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PharmTech.com Trends in Formulation 2022 eBook Pharmaceutical Technology ® 25 Formul ation and drug delivery concentration (CMC). With a hydrophilic/lipophilic balance (HLB) of 13.2, TPGS can be considered as an oil in water emulsifier and can therefore be used to disperse a wide range of lipophiles in an aqueous ma- trix. This property of TPGS has been extensively ap- plied in the preparation of a wide variety of emulsions including CoQ10, carotenoids, and cannabinoids (14). TPGS as an absorption enhancer In the small intestine, there are two primary mech- anisms, shown in Figure 3, by which a drug mole- cule can move across an epithelial cell in the process known as absorption. If the molecule passes through the junction between two cells, the absorption is said to be paracellular. If the molecule passes through a cell, the absorption is transcellular (15). Both absorp- tion mechanisms can be enhanced by TPGS: it can stimulate the opening of tight junctions bet ween cells and thereby facilitate paracellular transport, and it can inhibit the membrane transporter known as the permeability glycoprotein (P-gp) eff lux pump that actively expel materials post-absor ption (16). These P-gp transporters are found in many cells in the body, including the GI tract, the liver, the kid- ney, and the capillary endothelial cells of the blood- brain barrier, where they protect underlying cells by reversing the absorption of potentially toxic sub- stances such as endogenous metabolites and xeno- biotics. Suppressing or inhibiting this eff lux mech- anism is an established approach to increasing the permeabilit y and absor ption of a dr ug substance, and several mechanisms for the role of TPGS in this process have been proposed (17,18). TPGS for overcoming MDR to chemotherapy drugs Chemotherapy, or the use of cytotoxic drugs for the treatment of cancer, is a major field of medical re- search and an important aspect of cancer therapy. Although chemotherapy drugs are designed to target rapidly dividing cancer cells, some healthy cells are also damaged, resulting in many of the unpleasant side effects and serious complications associated with chemotherapy. In an adaptive response to con- tinuing treatment, tumor cells can upregulate the P-gp membrane transporter production, reducing the intracellular accumulation of the drugs and de- creasing their cytotoxic effect. This increases the susceptibility of healthy cells, and the extent and the severity of adverse effects. In the same way that TPGS increases absorption in the epithelial cells of the small intestine, it can inhibit the enhanced P-gly- coprotein eff lux mechanism in tumor cells, revers- ing this acquired multi-drug resistance. This allows a more effective application of chemotherapeutic Drug Digest: Advancing OSD: Continuous Production Considerations and Dose-Level Authentication Drug Digest is a tech talk video series with the Pharmaceutical Technology editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products. In this installment, the editors interview oral solid dosage development experts from Syntegon and Colorcon, with discussions centered on continuous oral solid dosage (OSD) production, containment safety, and authentication at the dose level. Alex Trombley, OSD process specialist/business development manager of Syntegon, runs through the benefits of continuous OSD production and key considerations for containment and operator safety, while Ali Rajabi-Siahboomi, vice president and chief innovation officer, and Gary Pond, global lead, authentication, both of Colorcon, highlight the importance of authentication at the dose level. Click here to watch the interviews.