Development, Characterization, and Optimization of a Novel Abiraterone Acetate Formulation to Improve Biopharmaceutical Attributes Aided by Pharmacokinetic Modelling.

Abiraterone acetate has very low bioavailability and drastic food effect to warrant a dosing regimen under fasting state only. Therefore, we aimed to develop and optimize a liquisolid compact formulation of abiraterone acetate to improve biopharmaceutical attributes aided by pharmacokinetic modelling and achieve dose reduction with no food effect on the formulation. Preliminary studies highlighted the importance of the selection of olive oil as a compatible vehicle. The pharmacokinetic model, integrated with gastrointestinal physiology, was used to predict fasted and fed state pharmacokinetic parameters. Optimization of the liquisolid formulation containing abiraterone acetate was carried at more than five times lower dose, i.e. 190 mg, compared to 1000 mg. A central composite design (CCD) was used to identify optimal levels of formulation factors, namely the amount of vehicle (olive oil), the amount of coating agent (silicon dioxide), and the amount of surfactant (polysorbate 80). Graphical optimization using the selected models in conjunction with maximization of the desirability was used to identify the optimized liquisolid formulation. The predicted pharmacokinetic parameters (fasted Cmax 901.83 ng/mL, fasted AUCinf 2723.82 ng·h/mL, fed Cmax 1024.34 ng/mL, and fed AUCinf 3041.83 ng·h/mL) of the optimized formulation were acceptable. Overall, the liquisolid compact formulation of abiraterone acetate was successfully developed and optimized. In vitro solubility and dissolution results aided by pharmacokinetic modelling also showed improved predicted bioavailability with greater than five times reduction in dose and elimination of food effect.

A cross-sectional study of sleep and depression in a rheumatoid arthritis population.

OBJECTIVES: To assess the prevalence of impaired sleep quality and depression in a rheumatoid arthritis population and determine their correlation with Disease Activity Score (DAS) and its components. METHODS: In this single-centre observational cross-sectional study, data was collected by the assessing clinician for DAS28, age and gender in various treatment groups according to use of csDMARDs, biologics and long-term steroids. Presence of impaired sleep quality and depression was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Public Health Questionnaire 9 (PHQ 9). Correlation for DAS and its components with the outcomes was determined by Pearson's correlation coefficient. Multivariate analysis was performed by logistic regression. RESULTS: Two hundred patients were included. The prevalence across all subgroups of poor sleep quality and depression were 86.5% and 30%, respectively, with a correlation coefficient of 0.69 between the two and poor sleep quality amongst all RA patients with comorbid depression. Multivariate analysis found only subjective DAS components, tender joint count (TJC) and patient global health visual analogue score (VAS) to significantly correlate with both outcomes. Age inversely correlated with depression. Long-term steroid use was associated with poorer sleep quality, but there was no significant effect of csDMARDs or biologics. There was no significant difference in prevalence of depression amongst treatment subgroups. CONCLUSION: Poor sleep quality and to a lesser extent depression are prevalent in the general rheumatoid arthritis population. Patients would benefit from clinicians measuring these outcomes routinely as they constitute a significant non-inflammatory burden of living with rheumatoid disease. Key Points • Subjective components of DAS independently correlate with sleep quality and depression, while objective components do not. • Poor sleep quality is highly prevalent in RA and present in all those with comorbid depression. • Poor sleep quality and depression incidence in RA are much lower when DAS is low or remission.

Cogan's syndrome with pyoderma gangrenosum: management of two uncommon disorders with aggressive presentation in a patient.

Pyoderma gangrenosum (PG) coexisting with Cogan's syndrome (CS) is uncommon, although cutaneous manifestations are known to develop in CS. A middle-aged white female patient had chronic relapsing PG requiring ciclosporin and prednisolone. Despite receiving optimal doses of ciclosporin and prednisolone, she developed acute vestibulo-auditory symptoms as a result of CS. Ciclosporin was switched to methotrexate and prednisolone was increased. However, she continued to develop acute scleritis, requiring methylprednisolone pulses, and still had further flares of PG. Her methotrexate was held off when she developed severe pneumonia and she then received a trial of intravenous immunoglobulins (IVIG) for her recurrent leg ulcers. Unfortunately, she failed to respond to IVIG. Her ulcers eventually responded to six doses of monthly intravenous cyclophosphamide induction. Although CS is not an antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, we used pulse cyclophosphamide, based on the experience of cyclophosphamide efficacy in severe ANCA-associated vasculitis (AAV). Following induction, both diseases currently remain under control with azathioprine as maintenance treatment.

Hybrid plasmonic waveguide with centimeter-scale propagation length for nanoscale optical confinement.

A centimeter-scale hybrid plasmonic waveguide (HPW) structure based on a grating is proposed at telecom wavelengths. The high-contrast grating is formed by Si and air placed in an air slot created in the high-index region for attaining nanoscale optical confinement. High-contrast gratings help enhance the propagation length up to 3.6 cm with very low loss of 0.11 dB/mm. Further, the extremely large figure of merit 1,129,623 (>107) with nanoscale confinement of 0.00081/µm2 is introduced. In the present work, finite-element-method-based COMSOL Multiphysics software was applied to simulate and analyze the properties of a HPW structure. The proposed HPW device can be used for next-generation applications of nanolasers and modulators.