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Innovations and Future Prospects of Dermal Delivery Systems
Published in Tapash K. Ghosh, Dermal Drug Delivery, 2020
Rashmi Upasani, Anushree Herwadkar, Neha Singh, Ajay K. Banga
This dosage form presents significant advantages to dermal and transdermal drug delivery such as providing a highly solubilizing milieu for poorly soluble drugs and enhancing the cutaneous absorption of both hydrophilic and lipophilic drugs (as compared to conventional vehicles). The amphiphilic components in microemulsions act as penetration enhancers. The drug exhibits a high internal mobility within the vehicle resulting in high permeation rates due to solvent drag effect. Till date much of the research in the microemulsion arena has been limited to in vitro studies and only a few in vivo studies have been reported for dermal delivery using these vehicles (Kreilgaard 2002).
Absorption of Macromolecules by Mammalian Intestinal Epithelium
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Absorption through the gastrointestinal mucosa occurs by active transport, diffusion, and by solvent drag. Briefly, active transport imparts energy to the substance as it being transported for the purpose of concentrating it on the other side of the membrane or moving it against an electrical potential. On the other hand, transport by “diffusion” means simply transport of substances through the membrane as a result of molecular movement along an electrochemical gradient. Transport by solvent drag occurs anytime a solvent is absorbed because of physical absorptive forces. The movement of the solvent will “drag” dissolved substances along—the basis of many formulation approaches for pharmaceuticals.
Importance of the Microcirculation to Intestinal Secretion
Published in T. S. Gaginella, Regulatory Mechanisms — in — Gastrointestinal Function, 2017
Active transport of glucose and amino acids increases epithelial conductance through a specific effect of increasing tight junctional permeability.18This process requires mucosal nutrients, Na, and metabolic energy, and is mediated through activation of Na-coupled organic transport and cytoskeletal structures. This response is dependent on adequate oxygenation, and therefore ischemia may reduce mucosal permeability through tight junctions.142Dilations form within the tight junctions, and their resistance to paracellular transport decreases. This process increases the absorption of nutrients past the tight junctions through increased solvent drag. The solvent drag is driven by the active transport into, and consequent osmotic pressure in, the lateral spaces. Pressure-driven secretion across the epithelium would be increased when tight junction dilations occur, but the concurrent active absorption may mask this secretion.143
Dialysis associated β2-microglobulin amyloidosis occurs even in the era of high-flux dialyzers
Published in Amyloid, 2018
Lucas L. Falke, Sybren L. N. Maas, Stefano Rosati, Susan J. J. Logtenberg
Historically, hemodialysis was performed using drum dialyzers with cellulose-based filters. Soon paradigm shifted towards disk and later hollow fiber dialysis allowing for blood compartment and dialysis-time reduction. Perpendicular, dialyzer membrane material use shifted towards synthetic polymers (e.g. poly(ether)sulfone) allowing improvement of characteristics such as biocompatibility, pore-size, membrane structure symmetry and permeability, flux and associated convection (i.e. water permeability and solvent drag), and adherence [3]. With the improvement of dialyzer characteristics, focus is shifting towards adequate clearance of detrimental LMWPs, a process dependent upon convection and adherence (as opposed to small uremic toxins eliminated by diffusion). β2M is universally used as surrogate marker for LMWP clearance [4].
Low colonic absorption drugs: risks and opportunities in the development of oral extended release products
Published in Expert Opinion on Drug Delivery, 2018
Jin Xu, Yiqing Lin, Pierre Boulas, Matthew L. Peterson
Absorption enhancers can improve the oral absorption via several mechanisms, such as preventing degradation or metabolism, transient opening of tight junctions, solvent drag, disruption of lipid bilayer, and/or formation of a membrane permeable complex [116,117]. Various absorption enhancers, for example, bile salts, surfactants, cosolvents, fatty acids, and chelators, have been proven to improve the bioavailability of poorly absorbed small molecules, proteins and peptides, and macromolecules in preclinical or clinical studies. For instance, Neoral® (cyclosporine) has shown increased bioavailability [118] using a self-nanoemulsifying drug delivery system. Nanosized lipid droplets can facilitate solubilization. The medium chain fatty acid-based excipients likely help increase intestinal permeability and inhibit P-glycoprotein efflux and CYP3A4 metabolism [119]. Together, the in vivo absorption and oral bioavailability of cyclosporine are improved. To date, only a few oral drug products utilizing absorption enhancement technologies are on the market or under clinical evaluations [117,119]. The details of current pipeline using absorption enhancement technologies, as well as the current status and challenges of absorption enhancers, have been summarized and reviewed [116,117,119–121]. The reader is referred to previous reviews for these topics.