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Figure 3 Empty capsules loaded and separated by vacuum Segment & cleaning station (by air and vacuum) Filled capsules discharge Capsule cap and body closing station Station for liquid filling Optional station for pellet, tablet, or capsule filling Station for liquid filling No-capsule detection Ejection of unopened capsules Liquid filling process (sealing not shown) in vitro measurements of permeability and solubility. In this way, the BCS helps formulators predict the in vivo pharmacokinetic performance of drug products. Because most of the easy molecules have already been discovered—only 5 percent of the APIs under develop- ment belong to the Class I (high bioavailability) and 70 percent belong to Class II—the bioavailability of today's APIs is typically poor. To improve their bioavailability, it is necessary to increase their solubility. R&D scientists have a number of options to do so, and one of them is use to used lipids in the formulation [1-8]. Lipid-based formulations The principle behind lipid-based formulations is not complicated: It involves dissolving the API in a mixture of solvents. The mixture may comprise triglycerides, mixed glycerides, co-solvents (i.e., polyethylene glycol, propy- lene glycol), water-insoluble surfactants (i.e., Tween 80), water-soluble surfactants (i.e., Cremophor EH 40), solu- bility enhancers (i.e., Acconon MC 8/2), and other addi- tives, such as α-tocopherol. For formulators, the key goals are developing a mix- ture that dissolves the API, increases its bioavailability, and can be placed in a compatible container, typically a capsule. The final steps are identifying a suitable capsule and capsule filler to handle the liquid formulation. In addition to improving bioavailability, lipid-based formulations reduce the food effect. This effect—in which the co-administration of the drug product and food affects the absorption of the API—could lead to a sub-therapeutic concentration of API in blood plasma (C max ). This is a serious problem for APIs that have a nar- row therapeutic index, and where increased bioavailabil- ity could lead to serious side effects. 40 September 2017 Tablets & Capsules Figure 1 Today's APIs are more complex a. Aspirin (approved 1900) b. Interferon (approved 2001) Figure 2 The BCS [4] Permeability Solubility Class II Low solubility High permeability Class I High solubility High permeability Class IV Low solubility Low permeability Class III High solubility Low permeability Table 1 Method of increasing API solubility [6] Class II Class III Class IV Nanoparticles Permeability enhancing excipients Solubility and permeability enhancing excipients Select more soluble polymorphs Efflux inhibitors Pro-drugs Liquid-filled capsules Pro-drugs Gastroretention Solid dispersions and solutions Add surfactant