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

Abstract

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.

Keywords:

• Eudragit®
• extrusion–spheronization
• ketoprofen
• lag time
• multiple unit
• pulsatile release
• rheumatoid arthritis

Acknowledgments

The authors would like to thank Alkem Research Laboratories Ltd., Mumbai, India, for DSC study and Bombay Textile Research for SEM study and interpretation.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.