Login / Signup

Hydrophobic Ion Pairing of Small Molecules: How to Minimize Premature Drug Release from SEDDS and Reach the Absorption Membrane in Intact Form.

Helen SpleisChristoph FedererVictor ClausMatthias SandmeierAndreas Bernkop-Schnürch
Published in: ACS biomaterials science & engineering (2023)
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 D SEDDS/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.
Keyphrases
  • drug release
  • small molecule
  • drug delivery
  • ionic liquid
  • emergency department
  • mass spectrometry
  • protein protein
  • alcohol consumption
  • drug induced
  • electronic health record
  • adverse drug
  • case control