Abstract

DETERMINATION OF RELATIVE POLYMORPHIC DISTRIBUTION BETWEEN VARIOUS POLYMORPHIC FORMS OF RIFAXIMIN DRUG IN RIFAXIMIN TABLETS USING POWDER X-RAY DIFFRACTION TECHNIQUE

Gorla S. Reddy and Chava V. N. Rao*

ABSTRACT

Rifaximin shows crystal polymorphism, and several polymorphs (α, β, γ, δ, ε) have been described. In vitro studies, it shows different dissolution and solubility rates for these polymorphs, and in vivo investigations in dogs found different PK patterns and polymorphs displaying the highest systemic bio-availability. There is a need to develop a sensitive method for the determination of relative polymorphic distribution of Rifaximin API in Rifaximin tablets. Powdered XRD is a preferred and extensively used technique for the determination of polymorphic mixtures, which has many advantages like uniqueness of X-ray powder pattern of the compounds, non-destructive nature, simplicity and measurement at room temperature of both the drug substance and product. To understand the polymorphic distribution in the sample a quantitative (%) XRD method was developed, wherein characteristic and specific peaks for each polymorph have been selected based on the XRD profile of individual polymorph and their distribution is estimated by the percentile calculation method. This PXRD method has its own advantage like minimum time interval, end user friendly, minimizes human errors and decreases sample preparation errors. In present study, PXRD method represents a convenient method to determine relative polymorphic distribution between various polymorphic forms of Rifaximin API in Rifaximin tablets. This method is capable in determining the amount of α, β, δ and ε polymorphs of Rifaximin API in Rifaximin tablets in single attempt. Validation of quantization method was carried out with respect to specificity, precision, ruggedness linearity, robustness, Limit of Detection (LOD) and Limit of Quantification (LOQ). This method also can be used in manufacturing site to check the relative polymorphic distribution between various polymorphs of Rifaximin API in Rifaximin Tablets.

Keywords: Rifaximin tablets, Polymorphs (?, ?, ? and ?), Powdered XRD, Validation, polymorphic distribution.