ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily caused by accumulation of amyloid-beta (Aß) peptide extracellularly and neurofibrillary tangles intracellularly. Recently, it has been shown that oxidative stress and mitochondrial dysregulation play an important role in pathology of AD. Therefore, modulating various targets such as Aß aggregation, neuro-inflammation, and oxidative stress, genetic factors such as Apolipoprotein E gene (ApoE) are some of the ways to manage AD. Studying the natural products which can act as multifunctional agents could be key toward discovering new therapeutics. Ferulic acid (FA) represents one such natural product, which has exhibited great potential in this regard. Found in the plant cell walls, FA is an antioxidant, free radical scavenger with anti-inflammatory activity. Taking this into consideration, over the years, various derivatives have been reported as anti-AD molecules based on structure of FA. The present review explores the role of FA and its derivatives as therapeutic agents in AD.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Coumaric Acids/pharmacology , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Animals , Antioxidants/pharmacology , Coumaric Acids/chemistry , Free Radical Scavengers/pharmacology , Humans , Mice , Molecular Structure , Neuroprotective Agents/chemistry , Oxidative Stress/drug effects , Plant Extracts/chemistry , Protein Aggregates/drug effects , Structure-Activity RelationshipABSTRACT
Efavirenz is a non-nucleoside reverse transcriptase inhibitor and categorized in to BCS class II drug. The aim of the present investigation was to apply quality by design approach to enhance the solubility, dissolution and stability of amorphous solid dispersions (ASDs) of efavirenz using a combination of Soluplus® and HPMCAS-HF polymers. In design of experiments, the user defined quadratic model was used to study the effect of variable concentrations of Soluplus® and HPMCAS-HF for the formation of ASDs of efavirenz. Similarly, a prototype ASD was made using Soluplus® as a carrier with efavirenz loading of 30%. The efavirenz ASDs granular extrudates were evaluated for saturation solubility as well as dissolution rate studies. X-ray powder diffraction, Differential scanning calorimetry, Fourier transform infrared, Atomic force microscopy and FTIR imaging to determine the solid state of efavirenz in the ASDs. DSC and XRD data confirmed that bulk crystalline efavirenz transformed to the amorphous form during the hot melt extrusion processing. Prototype ASD batch showed instability upon storage as per ICH guidelines over a period of 6months, observations inferred from DSC, XRD and in vitro dissolution studies. The maximum dissolution rate was observed when Soluplus® and HPMCAS-HF was in ratio of (60:20) as optimized by design of experiments study. Moreover, the optimized ASDs batch were stable at 40°C, 75% RH for a period of 6months without any dissolution rate changes, and remained into amorphous state.
