The present work aimed to form hydrophobic ion pairs
(HIPs) of
a small molecule remaining inside the oily droplets of SEDDS to a
high extent. HIPs of ethacridine and various surfactants classified
by functional groups of phosphates, sulfates, and sulfonates were
formed and precipitation efficiency, log D
n‑octanol/water, and solubility in different excipients
were investigated. Most lipophilic HIPs were incorporated into SEDDS
and evaluated regarding drug release. Docusate HIPs showed the highest
increase in lipophilicity with a precipitation efficiency of 100%,
a log D
n‑octanol/water of
2.66 and a solubility of 132 mg/mL in n-octanol,
123 mg/mL in oleyl alcohol, and 40 mg/mL in medium chain triglycerides.
Docusate HIPs were incorporated into three SEDDS of increasing lipophilicity
(F1 < F2 < F3) based on medium chain triglycerides, oleyl alcohol,
Kolliphor EL, and Tween 80 (F1: 1 + 5 + 2 + 2; F2: 3 + 3 + 2 + 2;
F3: 5 + 1 + 4 + 0). Highest achievable payloads ranged from 74.49
mg/mL (F3) to 97.13 mg/mL (F1) and log DSEDDS/RM increased by at least 7.5 units (4.99, F1). Drug release studies
via the diffusion membrane method confirmed minor release of docusate
HIPs from all SEDDS (<2.7% within 4 h). In conclusion, highly lipophilic
HIPs remain inside the oily phase of SEDDS and likely reach the absorption
membrane in intact form.
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