Designing HPMC matrices with improved resistance to dissolved sugar

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• High sugar concentrations can accelerate in vitro drug release from hydroxypropyl methylcellulose (HPMC) matrices.
• Understanding formulation variables that influence this sucrose sensitivity is crucial for designing stable drug delivery systems.

Purpose of the Study:

• To investigate how common formulation variables modulate sucrose sensitivity in HPMC matrices.
• To explore the design of HPMC formulations with enhanced resistance to sugar-induced drug release acceleration.

Main Methods:

• Investigated drug release from 30% HPMC (Methocel™ K4M) matrices with various tablet diluents (lactose:microcrystalline cellulose, dextrose, d-xylose, microcrystalline cellulose) in 0.7M sucrose at 37°C.
• Evaluated the effect of HPMC particle size (<63μm) and viscosity (K100M, K100LV) on sugar resistance.
• Designed and tested a more resistant HPMC matrix in 0.9M sucrose.

Main Results:

• Lactose:microcrystalline cellulose mixtures, dextrose, and d-xylose as diluents resulted in rapid drug release (1-4h) due to matrix swelling and erosion.
• Microcrystalline cellulose as the sole diluent provided extended release for 10 hours.
• Small particle size and high/low viscosity HPMC improved resistance to sugar-induced release.
• A specifically designed HPMC matrix achieved extended release (>16h) in 0.9M sucrose.

Conclusions:

• Internal and external sugars can combine to disrupt the diffusion barrier properties of HPMC gel layers, accelerating drug release.
• Judicious selection of excipient properties, including diluent type, particle size, and HPMC viscosity, significantly improves the tolerance of HPMC matrices to high sucrose environments.
• This knowledge enables the development of robust HPMC-based extended-release formulations suitable for high-sugar conditions.