Control of API release with matrix polymorphism in tristearin microspheres

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Glycerides serve as crucial solid matrices in pharmaceutical formulations.
• Drug release mechanisms are often diffusion-based and influenced by lipid matrix properties.
• Triglyceride polymorphism significantly impacts drug release kinetics.

Purpose of the Study:

• To investigate the effect of tristearin polymorphic states (α and β) on caffeine drug release.
• To explore how conversion routes between polymorphs influence drug release.
• To understand the impact of API loading on drug release from lipid matrices.

Main Methods:

• Utilized model formulations of crystalline caffeine embedded in tristearin.
• Employed contact angle measurements to assess wettability.
• Applied NMR diffusometry to study diffusion-based drug release mechanisms.
• Analyzed the influence of different polymorphic conversion routes.

Main Results:

• Drug release from the α-polymorph is diffusion-limited, with initial burst release due to good wetting.
• The β-polymorph exhibits slower initial release due to poor wettability and surface blooming.
• The method of achieving the β-polymorph affects crystallite size and packing, altering release profiles.
• Increased API loading enhances porosity and accelerates drug release.

Conclusions:

• Triglyceride polymorphism is a critical factor controlling drug release rates in pharmaceutical formulations.
• Wettability, porosity, and tortuosity of lipid polymorphs dictate drug diffusion.
• Formulation strategies should consider polymorphic transitions and API loading for optimized drug delivery.