QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

Background: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability.

Ligand and structure-based computational designing of multi-target molecules directing FFAR-1, FFAR-4 and PPAR-G as modulators of insulin receptor activity.

Multi-agent therapies are an important treatment modality in many diseases based on the assumption that combining agents may result in increased therapeutic benefit by overcoming the mechanism of resistance and providing superior efficiency. Extensively validated 3D pharmacophore models for free fatty acid receptor-1 (FFAR-1), free fatty acid receptor-4 (FFAR-4), and peroxisome proliferator-activated receptor-G (PPAR-G) was developed. The pharmacophore model for FFAR-1 ( = 0.

Dimethyl fumarate exerts neuroprotection by modulating calcineurin/NFAT1 and NFκB dependent BACE1 activity in Aβ treated neuroblastoma SH-SY5Y cells.

Ample studies indicate that calcineurin, a Ca/calmodulin-sensitive phosphatase, plays a key role in the initiation and/or clinical progression of Alzheimer's disease, and alteration of calcineurin has been confirmed in Alzheimer's disease brain, impacting tau proteins and amyloid beta (Aβ) levels and resulting in neuronal cell death. As, it is sensible to deliberate the likelihood of calcineurin inhibition as a pharmacological target in the progress of novel Alzheimer's disease therapies, we investigated the neuroprotective efficacy of dimethyl fumarate (DMF) via calcineurin dependent downstream targets in oligomeric Aβ treated neuroblastoma SH-SY5Y cells. DMF pre-treatment reduced LDH release, increased cell survival and decreased calcineurin activity in Aβ-incubated cells.

Dimethyl Fumarate Mitigates Tauopathy in Aβ-Induced Neuroblastoma SH-SY5Y Cells.

Alzheimer's disease pathogenesis is measured by two key hallmarks viz extracellular senile plaques composed of insoluble amyloid beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau, resulting in microtubule destabilization, synaptic damage and neurodegeneration. Accumulation of Aβ is an introducing pathological incident in Alzheimer's disease; hence, the effect of dimethyl fumarate (DMF) on Aβ-induced alterations in phosphorylated tau, related protein kinases, fibrillogenesis and microtubule assembly in neuroblastoma SH-SY5Y cells was determined. DMF attenuated Aβ-induced neuronal apoptosis by down-regulating protein levels of Bcl-2/Bax, cleaved caspase-3 and caspase-9.

Formulation and evaluation of aceclofenac mouth-dissolving tablet.

Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities similar to indomethacin and diclofenac, and due to its preferential Cox-2 blockade, it has a better safety than conventional Non steroidal anti-inflammatory drug (NSAIDs) with respect to adverse effect on gastrointestinal and cardiovascular systems. Aceclofenac is superior from other NSAIDs as it has selectivity for Cox-2, a beneficial Cox inhibitor is well tolerated, has better Gastrointestinal (GI) tolerability and improved cardiovascular safety when compared with other selective Cox-2 inhibitor. To provide the patient with the most convenient mode of administration, there is need to develop a fast-disintegrating dosage form, particularly one that disintegrates and dissolves/disperses in saliva and can be administered without water, anywhere, any time.