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Tablets & Capsules April 2020 37 eye on excipients This installment of "Eye on Excipients" provides some DOs and DON'Ts for developing successful SEDDS formula- tions to enhance API bioavailability. The self-emulsifying drug delivery system (SEDDS) is one of the most viable options for enhancing the bio- availability of poorly soluble active pharmaceutical ingredients (APIs). SEDDS consist of digestible compo- nents, so they can provide a prod- uct with optimized pharmacokinetic properties while minimizing variabil- ity and food effect. They maintain API solubility during gastrointesti- nal dilution and transit by processes that govern the digestion of dietary lipids. The enhanced bioavailabil- ity and performance of SEDDS for- mulations can also be attributed to increased intestinal absorption via supersaturation, tight junction mod- ulation, and reduced first-pass effect via lymphatic transport with long- chain fatty acid esters. SEDDS can be simple formula- tions to develop and process. A typ- ical formulation is composed of an oily vehicle (lipid), a surfactant, and a co-surfactant, or else a single excipient with self-emulsifying prop- erties. Depending on the formula- tion, SEDDS can be manufactured as either liquid-filled softgels or liq- uid-filled two-piece capsules. Developing a successful SEDDS formulation As shown in Figure 1, API solu- bility screening is the first step in developing a SEDDS formulation. Solubility is an indication of a for- mulation's expected drug load and performance. After obtaining solu- bility data at ambient conditions in a broad range of oily vehicles, sur- factants, and co-surfactants, you can select the best delivery vehicle based on the targeted dosage form (softgel or two-piece capsule) and the API's biopharmaceutics (such as efflux sys- tem and first-pass effect). Solubil- ity screening for SEDDS formula- Inayet Ellis Gattefossé USA Figure 1 SEDDS formulation development steps Determinations with API Decisions Determination without API Step 1 API solubility screening • API solubility limit in liquid and solid excipients • Excipient selection based on dose and type of dosage form • Eventual role of excipient in formulation and in vivo Step 3 In vitro lipolysis testing Formulation maintains the dose in solution (≥75% at 60 minutes) Step 2 Miscibility testing to rule out immiscible formula Single excipient Two or more excipients to solubilize the entire dose SEDDS formulation In vivo testing Pre-clinical study