Therefore, the study demonstrated that using only the viscosity measurements can be employed for the simultaneous high-throughput screening of formulations that are printable and with the desired release profile

Stereolithographic (SLA) 3D printing of oral modified-release dosage forms.

The aim of this work was to evaluate the suitability of stereolithography (SLA) to fabricate drug-loaded tablets with modified-release characteristics. The SLA printer creates solid objects by using a laser beam to photopolymerise monomers. In this work polyethylene glycol diacrylate (PEGDA) was used as a monomer and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide was used as a photo-initiator. 4-aminosalicylic acid (4-ASA) and paracetamol (acetaminophen) were selected as model drugs. Tablets were successfully printed and formulations with different properties were fabricated by adding polyethylene glycol 300 (PEG 300) to the printing solution. The loading of paracetamol and 4-ASA in the printed tablets was 5.69% and 5.40% respectively. In a realistic dynamic dissolution simulation of the gastrointestinal tract, drug release from the tablets was dependent on the composition of the formulations, but independent of dissolution pH. In conclusion SLA 3DP technology allows the manufacture of drug loaded tablets with specific extended-release profiles. In the future this technology could become a manufacturing technology for the elaboration of oral dosage forms, for industrial production or even for personalised dose

Nanoparticle–membrane interactions

Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes