Self-emulsifying drug delivery systems (SEDDS): How organic solvent release governs the fate of their cargo

Abstract

Organic solvents are commonly used in self-emulsifying drug delivery systems (SEDDS) to increase payloads of orally administered poorly soluble drugs. Since such solvents are released to a varying extent after emulsification, depending on their hydrophilic nature, they have a substantial impact on the cargo. To investigate this impact in detail, quercetin and curcumin as model drugs were incorporated in SEDDS comprising organic solvents (SEDDS-solvent) of logP < 2 and > 2. SEDDS were characterized regarding size, payload, emulsification time and solvent release. The effect of solvent release on the solubility of these drugs was determined. Preconcentrates of SEDDS-solvent_{logP < 2} emulsified more rapidly (< 1.5 min) forming smaller droplets than SEDDS-solvent_{logP > 2}. Although, SEDDS-solvent_{logP < 2} preconcentrates provided higher quercetin solubility than the latter, a more pronounced solvent release caused a more rapid quercetin precipitation after emulsification (1.5 versus 4 h). In contrast, the more lipophilic curcumin was not affected by solvent release at all. Particularly, SEDDS-solvent_{logP < 2} preconcentrates provided high drug payloads without showing precipitation after emulsification. According to these results, the fate of moderate lipophilic drugs such as quercetin is governed by the release of solvent, whereas more lipophilic drugs such as curcumin remain inside the oily phase of SEDDS even when the solvent is released.

Keywords: Bioavailability; Diffusion coefficient; Drug delivery; Drug release; Nanoemulsions; Taylor dispersion analysis (TDA).