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Tablets & Capsules May 2016 41 eye on emulsification of API in the lumen and possibly effect para-cellular transport; • The potential to reduce the P- glycoprotein mediate efflux of cer- tain APIs, improving bioavailability; • The reduction of fasted and fed pharmacokinetic differences of APIs; • APIs that can be readily digested and metabolized; • Formulations that can be easily filled into soft and hard capsules (gelatin or non-gelatin) for oral administrations; and • Higher-molecular-weight lipids that are solid at room temperature and have the potential to be readily incorporated into direct-compression tablets while still providing the advantages cited above. There are two basic approaches to formulating with functional lipids: dissolution of the API in a neat lipid or dissolution of the API in a SEDDS pre-concentrate. In the former, the API is simply dissolved in a lipid excipient and then filled into a soft or hard capsule. Once the capsule is ingested, the API-containing lipid is released and undergoes digestion through the actions of lipases. This results in the body creating an emul- sified system containing the API, lipid, bile salts, and phospholipids. The API remains in the solubilized state in the emulsion and is thus absorbed from the gastrointestinal (GI) tract. In the latter, a SEDDS pre-concentrate is developed by employing a combination of func- tional lipids, including any permuta- tion of the following: a primary solu- bilizer, a secondary surfactant/co- emulsifier, and a primary surfactant. The optimized pre-concentrate is filled into a soft or hard capsule for oral administration. Upon contact with GI fluid, the pre-concentrate forms an emulsion or micro-emul- sion, which carries the API until it is absorbed. Components of a stable SEDDS pre- concentrate Solubilizers. These are typically fully esterified lipids manufactured by the esterification of glycerol or propylene glycol with free fatty acids of varying chain lengths. These products are highly lipophilic and have no hydrophilic-lipophilic bal- ance (HLB). Secondary surfactants or co- emulsifiers. These are typically par- tially esterified lipids manufactured by the partial esterification of glyc- erol or propylene glycol with free fatty acids or oils (via a catalyst). These emulsifiers provide a range of HLB values according to their degree of esterification, fatty acid chain length, and saturation, and that allows you to select a suitable emulsi- fication system for specific APIs. For certain APIs with similar solubility parameters, an emulsifier can be employed as a solubilizer and used alone. Primary surfactants. The produc- tion of optimal SEDDS formulations often requires high concentrations (greater than 30 percent) of surfactant agents. There are many types of sur- factants that can be employed in the pre-concentrate to emulsify oil and water and even facilitate the forma- tion of nano-emulsions. The most common types employed for SEDDS John K. Tillotson Abitec excipients This edition of the column discusses using functional lipids and self-emulsifying drug delivery systems (SEDDS) to over- come the poor solubility and permeability of today's APIs. The majority of new chemical entities (NCEs) being evaluated for therapeutic use exhibit low solubility, low permeability, or both, indicating that they are BCS Class II, Class III, or Class IV compounds. There are numerous and varying strategies for improving the solubility of BCS Class II active pharmaceutical ingre- dients (APIs), including • Micronizing and nano-sizing them to increase the surface area; • Using solid dispersions and spray drying to hold the API in a higher energy state; • Adding surfactant to aid in dis- solution; • Adjusting micro-environmental pH; • Using organic salt conjugation to create more soluble ion pairs; and • Using flash precipitation. When it comes to improving the intrinsic permeability of APIs, there are even fewer options. Lipid-based formulations, however, offer a very safe and effective method of poten- tially improving both the solubility and permeability of APIs. The bene- fits of lipid-based formulations include: • A large increase in the solubility of BCS Class II APIs by incorporat- ing them into an oil-water emulsion; • The potential to greatly improve the permeability of polar APIs by means of stimulating bile salt secre- tion from lipolysis to improve the