High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Poorly soluble drugs present significant challenges in achieving effective oral bioavailability.
• Developing advanced drug delivery systems is crucial for improving therapeutic outcomes.
• Self-microemulsifying/micelle systems offer potential for enhancing solubility and absorption.

Purpose of the Study:

• To design a high drug loading formulation utilizing a self-microemulsifying/micelle system.
• To optimize the formulation for a poorly soluble model drug (CH5137291).
• To evaluate the impact of the novel formulation on drug absorption.

Main Methods:

• A high-throughput formulation screening (HTFS) system was employed for stepwise optimization.
• Selection involved drug solubility, surfactant screening (hydrophilic and lipophilic), and phase diagram analysis.
• Loading capacity, aqueous solubility, and oral absorption in Beagle dogs were assessed.

Main Results:

• An optimized formulation of d-α-tocopheryl polyoxyethylene 1000 succinate and PEG400 (8:2 ratio) achieved a high drug loading of 200 mg/mL.
• The formulation produced fine emulsions/micelles (49.1 nm) and maintained a supersaturated state effectively.
• Oral administration resulted in a 16.5-fold higher area under the plasma concentration-time curve compared to jet-milled formulations.

Conclusions:

• The developed high loading formulation significantly improves oral absorption of poorly soluble drugs.
• The HTFS system provides an efficient approach for designing advanced drug delivery systems.
• This strategy holds promise for enhancing the efficacy of challenging drug candidates.