Abstract
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 (CF4), perfluorohexane (C6F14), dichloromethane (DCM) and water (H2O). 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.
Highlights
The most popular mode of drug administration is the oral route, denoting the gastrointestinal tract (GIT) as the primary site for drug delivery (York 2013; Rowland 1972; Maisel et al 2015)
Membrane treatment Water vapor plasma treatment of polypropylene membranes To engineer a membrane with asymmetric surface properties, water vapor plasma treatments were performed to enhance the wettability of a hydrophobic polypropylene membrane
The initial increased wettability of the membranes may be attributed to hydrophilic species existing in the pores of the membrane, which are subsequently absorbed into the bulk water during the first contact angle measurement
Summary
The most popular mode of drug administration is the oral route, denoting the gastrointestinal tract (GIT) as the primary site for drug delivery (York 2013; Rowland 1972; Maisel et al 2015). Adjacent to the apical brush border surface, a stagnant layer of aqueous media (unstirred aqueous layer) separates the membrane from the bulk fluid phase and is known to act as a barrier to diffusion (Porter et al 2007). Biomimetic membranes embody essential chemical, physical and topographical properties such as hydrophilicity (unstirred aqueous layer, wettability of membrane from intestinal fluid), hydrophobicity (lipophilicity of the brush border membrane), porosity (neighboring epithelial cells, intestinal crypts/glands in villus) and self-assembly (spontaneous organization of molecules). Novel approaches such as plasma treatment of microporous polymer membranes have been utilized for the production of biomimetic membranes (Obeso et al 2013). An array of plasma treatment approaches (hydrophobic and hydrophilic) can be exploited to manipulate the surface of polymer membranes for a variety of applications
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