Use of Quality by Design (QbD) Approach in Orodispersible Tablet Formulation of Fidaxomicin

Abstract

The aim behind development of 200 mg Fidaxomicin formulation is to provide cost-effective and innocuous formulation for the pediatric population using Quality by design (QbD) approach to enhance stability and bioavailability. The formulation, comprising fidaxomicin and excipients like microcrystalline cellulose and croscarmellose sodium, was designed for rapid disintegration and high absorption in the gastrointestinal tract, improving efficacy in neonates. Multiple risk factors like physical stability of dispersion system and oral bioavailability are taken into consideration while developing this suspension using orodispersible tablet formulation. The QbD methodology defined critical quality attributes (CQAs) such as dissolution, microbial limits, and content uniformity, ensuring consistent performance while conducting the quantitative and qualitative studies on three batches. Taste optimization with artificial chocolate flavor enhanced pediatric acceptability. Dissolution studies showed over 92% release within 5 minutes, and compatibility studies verified excipient stability. The manufacturing process, utilizing dry granulation and compression, achieved robust tablet characteristics. Stability studies confirmed a 36-month shelf-life at 30°C, with no significant degradation in various vehicles. This orodispersible tablet offers dosing flexibility, preservative-free composition, and a favorable safety profile, addressing unmet needs in pediatric Clostridium difficile infection (CDI) treatment with improved bioavailability and patient compliance, supported by a comprehensive control strategy for quality assurance.