Chronotherapeutic Film-Coated Pulsatile Drug Delivery System of Resveratrol for the Management of Rheumatoid Arthritis

Research Article

Abstract

Circadian fluctuations in inflammatory cytokine production exacerbate joint pain, stiffness, and clinical pathology during early morning hours in rheumatoid arthritis patients. Standard immediate-release drug formulations fail to provide targeted drug availability during these peak symptomatic windows. Synchronizing therapeutic drug delivery with biological rhythms offers a targeted approach to mitigate nocturnal inflammatory cascades. A chronotherapeutic pulsatile dosage form was developed using a polymer-coated tablet core containing resveratrol to achieve time-controlled release after a predetermined delay period. Preformulation characterization confirmed the lipophilic nature (log P = 3.12 ± 0.05), melting point range (254 ± 0.62 °C), and spectroscopic absorption maximum (λ_max = 303 nm) of resveratrol. Fourier-transform infrared spectroscopy revealed no chemical interaction between the drug and formulation excipients. Core tablets prepared via direct compression were evaluated for mechanical integrity, mass variation, friability, and disintegration time. The optimized core tablet (F4) exhibited superior mechanical strength (4.1 ± 0.3 kg/cm²), acceptable friability (0.91%), and rapid core disintegration. Application of a hydrophobic film coating comprising ethyl cellulose (95%) and dibutyl phthalate (5%) established a functional polymeric barrier that delayed initial fluid ingress. Coated tablets displayed enhanced hardness (5.2 ± 0.3 kg/cm²), low friability (0.57%), and an extended disintegration lag phase (31.2 ± 0.9 min). In-vitro dissolution showed a defined lag period followed by rapid drug release, attaining 88.4% cumulative release within 60 minutes. The system successfully delays drug release while providing targeted anti-inflammatory action aligned with early morning arthritic exacerbations