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In addition to those therapeutic uses of MCT, it can serve as an important primary solubilizing excipient in self-emulsifying nutraceutical delivery systems (SENDS). Other ingredients commonly used as solubilizers in SENDS include long-chain triglycerides and natural oils. As oil-in-water emulsions, SENDS enable formulators to deliver active nutraceutical ingredients (ANIs) composed of triglycerides and/or natural oils, mono- and di-glyceride emulsifiers, and surfactants. Like many of today's active pharmaceutical ingredients (APIs), a number ANIs exhibit poor aqueous solubility and thus poor bioavailability. Limited bioavailability, in turn, can restrict an ANI's therapeutic efficacy. By formu- lating a SENDS that delivers the ANI in the form of a highly dispersed micellar system, dissolution of the ANI can reach a molecular level that improves its overall solu- bility in the digestive system. That ultimately leads to greater absorption of the ANI and better bioavailability and therapeutic efficacy. Poorly water soluble ANIs include fat-soluble vitamins (A, D, E, and K), botanical actives (carotenoids like lycopene and ß-carotene), as well as other popular nutraceu- tical supplements, such as co-enzyme Q10 (CoQ10) and quercetin [4]. The practically insoluble nature of these ANIs makes them ideal candidates for a SENDS formulation. Typical components of a SENDS pre-concentrate Typically, a SENDS comprises the ANI dissolved in a combination of solubilizer, emulsifier, surfactant, and co-sur- factant. This mixture is referred to as the pre-concentrate. Solubilizers. These are typically fully esterified medium- or long-chain lipids that are manufactured by esterification of fatty acids to a substrate, typically glycerol or propylene glycol. The glycerides that result are highly lipophilic and can dissolve very hydrophobic ANIs. Emulsifiers. These are typically partially esterified lipids manufactured by the partial esterification of glyc- erol or propylene glycol with fatty acids. Depending on the fatty acid chain length and degree of esterification, these emulsifiers can be manufactured to generate differ- ent hydrophilic-to-lipophilic balances (HLBs). In certain cases—depending on the HLB of the ANI—a partially esterified lipid can serve as a primary solubilizer. Surfactants and co-surfactants. Manufacturing an opti- mal SENDS formulation—a stable, finely dispersed ANI- carrying oil-in-water emulsion—often requires high con- centrations (greater than 30 percent) of surfactants and co-surfactants. The most common types of surfactants and co-surfactants employed in SENDS formulations are pegylated esters, polyethoxylated sorbitan esters, and polyethoxylated glycerides. Pegylated esters are manufac- tured through the esterification of polyethylene glycol with respective fatty acids. Polyethoxylated castor oil is prepared by reacting ethylene oxide with castor oil, and polyethoxylated sorbitan esters are made through the esterification of polyethoxylated sorbitan with respective fatty acids after the cyclization of sorbitol. Formulating the pre-concentrate There are four general steps to formulating a SENDS pre-concentrate: • Select the pre-concentrate component candidates; • Determine the ANI's maximum solubility in the pre- concentrate component candidates; • Determine the emulsions' characteristics after dilut- ing the pre-concentrate in aqueous media; and • Assess the in vitro dissolution of the ANI from the pre-concentrate formulation. Select the pre-concentrate component candidates. First, determine the aqueous solubility, log P, melting point, and solubility parameter of the API. Typically, a log P greater than 4 indicates that a fully esterified lipid should be employed as the primary solubilizer [5]. By matching the HLB of the ANI to the HLB of the pro- posed SENDS components, one can select the SENDS pre-concentrate solublizers and emulsifiers to conduct additional studies on maximum solubility. 12 July 2017 Tablets & Capsules Figure 1 Solubility of CoQ10 in various excipients [7] Brij Caprol 90 Caprol PGMC Captex 200 Captex 355 Ethyl oleate Labrafac Lipofile WL 1349 Lauroglycol FCC Oleic acid Peccol Cremophor EL Cremophor RH 40 Solutol HS 15 Tween 20 Tween 80 Lauroglycol 90 Transcutol P 0 20 40 60 80 100 120 140 160 180 200 2.12 67.6 10.43 1.16 9.38 6.99 11.02 99.06 96.52 102.4 110.9 186.1 155.4 157.9 99.69 70.45 41.73 Solubility (mg/g)