Development and validation of a discriminatory dissolution method for rifaximin products.

The commercial product of rifaximin (RFX) contains α form. The α form can change to β form on exposure to high humidity that can occur during manufacturing, stability and/or in-use period. It is critical to maintain α form of the drug in a drug product to avoid variability in clinical response. FDA dissolution method was found to be non-discriminatory for RFX formulations containing either 100 % α or β form. The objective of the study was to develop a discriminatory dissolution method that can detect low levels of α to β transformation in RFX products. Formulations containing a variable fraction of α and β forms were prepared by direct compression method. Dissolution parameters investigated were type of dissolution medium (water and phosphate buffer), volume (500, 900 and 1000 mL) and paddle speed (50, 75 and 150 rpm). Dissolution in water with 0.2% sodium lauryl sulfate (SLS) was less than 80% and non-discriminatory. However, dissolution tested in phosphate buffer pH 7.4 with 0.2% SLS at 50 rpm was discriminatory with more than 17.5% difference in dissolution profile between formulations containing α and β form. The developed method can detect polymorphic transformation if there is 25% or more β form conversion.