Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Alcohol-induced dose dumping is a critical issue for oral prolonged-release dosage forms, potentially leading to sub-therapeutic or toxic drug levels.
• Mucoadhesive prolonged-release tablets, like those containing quetiapine, require careful formulation to maintain consistent drug release profiles, especially under varying physiological conditions.

Purpose of the Study:

• To optimize the formulation of mucoadhesive quetiapine prolonged-release tablets (200 mg) to prevent alcohol-induced dose dumping.
• To investigate the effects of propylene glycol alginate (PGA), Eudragit RS PO (ERS), and coating on drug release in the presence and absence of ethanol.

Main Methods:

• Response surface methodology (RSM) was employed to optimize the independent variables: PGA, ERS, and coating.
• Formulations were evaluated for in vitro drug release in 0.1 N hydrochloric acid, with and without 40% v/v ethanol.
• Dissolution at 120 minutes (R1 without alcohol, R2 with alcohol) was measured and statistically analyzed using regression equations.

Main Results:

• Propylene glycol alginate (PGA) alone showed dose dumping in ethanol-containing media.
• Eudragit RS PO (ERS) addition provided structural support, reducing PGA erosion and mitigating dose dumping in ethanol.
• Four formulations met the target dissolution profile (30-40% at 120 min) in both conditions; ReadiLycoat further improved resistance to alcohol-induced dose dumping.

Conclusions:

• Optimized formulations demonstrated significant resistance to alcohol-induced dose dumping.
• Response surface methodology proved effective in optimizing the formulation and predicting drug release behavior.
• The combination of specific polymer concentrations and coating is crucial for developing robust prolonged-release systems resistant to ethanol challenges.