pH-responsive dual pulse multiparticulate dosage form for treatment of rheumatoid arthritis.
BACKGROUND
Dual pulse multiparticulate systems may provide relief from circadian disorder rheumatoid arthritis.


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Lotlikar
Vishwanath
V
Bharati Vidyapeeth's College of Pharmacy, University of Mumbai, CBD Belapur, Navi Mumbai, India. vishwanath000@gmail.com
Kedar
Uttam
U
Shidhaye
Supriya
S
Kadam
Vilasrao
V
D000180:Acrylic Resins / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003692:Delayed-Action Preparations; D055870:Drug Chronotherapy; D005079:Excipients / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007660:Ketoprofen / Q000008:administration & dosage*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry; D020551:Pulse Therapy, Drug / Q000379:methods; D012995:Solubility; D013997:Time Factors
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D007660:Ketoprofen