Development and Validation of a Discriminatory Dissolution Method for Rifaximin Products

Area of Science:

• Pharmaceutical Sciences
• Drug Product Development
• Solid-State Chemistry

Background:

• Rifaximin (RFX) exists in polymorphic forms, primarily α and β.
• The α form is preferred for consistent clinical efficacy.
• Polymorphic transformation to the β form can occur due to environmental factors like humidity, impacting drug performance.

Purpose of the Study:

• To develop a dissolution method that can discriminate between different polymorphic forms of rifaximin (RFX).
• To establish a quality control method capable of detecting low levels of α to β polymorphic transformation in RFX drug products.

Main Methods:

• Preparation of RFX formulations with varying ratios of α and β polymorphs using direct compression.
• Evaluation of dissolution parameters including medium composition (water, phosphate buffer pH 7.4), volume (500-1000 mL), and paddle speed (50-150 rpm).
• Comparison of dissolution profiles between polymorphic forms using a U.S. Food and Drug Administration (FDA)-accepted method and the newly developed method.

Main Results:

• The standard FDA dissolution method was found to be non-discriminatory for RFX polymorphs.
• A discriminatory dissolution method was successfully developed using phosphate buffer (pH 7.4) with 0.2% sodium lauryl sulfate at a paddle speed of 50 rpm.
• This method demonstrated a significant difference (>17.5%) in dissolution profiles between α and β forms.
• The developed method can detect polymorphic transformation with 25% or more conversion to the β form.

Conclusions:

• A novel, discriminatory dissolution method for rifaximin (RFX) was established.
• This method is crucial for ensuring the quality and consistency of RFX drug products by monitoring polymorphic integrity.
• The method provides a reliable tool to prevent variability in clinical response associated with rifaximin polymorphic transformation.