Assessment of the Water Sorption Capacity of Rifaximin Using the Dynamic Vapor Sorption Technique for Optimization of the Choice of Excipients and the Manufacturing Environment of Rifaximin Tablets.

Abstract

Background: Rifaximin, a medication of the rifamycin family with two distinct strengths of 200 mg and 550 mg in tablet form, is useful for the treatment of travelers' diarrhea. It has a solid yellow hue and is very hygroscopic in nature. It exhibits a variety of polymorphic forms such as α, β, γ, δ, and ε depending on bonded moisture. These polymorphs' varying chemical and physical characteristics, such as solubility and water content, may have a big impact on in vivo absorption, which in turn affects efficacy and safety. Therefore, understanding the polymorphic stability of rifaximin is crucial for formulating rifaximin tablets.

Objective: The current effort focuses on the understanding of water vapor sorption properties to control the polymorphic stability of rifaximin in the tablet formulation using the appropriate selection of excipients and manufacturing process.

Methods: The dynamic vapor sorption method in the range of 0-90% relative humidity at 25°C is used for understanding the sorption properties of drug substances and drug excipient mixtures; the state-of-the-art techniques of the X-ray diffraction method are used to identify polymorph conversions; and dissolution procedures are used for in vitro correlation studies.

Results: The sorption study data reveals that rifaximin is highly unstable at relative humidity conditions above 36%. When using excipients that have a low tendency to adsorb water in the formulation, the polymorphic results do not show any change in their intended form, and the in vitro dissolution data show an equivalency with the reference drug product.

Conclusion: The study prompted a successful outcome-oriented development of the formulation processing environment conditions design to develop a test formulation that has adequate polymorphic stability and also similarity in in-vitro dissolution profiles, with the reference product with highest similarity.

Highlights: The overall study described here is useful for swiftly gaining insight into the sorption characteristics of rifaximin, and it contributes to the widespread acceptance of rifaximin tablets as a treatment option.