Fabrication of ticagrelor bioadhesive solid dispersion based on coaxial electrostatic spray to improve drug release and enhance oral bioavailability.

Due to the low solubility and poor bioavailability of Ticagrelor (TIC), the current study developed a structured bioadhesive core-shell drug delivery system to address it. Ticagreior solid dispersion (T-SD) was fabricated using the uniaxial electrostatic spray method. Ticagrelor bio adhesive solid dispersion (T-BSD) was also prepared using the coaxial electrostatic spray technique. The adhesion of T-BSD to each intestinal segment was determined using biological adhesion test. The compartment model was used to study the plasma concentration-time curve and related pharmacokinetic parameters. The results of bioadhesion tests showed a positive adhesion effect of T-BSD in each intestinal segment. The maximum plasma concentration (Cmax) of T-BSD was increased to 777.08ng/mL compared with the free drug (367ng/mL). Similarly, t1/2, MRT and Tmax of T-BSD (12.1h, 9.4h, 4h) were higher than the free drug (11.2h, 8.6h, 1h), respectively. The relative bioavailability of T-BSD was further increased to 430% compared with the free drug. The findings collectively revealed that the coaxial-electrospray technique could be a promising way to improve the bioavailability of TIC.

Integrating Palliative Care Into a Neurosurgical Intensive Care Unit (NS-ICU): A Quality Improvement (QI) Project.

OBJECTIVES: We conducted a pilot quality improvement (QI) project with the aim of improving accessibility of palliative care to critically ill neurosurgical patients. METHODS: The QI project was conducted in the neurosurgical intensive care unit (NS-ICU). Prior to the QI project, referral rates to palliative care were low. The ICU-Palliative Care collaborative comprising of the palliative and intensive care team led the QI project from 2013 to 2015. The interventions included engaging key stake-holders, establishing formal screening and referral criteria, standardizing workflows and having combined meetings with interdisciplinary teams in ICU to discuss patients' care plans. The Palliative care team would review patients for symptom optimization, attend joint family conferences with the ICU team and support patients and families post-ICU care. We also collected data in the post-QI period from 2016 to 2018 to review the sustainability of the interventions. RESULTS: Interventions from our QI project and the ICU-Palliative Care collaborative resulted in a significant increase in the number of referrals from 9 in 2012 to 44 in 2014 and 47 the year later. The collaboration was beneficial in facilitating transfers out of ICU with more deaths outside ICU on comfort-directed care (96%) than patients not referred (75.7%, p < 0.05). Significantly more patients had a Do-Not-Resuscitation (DNR) order upon transfer out of ICU (89.7%) compared to patients not referred (74.2.%, p < 0.001), and had fewer investigations in the last 48 hours of life (p < 0.001). Per-day ICU cost was decreased for referred patients (p < 0.05). CONCLUSIONS: Multi-faceted QI interventions increased referral rates to palliative care. Referred patients had fewer investigations at the end-of-life and per-day ICU costs.