Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level...

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Natural lipophilic and volatile compounds like thymol show potential for treating intestinal mucosa.
• Processing these substances for effective delivery presents significant challenges.

Purpose of the Study:

• To rationally design enteric pellets for thymol delivery using a self-emulsifying system (SES).
• To investigate the structural properties and release characteristics of the formulated pellets.
• To evaluate the potential of the formulation for treating intestinal diseases.

Main Methods:

• Utilized solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for rational design.
• Prepared thymol self-emulsifying system (SES) and enteric pellets (W90) via extrusion/spheronisation (M1-M3).
• Coated pellets with Eudragit®L for targeted release and performed ex vivo mucosal permeation studies.

Main Results:

• SES formed stable o/w emulsions (1-7 µm); ex vivo studies confirmed mucosal permeation and enterocyte delivery.
• Pellets (705-740 µm) exhibited low porosity and high density with similar thymol release profiles.
• Shorter process times increased thymol content; Eudragit®L coating prevented premature release in stomach conditions (<10%).
• ss-NMR revealed structural differences related to system stability and internal interactions.

Conclusions:

• The developed formulation and methodology are effective for delivering lipophilic volatile compounds like thymol to the intestinal mucosa.
• This approach shows promise for the development of novel treatments for intestinal diseases.