A study on the cost sharing model for supply lead time reduction with component commonality

This paper studies a two-level supply chain consisting of components supplier and product assembly manufacturer, while the manufacturer shares the investment on shortening supply lead time. The objective of this research is to investigate the benefits of cost sharing strategy and adopting component commonality. The result of numerical analysis demonstrates that using component commonality can help reduce the total cost, especially when the manufacture shares a higher fraction of the cost of investment in shortening supply lead time.

Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces

Freeze-dried (lyophilised) wafers and solvent cast films from sodium alginate (ALG) and sodium carboxymethylcellulose (CMC) have been developed as potential drug delivery systems for mucosal surfaces including wounds. The wafers (ALG, CMC) and films (CMC) were prepared by freeze-drying and drying in air (solvent evaporation) respectively, aqueous gels of the polymers containing paracetamol as a model drug. Microscopic architecture was examined using scanning electron microscopy, hydration characteristics with confocal laser scanning microscopy and dynamic vapour sorption. Texture analysis was employed to investigate mechanical characteristics of the wafers during compression. Differential scanning calorimetry was used to investigate polymorphic changes of paracetamol occurring during formulation of the wafers and films. The porous freeze-dried wafers exhibited higher drug loading and water absorption capacity than the corresponding solvent evaporated films. Moisture absorption, ease of hydration and mechanical behaviour were affected by the polymer and drug concentration. Two polymorphs of paracetamol were observed in the wafers and films, due to partial conversion of the original monoclinic to the orthorhombic polymorph during the formulation process. The results showed the potential of employing the freeze-dried wafers and solvent evaporated films in diverse mucosal applications due to their ease of hydration and based on different physical mechanical properties exhibited by both type of formulations.

Simultaneous monitoring of drug and solvent diffusion across a model membrane using ATR-FTIR spectroscopy

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to simultaneously follow the diffusion of model drugs and solvent across polydimethylsiloxane (silicone) membrane. Three model drugs, cyanophenol (CNP), methyl nicotinate (MN) and butyl paraben (BP) were selected to cover a range of lipophilicities. Isostearyl isostearate (ISIS) was chosen as the solvent because its large molecular weight should facilitate observation of whether the drug molecules are able to diffuse through the membrane independently of the solvent. The diffusion of the three drugs and the solvent was successfully described by a Fickian model. The effects of parameters such as the absorption wavelength used to follow diffusion on the calculated diffusion coefficient were investigated. Absorption wavelength which affects the depth of penetration of the infrared radiation into the membrane did not significantly affect the calculated diffusion coefficient over the wavelength range tested. Each of the model drugs was observed to diffuse independently of the solvent across the membrane. The diffusion of a CNP-ISIS hydrogen bonded complex across the membrane was also monitored. The relative diffusion rates of the solute and solvent across the membrane can largely be accounted for by the molecular size of the permeant.

The application of electrostatic dry powder deposition technology to coat drug-eluting stents

Purpose: A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles. Methods: Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces. Results: The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion. Conclusions: EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.

The role of space charge formation in the generation of thermally stimulated current (TSC) spectroscopy data for a model amorphous drug system

Thermally stimulated current (TSC) spectroscopy is attracting increasing attention as a means of materials characterization, particularly in terms of measuring slow relaxation processes in solid samples. However, wider use of the technique within the pharmaceutical field has been inhibited by difficulties associated with the interpretation of TSC data, particularly in terms of deconvoluting dipolar relaxation processes from charge distribution phenomena. Here, we present evidence that space charge and electrode contact effects may play a significant role in the generation of peaks that have thus far proved difficult to interpret. We also introduce the use of a stabilization temperature in order to control the space charge magnitude. We have studied amorphous indometacin as a model drug compound and have varied the measurement parameters (stabilization and polarization temperatures), interpreting the changes in spectral composition in terms of charge redistribution processes. More specifically, we suggested that charge drift and diffusion processes, charge injection from the electrodes and high activation energy charge redistribution processes may all contribute to the appearance of shoulders and 'spurious' peaks. We present recommendations for eliminating or reducing these effects that may allow more confident interpretation of TSC data.

