Biopharmaceutical Process of Diclofenac Multi-particulate Systems for Chronotherapy of Rheumatoid Arthritis

Turkish Journal of Pharmaceutical Sciences

article

Sowjanya BATTU¹  Prasanna Raju YALAVARTHI²  Subba REDDY GV³  Saradha RADHAKRISHNAN¹  Ram Mohan Reddy THUMMALURU¹  Abbulu KONDE¹ 

[1] CMR College of Pharmacy, Department of Pharmaceutics;Sri Padmavathi School of Pharmacy, Division of Pharmaceutics;JNTUA College of Engineering, Department of Chemistry

关键词: Chronomodulation;    circadian;    fluidized bed;    hydrophilic carrier;    NSAID;    Wurster process;   

DOI  :  10.4274/tjps.92400

来源: Galenos Yayinevi

【 摘 要 】

Objectives: Diclofenac exhibits limited solubility, low bioabsorption and gastric toxicity. The objective of the study was to address the above limitations and to design a multi-particulate formulation for the chronotherapy of RA. Materials and Methods: Solid dispersions of DC with SSG and GG were prepared. Uniform-sized (∼400 µm) non-pareil seeds were coated with solid dispersions to produce immediate-release pellets (DMP-1 and DMP-2) and controlled-release pellets (DMP-3 and DMP-4). The resultant controlled-release pellets were further layered with methacrylate polymers to obtain pulsatile-release pellets (DMPP). Solubility, FTIR, DSC, micrometrics, SEM, drug content, drug release, pharmacokinetics, and stability studies were performed for DMPP. Results: The solubility of DC was improved by 164-folds due to the presence of hydrophilic carriers in the solid dispersions. No chemical and physical interactions were noticed in FTIR spectra and also in thermograms. A fluidized bed processor facilitated the production of high-quality, circular, and regular pellets with an angle of repose less than 19.5 degrees and DC content between 95.18% and 98.87%. The maximum drug was released from DMPP at the end of 12 hours. DMP-1 and DMP-2 pellets had 2 hr of drug release and pulsatile, controlled-release pellets had a 6 hr lag phase followed by 12 hr controlled release. Both DMP-1 and DMP-2–immediate showed first-order release followed by Hixson-Crowell kinetics, whereas DMPP pellets followed zero-order release with Higuchi’s kinetics. The maximum concentration of DC in plasma was 400.8 ng/mL at 5 hr for DMP-2 and 381.1 ng/mL at 14 hr for DMPP-5. The solubility of DC was increased with the application of solid dispersion and in turn increased the pharmacokinetics. The pellets were plausibly stable over a period of 90 days. Conclusion: Thus, multi-particulate pulsatile systems of DC were as effective as chronotherapeutics in the treatment of circadian rhythm-based ailments such as RA.

【 授权许可】

Unknown