A new rapidly absorbed paracetamol tablet containing sodium bicarbonate. II. Dissolution studies and in vitro/in vivo correlation

The objective of this study was to compare the in vitro dissolution profile of a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with that of a conventional paracetamol tablet (P), and to relate these by deconvolution and mapping to in vivo release. The dissolution methods used include the standard procedure described in the USP monograph for paracetamol tablets, employing buffer at pH5.8 or 0.05 M HCl at stirrer speeds between 10 and 50 rpm. The mapping process was developed and implemented in Microsoft Excel® worksheets that iteratively calculated the optimal values of scale and shape factors which linked in vivo time to in vitro time. The in vitro-in vivo correlation (IVIVC) was carried out simultaneously for both formulations to produce common mapping factors. The USP method, using buffer at pH5.8, demonstrated no difference between the two products. However, using an acidic medium the rate of dissolution of P but not of PS decreased with decreasing stirrer speed. A significant correlation (r=0.773; p<.00001) was established between in vivo release and in vitro dissolution using the profiles obtained with 0.05 M HCl and a stirrer speed of 30 rpm. The scale factor for optimal simultaneous IVIVC in the fasting state was 2.54 and the shape factor was 0.16; corresponding values for mapping in the fed state were 3.37 and 0.13 (implying a larger in vitro-in vivo time difference but reduced shape difference in the fed state). The current IVIVC explains, in part, the observed in vivo variability of the two products. The approach to mapping may also be extended to different batches of these products, to predict the impact of any changes of in vitro dissolution on in vivo release and plasma drug concentration-time profiles.

Supply chain "mega-trends":current status and future trends

The supply chain management (SCM) concept has become embedded in the thinking of many organisations in recent years. Originally introduced by management consultants in the early 1980s, SCM has a strong focus on integration of processes across functions within firms, as well as between the organisations that comprise the wider extended enterprise. There is a significant body of research to support the notion that the consistent delivery of value to customers is predicated on higher levels of intra-firm and inter-firm integration. Putting the supply chain integration (SCI) concept into practice is critically dependent on the ability of firms to manage material, money and information flows in a holistic manner. It also depends on the way in which relationships between key supply chain actors are managed. This article explores the “mega-trends” that are evident across most sectors and which have a potentially significant impact on the ability of organisations to put SCM theory into practice. The late Don Bowersox and his colleagues from Michigan State University introduced the idea of supply chain “mega-trends” over a decade ago in their widely cited article in the Journal of Business Logistics (Bowersox et al., 2000). This article explores the current status of these “mega-trends” in an Irish context based on research being undertaken at the National Institute for Transport and Logistics (NITL). It also identifies some key factors that are likely to impact upon progress in these key areas in the medium term.

A review of current knowledge on Electronic Vision Enhancement Systems for the visually impaired

Magnification can be provided to assist those with visual impairment to make the best use of remaining vision. Electronic transverse magnification of an object was first conceived for use in low vision in the late 1950s, but has developed slowly and is not extensively prescribed because of its relatively high cost and lack of portability. Electronic devices providing transverse magnification have been termed closed-circuit televisions (CCTVs) because of the direct cable link between the camera imaging system and monitor viewing system, but this description generally refers to surveillance devices and does not indicate the provision of features such as magnification and contrast enhancement. Therefore, the term Electronic Vision Enhancement Systems (EVES) is proposed to better distinguish and describe such devices. This paper reviews current knowledge on EVES for the visually impaired in terms of: classification; hardware and software (development of technology, magnification and field-of-view, contrast and image enhancement); user aspects (users and usage, reading speed and duration, and training); and potential future development of EVES. © 2003 The College of Optometrists.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS

In an aging western population, a significant number of patients continue to suffer from angina once all revascularization and optimal medical treatment options are exhausted. Under experimental conditions, oral supplementation with inorganic nitrate was shown to exhibit a blood pressure-lowering effect, and has also been shown to promote angiogenesis, improve endothelial dysfunction and mitochondrial efficiency in skeletal muscle. It is unknown whether similar changes occur in cardiac muscle. In the current study, we investigate whether oral sodium nitrate treatment will improve myocardial ischemia in patients with stable angina.