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Hot Melt Extrusion can be simply defined as the process of forming a new material by forcing it through an orifice or die under controlled conditions, such as temperature, mixing, feed-rate and pressure. Hot Melt Extrusion is the process of embedding drug in a polymeric carrier. Hot Melt Extrusion is the process of converting a raw material into a product of uniform shape and density by forcing it through a die under controlled conditions. In recent years, interest in hot melt extrusion techniques for pharmaceutical applications has grown significantly. Hot melt extrusion (HME) is an established manufacturing process that has been used in the plastics and food industry since the 1930s. It was first developed in the early 20th century by the plastics industry as a means of producing different shapes for a variety of industrial and domestic applications.
After oral administration, the majority of drug molecules are absorbed across the small intestine and enter the systemic circulation via the portal vein and the liver. For some highly lipophilic drugs (typically log PN5, lipid solubility 50 mg/g), however, association with lymph lipoproteins in the enterocyte leads to transport to the systemic circulation via the intestinal lymph. The attendant delivery benefits associated with lymphatic drug transport include a reduction in first pass metabolism and lymphatic exposure to drug concentrations orders of magnitude higher than that attained in systemic blood. In the current review we briefly describe the mechanisms by which drug molecules access the lymph and the formulation strategies that may be utilised to enhance lymphatic drug transport. Specific focus is directed toward recent advances in understanding regarding the impact of lipid source (both endogenous and exogenous) and intracellular lipid trafficking pathways on lymphatic drug transport and enterocyte based first pass metabolism.
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