pH-responsive dual pulse multiparticulate dosage form for treatment of rheumatoid arthritis

Drug Dev Ind Pharm. 2010 Nov;36(11):1295-302. doi: 10.3109/03639041003786185.


Background: Dual pulse multiparticulate systems may provide relief from circadian disorder rheumatoid arthritis.

Aim: The aim of this study was to develop a pH-responsive dual pulse multiparticulate dosage form containing a model drug ketoprofen, a nonsteroidal anti-inflammatory drug used for rheumatoid arthritis.

Method: The pellets were prepared by using extrusion-spheronization method and the core pellets were coated with a pH-sensitive poly(methyl) acrylate copolymer (Eudragit® L100-55, Eudragit® S100) to achieve site-specific drug release with a lag time. The formulated pellets were characterized for shape and size uniformity, friability, surface morphology studies, coating uniformity, and drug-excipient compatibility studies. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets.

Results: The particle size of core and polymer-coated pellets was found to be in the range of 0.95-1.3 and 1.42-1.61 mm, respectively. The pellets were spherical in shape with smooth texture and uniformity in size. The dual pulse was aimed at release after a lag time of 2 and 5 hours. In vitro dissolution tests were carried out for the first and second dose pellets in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The first dose release of the ketoprofen from the formulated pellets was established in pH 1.2 for a period of 2 hours, followed by pH 6.8. The second dose pellets were passed through pH 1.2, pH 6.8 followed by pH 7.5 for the rest of the study.

Conclusion: The study concluded that the formulated multiparticulate dosage form of ketoprofen was able to relieve circadian symptoms of rheumatoid arthritis during midnight and early morning.

MeSH terms

  • Acrylic Resins / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Arthritis, Rheumatoid / drug therapy
  • Delayed-Action Preparations
  • Drug Chronotherapy*
  • Excipients / chemistry*
  • Gastrointestinal Tract / metabolism
  • Hydrogen-Ion Concentration
  • Ketoprofen / administration & dosage*
  • Particle Size
  • Polymethacrylic Acids / chemistry
  • Pulse Therapy, Drug / methods
  • Solubility
  • Time Factors


  • Acrylic Resins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Eudragit L100-55
  • Excipients
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • Ketoprofen