Microenvironmental pH modulation based release enhancement of a weakly basic drug from hydrophilic matrices

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Weakly basic drugs exhibit pH-dependent solubility, leading to poor release from sustained release formulations.
• Optimizing microenvironmental pH is crucial for enhancing drug release of such compounds.

Purpose of the Study:

• To quantitatively analyze the relationship between microenvironmental pH modulation and drug release enhancement.
• To investigate the impact of polymeric and nonpolymeric pH modulators on drug release from a trimethoprim-loaded matrix.

Main Methods:

• Utilized a prototype matrix system with trimethoprim (a weakly basic drug), hydroxypropyl methylcellulose (HPMC), and pH modulators (Eudragit L100-55, malic acid).
• Employed water uptake and scanning electron microscopy (SEM) to assess matrix properties.
• Correlated experimentally determined microenvironmental pH with percent drug release.

Main Results:

• Eudragit L100-55 showed limited release enhancement due to drug basicity, reduced water uptake, and matrix permeability.
• Malic acid significantly lowered microenvironmental pH, achieving pH-independent drug release.
• A strong linear correlation (R=0.83) was observed between microenvironmental pH and drug release.

Conclusions:

• Nonpolymeric pH modulators, like malic acid, are effective in enhancing drug release of weakly basic drugs.
• Drug diffusion across the gel barrier is the predominant release mechanism in these formulations.
• Microenvironmental pH control is a viable strategy for optimizing drug release from sustained release systems.