Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms

Area of Science:

• Pharmaceutical Technology
• Enzyme Stabilization

Background:

• Pepsin is a crucial enzyme for digestion, but its activity can be compromised during pharmaceutical formulation.
• Solid dosage forms require specific manufacturing methods that may impact enzyme stability.

Purpose of the Study:

• To evaluate the impact of direct compression and wet granulation on pepsin activity.
• To determine optimal conditions for formulating solid dosage forms containing pepsin.
• To assess the influence of acids (tartaric and citric) on pepsin stability during formulation.

Main Methods:

• Modeled direct compression, considering heat and compression force effects on pure pepsin and pepsin-acid mixtures.
• Employed a factorial design to investigate wet granulation parameters (time, temperature, moisture) for pepsin and pepsin-acid mixtures.
• Analyzed pepsin activity post-formulation under various conditions.

Main Results:

• Direct compression is feasible for pepsin formulation, particularly at low compression forces and without acids.
• Wet granulation's impact on pepsin was minimal without acids, but temperature significantly affected activity when acids were present.
• Citric acid demonstrated a more detrimental effect on pepsin activity than tartaric acid during wet granulation.

Conclusions:

• Direct compression offers a viable method for pepsin solid dosage form preparation.
• Wet granulation can be used for pepsin processing under strictly controlled conditions, avoiding citric acid.
• Preformulation studies incorporating mathematical optimization are recommended for sensitive enzymes like pepsin.