In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks

The aim of the current study was to evaluate the potential of the dynamic lipolysis model to simulate the absorption of a poorly soluble model drug compound, probucol, from three lipid-based formulations and to predict the in vitro-in vivo correlation (IVIVC) using neuro-fuzzy networks. An oil solution and two self-micro and nano-emulsifying drug delivery systems were tested in the lipolysis model. The release of probucol to the aqueous (micellar) phase was monitored during the progress of lipolysis. These release profiles compared with plasma profiles obtained in a previous bioavailability study conducted in mini-pigs at the same conditions. The release rate and extent of release from the oil formulation were found to be significantly lower than from SMEDDS and SNEDDS. The rank order of probucol released (SMEDDS approximately SNEDDS > oil formulation) was similar to the rank order of bioavailability from the in vivo study. The employed neuro-fuzzy model (AFM-IVIVC) achieved significantly high prediction ability for different data formations (correlation greater than 0.91 and prediction error close to zero), without employing complex configurations. These preliminary results suggest that the dynamic lipolysis model combined with the AFM-IVIVC can be a useful tool in the prediction of the in vivo behavior of lipid-based formulations.

The use of fluorescence microscopy to define polymer localisation to the late endocytic compartments in cells that are targets for drug delivery

Macromolecular therapeutics and nano-sized drug delivery systems often require localisation to specific intracellular compartments. In particular, efficient endosomal escape, retrograde trafficking, or late endocytic/lysosomal activation are often prerequisites for pharmacological activity. The aim of this study was to define a fluorescence microscopy technique able to confirm the localisation of water-soluble polymeric carriers to late endocytic intracellular compartments. Three polymeric carriers of different molecular weight and character were studied: dextrin (Mw~50,000 g/mol), a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer (Mw approximately 35,000 g/mol) and polyethylene glycol (PEG) (Mw 5000 g/mol). They were labelled with Oregon Green (OG) (0.3-3 wt.%; <3% free OG in respect of total). A panel of relevant target cells were used: THP-1, ARPE-19, and MCF-7 cells, and primary bovine chondrocytes (currently being used to evaluate novel polymer therapeutics) as well as NRK and Vero cells as reference controls. Specific intracellular compartments were marked using either endocytosed physiological standards, Marine Blue (MB) or Texas-red (TxR)-Wheat germ agglutinin (WGA), TxR-Bovine Serum Albumin (BSA), TxR-dextran, ricin holotoxin, C6-7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)-labelled ceramide and TxR-shiga toxin B chain, or post-fixation immuno-staining for early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins (LAMP-1, Lgp-120 or CD63) or the Golgi marker GM130. Co-localisation with polymer-OG conjugates confirmed transfer to discreet, late endocytic (including lysosomal) compartments in all cells types. The technique described here is a particularly powerful tool as it circumvents fixation artefacts ensuring the retention of water-soluble polymers within the vesicles they occupy.

Drug calculations part 2: alternative strategies to the formula

Drug calculations are an essential skill for nurses. The clinical skill of performing a drug calculation has come under recent scrutiny,resulting in the development of essential skills clusters inwhich pre-registration nurses must be competent before qualifying (Nursing and Midwifery Council 2007). The focuson drug calculation skills places renewed emphasis on how these skills are taught in higher education institutions and how they are learned by students theoretically and in clinical practice.

Drug calculations part 1: a critique of the formula used by nurses

The role of mathematics is integral to nursing practice, and careful and accurate calculations are important to help prevent medication errors. This two-part article examines different methods for solving drug calculation problems. The first part critiques the commonly taught nursing drug calculation formula. Part 2, to be published next week, explores a range of other methods that are used in practice to calculate drug dosages.

The assessment and development of drug calculation skills in nurse education: a critical debate

The drug calculation skill of nurses continues to be a national concern. The continued concern has led to the introduction of mandatory drug calculation skills tests which students must pass in order to go on to the nursing register. However, there is little evidence to demonstrate that nurses are poor at solving drug calculation in practice. This paper argues that nurse educationalists have inadvertently created a problem that arguably does not exist in practice through use of invalid written drug assessment tests and have introduced their own pedagogical practice of solving written drug calculations. This paper will draw on literature across mathematics, philosophy, psychology and nurse education to demonstrate why written drug assessments are invalid, why learning must take place predominantly in the clinical area and why the key focus on numeracy and formal mathematical skills as essential knowledge for nurses is potentially unnecessary.

Can effective teaching and learning strategies help student nurses to retain drug calculation skills?

