The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population - A sustainable product development approach.

Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method.

Normative isometric plantarflexion strength values for professional level, male rugby union athletes.

Objectives: The primary aim was to establish normative values of isometric plantarflexor muscle strength in professional male rugby union players and compare forwards with backs. The secondary aims were to examine how individual playing position or age influences isometric plantarflexor strength.

Design: Cross-sectional.

Novel biomechanical injury risk score demonstrates correlation with lower limb posterior chain injury in 50 elite-level rugby union athletes.

Objectives: Lower limb posterior chain injury (PCI) is common among athletic populations, with multifactorial risk factors including age, previous injury, strength measurements, range of motion and training load. Biomechanics are commonly considered in the prevention and rehabilitation of PCI by performance staff. However, there is no documented testing method to assess for associations between biomechanics and PCI.

BACE1 inhibitors: a head group scan on a series of amides.

A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment.

Evaluation of a cognitive remediation therapy group for adolescents with anorexia nervosa: pilot study.

Objective: Cognitive remediation therapy (CRT) has been used with adults with anorexia nervosa (AN) in individual and group formats; however, evaluation of CRT with adolescents in this population is very limited.

Method: Seven CRT groups were carried out with a total of 30 adolescents with AN. Adolescents' cognitive flexibility and motivation was assessed before and after the group, and they completed qualitative questionnaires after the group to determine their perceptions.

Evidence against a direct role for oxidative stress in cadmium-induced axial malformation in the chick embryo.

Cadmium (Cd) is a powerful inducer of oxidative stress. It also causes ventral body wall defects in chick embryos treated at Hamburger-Hamilton stages 16-17. By measuring malondialdehyde levels (TBARS method) and cotreating with antioxidants (tempol, ascorbate, and N-acetylcysteine), we sought to determine if oxidative stress were directly related to teratogenesis.

Synthesis of novel ketoconazole derivatives as inhibitors of the human Pregnane X Receptor (PXR; NR1I2; also termed SXR, PAR).

PXR, pregnane X receptor, in its activated state, is a validated target for controlling certain drug-drug interactions in humans. In this context, there is a paucity of inhibitors directed toward activated PXR. Using prior observations with ketoconazole as a PXR inhibitor, the target compound 3 was synthesized from (s)-glycidol with overall 56% yield.

Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection.

Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BK(Ca)).

A series of partial structures of ketoconazole has been synthesized and tested for activity on the large conductance calcium-activated potassium channel (BK) in bovine smooth muscle cells. This has provided openers and blockers of the channel. The results suggest that the phenyl and phenoxy moieties are important for interaction with BK, whereas the imidazole group is unimportant.