Development of low-cost, weight-adjustable clofazimine mini-tablets for treatment of tuberculosis in pediatrics

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pediatric Pharmacology

Background:

• Clofazimine (CFZ) is crucial for treating multi-drug resistant tuberculosis (MDR-TB) but lacks suitable pediatric formulations.
• Current dosage forms limit dose adjustments for children, increasing risks of adverse events.

Purpose of the Study:

• To develop and characterize pediatric-friendly clofazimine mini-tablets.
• To evaluate the pharmacokinetic profile of the novel mini-tablets in rats compared to an oral suspension.

Main Methods:

• Micronized clofazimine powder was used to prepare mini-tablets via direct compression.
• Formulation optimization focused on achieving rapid disintegration and enhanced dissolution.
• Pharmacokinetic studies were conducted in Sprague-Dawley rats, comparing mini-tablets to an oral suspension.

Main Results:

• Optimized mini-tablets demonstrated rapid disintegration and maximized dissolution.
• Pharmacokinetic parameters (Cmax, AUC) showed no significant differences between formulations at the highest dose.
• Inter-animal variability precluded determination of bioequivalence per FDA guidelines.

Conclusions:

• A novel, low-cost clofazimine mini-tablet formulation suitable for pediatric use (from 6 months) was successfully developed.
• This formulation represents a significant advancement for oral clofazimine delivery in children requiring dose titration.
• Further studies are warranted to confirm bioequivalence and clinical efficacy in pediatric populations.