Student nurses need to develop and retain drug calculation skills in order accurately to calculate drug dosages in clinical practice. If student nurses are to qualify and be fit to practise accurate drug calculation skills, then educational strategies need to not only show that the skills of student nurses have improved but that these skills have been retained over a period of time. A quasi-experimental approach was used to test the effectiveness of a range of strategies in improving retention of drug calculation skills. The results from an IV additive drug calculation test were used to compare the drug calculation skills of student nurses between two groups of students who had received different approaches to teaching drug calculation skills. The sample group received specific teaching and learning strategies in relation to drug calculation skills and the second group received only lectures on drug calculation skills. All test results for students were anonymous. The results from the test for both groups were statistically analysed using the Mann Whitney test to ascertain whether the range of strategies improved the results for the IV additive test. The results were further analysed and compared to ascertain the types and numbers of errors made in each of the sample groups. The results showed that there is a highly significant difference between the two samples using a two-tailed test (U=39.5, p<0.001). The strategies implemented therefore did make a difference to the retention of drug calculation skills in the students in the intervention group. Further research is required into the retention of drug calculation skills by students and nurses, but there does appears to be evidence to suggest that sound teaching and learning strategies do result in better retention of drug calculation skills.

Managing the supply side for product development in China: a Guanxi network approach

Based on the IMP research tradition this paper regards relationships and networks as key issues in the product development and supply management agenda. Within business networks, co-development is only possible to be analysed when emphasis is placed on interdependences and interactive relationships. Co-development usually implies close relationships that allow companies to rely on each other's resources. Close relationships imply interdependences, which may improve companies' technical and product development. By looking at the actual interactions - between a UK company and its Chinese suppliers - that led to an innovative solution and a successful product launch, evolving relationship patterns are identified and analysed in a case study. Both the literature review and case study findings highlight the importance of the 'guanxi' concept (meaning interpersonal relationships in Mandarin) when analysing business-to-business networks in China. Hence, it is suggested that guanxi-based thinking and acting should be incorporated into the interaction model when considering business networking that embrace China. 'Guanxi' broadens the validity of the interaction model, in terms of geographical proximity, and deepens its theoretical base. The case study provides valuable insights for supply management under a product development context in China. In practice, the main point of interest is that Chinese suppliers are important 'resource' providers as well as 'network' providers. Hence, it is suggested that guanxi practice should be reflected into theoretical developments.

Trade credit linkages along the supply chain: evidence for the Italian textile sector

We examine the trade credit linkages among firms within a supply chain to reckon the effect of such linkages on the propagation of liquidity shocks from downstream to upstream firms. We choose a sample appropriate for this task, consisting of a large data set of Italian firms from the textile industry, a well known example of a comprehensive manufacturing cluster featuring a large number of small and specialized firms at each level of the supply chain. The results of the analysis indicate that the level of trade credit that firms provide to their suppliers is positively related to the level of trade credit granted to their clients: when the level of trade credit granted to clients divided by sales goes up by 1, the level of trade credit provided to suppliers divided by cost-of goods-sold goes up by an amount that varies between 0,22 and 0,52. Since all firms along the chain are linked by trade credit relationships, an increase in the level of trade credit granted by wholesalers generates a liquidity cascade throughout the chain. We designate the overall increase in the level of trade credit among all firms in the chain as a result of a unitary impulse in the level of trade credit granted by wholesalers as the multiplier effect of trade credit for the industry chain. We estimate such multiplier to vary between 1.28 and 2.04. We also investigate the effect of final demand on the level of trade credit sourced by firms at various levels of the chain and, in particular, whether such effect is amplified for firms further up in the chain as a result of liquidity propagation via trade credit linkages. We uncover evidence of such amplification when the links of liquidity transmission along the chain are individually modeled and estimated. An unitary increase in wholesalers’ sales is found to produce an effect on trade payables among firms at the top of the chain (i.e., Preparers and Spinners) that is more than twice as big as the corresponding effect among firms at the bottom of the chain (i.e., Wholesalers).

Wound healing dressings and drug delivery systems: a review

The variety of wound types has resulted in a wide range of wound dressings with new products frequently introduced to target different aspects of the wound healing process. The ideal dressing should achieve rapid healing at reasonable cost with minimal inconvenience to the patient. This article offers a review of the common wound management dressings and emerging technologies for achieving improved wound healing. It also reviews many of the dressings and novel polymers used for the delivery of drugs to acute, chronic and other types of wound. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. There is also a brief section on the use of biological polymers as tissue engineered scaffolds and skin grafts. Pharmacological agents such as antibiotics, vitamins, minerals, growth factors and other wound healing accelerators that take active part in the healing process are discussed. Direct delivery of these agents to the wound site is desirable, particularly when systemic delivery could cause organ damage due to toxicological concerns associated with the preferred agents. This review concerns the requirement for formulations with improved properties for effective and accurate delivery of the required therapeutic agents. General formulation approaches towards achieving optimum physical properties and controlled delivery characteristics for an active wound healing dosage form are also considered briefly.