Gemfibrozil encapsulation and release from microspheres and macromolecular conjugates.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Gemfibrozil (Gem) is a lipid-regulating agent.
• Modifying drug release is crucial for therapeutic efficacy.
• Macromolecular conjugates and microspheres are potential drug delivery systems.

Purpose of the Study:

• To evaluate and compare macromolecular conjugates and microspheres for modifying gemfibrozil release.
• To investigate the impact of polymer type, molecular weight, and drug-polymer ratio on release profiles.

Main Methods:

• Covalent linkage of gemfibrozil to poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA).
• Preparation of microspheres via spray drying using chitosan, PHEA, PHPA, or (2-hydroxypropyl)methylcellulose (HPMC).
• Characterization of systems using scanning electron microscopy, particle size analysis, and in vitro dissolution testing.

Main Results:

• Microspheres consistently modulated gemfibrozil release.
• Optimal release modulation was achieved with low molecular weight chitosan microspheres combined with PHPA or HPMC at 2:1 or 3:1 polymer/drug ratios.
• PHEA-G conjugates released gemfibrozil rapidly (<2 hours), while PHPA-G conjugates exhibited sustained release over 10 hours.

Conclusions:

• Microsphere formulations offer a viable strategy for controlled gemfibrozil release.
• The choice of polymer and formulation method significantly impacts drug release kinetics.
• PHPA-G conjugates demonstrate potential for sustained-release applications.