Stroke is one of the major causes of death and disability, including ischemic stroke, which accounts for 85 -87 % of cases. Currently, there are few treatment options available for minimizing tissue death following a stroke. Emerging data suggest that biomarkers may help improve current clinical outcome of stroke. As such, there is a pressing need to understand the pathophysiology and to explore effective biomarkers following an ischemic brain event. The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, prognosis or treatment. In this review, we summarized the pathophysiology of ischemic stroke and some related biomarkers are examined.
Diphenhydramine (DPH) has been used with ibuprofen (IBU) or naproxen (NAP) in combined therapies to provide better clinical efficacy as an analgesic and sleep aid. We discovered that DPH can form protic ionic liquids (PILs) with IBU and NAP, which opens the opportunity for a new delivery mode of these combination drugs. [DPH][IBU] and [DPH][NAP] PILs exhibit low ionicity, as confirmed by Fourier transform infrared and H NMR spectroscopy, and accompanied by low diffusivity, high viscosity, and poor ionic conductivity. Evaluation of pharmaceutical properties of the two PILs showed that these PILs, despite high solubility and good wettability, exhibited low dissolution rates, owing to the poor dispersion of the PIL drops and the resultant small surface area during dissolution. However, when loaded into a mesoporous carrier, the PIL-carrier composites exhibited improved dissolution rates along with excellent flow properties and easy handling. Oral capsules of both PILs were developed using such composites. Such capsule products exhibited acceptable drug release and bioavailability as demonstrated by a predictive artificial stomach-duodenum dissolution test.
Spherical cocrystallization (SCC),
an integrated crystal and particle
engineering approach, was successfully applied to generate spherical
cocrystal agglomerates (SCA) between a poorly soluble drug, griseofulvin
(GSF) and acesulfame (Acs). The SCC process consists of two steps:
(1) GSF-Acs cocrystal formation by reaction crystallization in a slurry;
(2) agglomeration by adding a bridging liquid. The obtained SCA exhibited
superior mechanical and powder properties over GSF. Inclusion of a
small amount (<1%) HPC in the agglomerates improved both the tabletability
and dissolution performance. Using the SCA, a high GSF loading (55.7%)
direct compression tablet formulation was successfully developed,
which exhibited much improved manufacturability and drug release property
over GSF based tablet formulation.
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