Eicosanoids are potent lipid mediators of inflammation and are known to play an important role in numerous pathophysiological processes. Furthermore, inflammation has been proven to be a mediator of diseases such as hypertension, atherosclerosis, Alzheimer's disease, cancer and rheumatoid arthritis. Hence, these lipid mediators have gained significant attention in recent years. This review focuses on chromatographic and mass spectrometric methods that have been used to analyze arachidonic acid and its metabolites in brain tissue. Recently published analytical methods such as LC-MS/MS and GC-MS/MS are discussed and compared in terms of limit of quantitation and sample preparation procedures, including solid phase extraction and derivatization. Analytical challenges are also highlighted.

Biorelevant dissolution is an indispensable tool utilized during formulation development and optimization for the prediction of in vivo bioavailability of pharmaceutical agents. Within that framework, membrane-permeation dissolution methodologies are widely used to model drug absorption. The current work evaluates polymer membrane surface modifications for production of biomimetic membranes to be employed in biorelevant dissolution studies. Biomimetic membranes exhibit hydrophilic and hydrophobic properties to simulate the intestinal membrane environment. Low temperature plasma treatment of microporous polyethersulfone (PES), nylon and polypropylene (PP) polymer membranes was applied to produce low energy surface layers with permanent hydrophobic and hydrophilic functionalities. Surface modifications on microporous polymer membranes were achieved by plasma treatments using tetrafluoromethane (CF 4 ), perfluorohexane (C 6 F 14 ), dichloromethane (DCM) and water (H 2 O). Surface characterization of treated membranes was evaluated using scanning electron microscopy energy dispersive x-ray spectroscopy (SEM-EDS), water contact angle (CA) and x-ray photoelectron spectroscopy (XPS) techniques. SEM-EDS analysis of polymer membranes treated with fluorinated and chlorinated solvents/gases depicts altered surface morphologies with enriched porosity. SEM-EDS and XPS analyses demonstrate the chemical modification at the surface of treated membranes is strongly influenced by the type of treatment gas or solvent. Results show fluorination as a more effective and less destructive treatment technique. XPS confirmed the presence of elemental fluorine functional groups at the surface of the PES and nylon membranes. Evaluating elemental changes (F/C ratio) from multiple techniques confirms fluorinated plasma treatments are localized to the surface of the membrane and do not significantly affect the bulk properties. In a supplemental study, a detailed comparison of the plasma treated polymer membranes and porcine intestines revealed the biomimetic nature of the modified membranes.

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.

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