A qualitative exploration of the underlying causes of preventable drug-related morbidity in primary care, resulting in hospitalisation

This study has explored the underlying causes of preventable drug-related admissions to hospital, from primary care through semi-structured interviews and review of patients’ medical records. Analysis of the data has revealed that communication failures between different groups of healthcare professionals and between healthcare professionals and patients contribute to preventable drug-related admissions, as do knowledge gaps about medication in both healthcare professionals and patients. In addition, working conditions for community pharmacists severely limit their ability to effectively act as a safety barrier to patients receiving inappropriate medication. Limitations include heavy workloads, lack of access to patients’ clinical information, poor relationships with general practitioners and time restrictions. The results of this study represent an important addition to our understanding of the contribution of human error as an underlying cause of preventable drug-related morbidity, and the factors which contribute to errors occurring in the primary healthcare setting.

Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions

This study probes the molecular interactions between model drugs and poloxamers that facilitate dissolution rate improvements using solid dispersions. Ibuprofen and ketoprofen solid dispersions were prepared at different mole ratios using poloxamers 407 and 188. The carbonyl stretching vibration of the ibuprofen dimer shifted to higher wavenumber in the infrared spectra of 2:1 drug:carrier mole ratio solid dispersions, indicating disruption of the ibuprofen dimer concomitant with hydrogen bond formation between the drug and carrier. Solid dispersions with mole ratios >2:1 drug:carrier (up to 29:1) showed both ibuprofen hydrogen-bonded to the poloxamer, and excess drug present as dimers. X-ray diffraction studies confirmed these findings with no evidence of crystalline drug in 2:1 mole ratio systems whereas higher drug loadings retained crystalline ibuprofen. Similar results were found with ketoprofen-poloxamer solid dispersions. Thermal analysis of ibuprofen-poloxamer 407 solid dispersions and their resultant phase diagram suggested solid solutions and a eutectic system were formed, depending on drug loading. Dissolution studies showed fastest release from the solid solutions; dissolution rates from solid solutions were 12-fold greater than the dissolution of ibuprofen powder whereas the eutectic system gave a 6-fold improvement over the powder. When designing solid dispersions to improve the delivery of poorly-water soluble drugs, the nature of drug:carrier interactions, which are governed by the stochiometry of the composition, can affect the dissolution rate improvement.

The cell cycle and drug discovery: The promise and the hope

In recent years, there have been major developments in the understanding of the cell cycle. It is now known that normal cellular proliferation is tightly regulated by the activation and deactivation of a series of proteins that constitute the cell cycle machinery. The expression and activity of components of the cell cycle can be altered during the development of a variety of diseases where aberrant proliferation contributes to the pathology of the illness. Apart from yielding a new source of untapped therapeutic targets, it is likely that manipulating the activity of such proteins in diseased states will provide an important route for treating proliferative disorders, and the opportunity to develop a novel class of future medicines.

Room temperature synthesis of tri-, tetrasubstituted imidazoles and bis-analogues by mercaptopropylsilica (MPS) in aqueous methanol: application to the synthesis of the drug trifenagrel

The heterogeneous solid catalyst, mercaptopropylsilica (MPS), has been prepared by a modified procedure in water and its structure confirmed by solid state carbon-13 CP-MAS NMR spectrum. This catalyst has been efficiently utilized for the synthesis of a wide variety of tri-, tetrasubstituted imidazoles and their bis-analogues at room temperature. The protocol was further explored for the synthesis of the drug trifenagrel.