title: A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication.
  
  
  OBJECTIVE
  The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA.
  
  
  METHODS
  A 3-factor, 3-level Box-Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats.
  
  
  RESULTS
  The particle size and encapsulation efficacy of these microspheres were 117.36 ± 10.54 µm and 85.06 ± 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation revealed delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund's adjuvant-induced arthritis rats.
  
  
  CONCLUSIONS
  The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy , AGI , Hyderabad , Telangana , India .|b School of Pharmaceutical Sciences and Technologies, JNTUK , Kakinada, Andhra Pradesh , India .
authors.forename: Krishna
authors.initials: K
authors.lastname: Sanka
authors.affiliation: c College of Pharmaceutical Sciences, Andhra University , Visakhapatnam, Andhra Pradesh , India , and.
authors.forename: Rajeswara Rao
authors.initials: RR
authors.lastname: Pragada
authors.affiliation: d College of Pharmacy, Palamuru University , Mahabubnagar , Telangana , India.
authors.forename: Prabhakar Reddy
authors.initials: PR
authors.lastname: Veerareddy
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002351:Carrageenan / Q000633:toxicity; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D008863:Microspheres; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013577:Syndrome
chemical_list: D018501:Antirheumatic Agents; D004008:Diclofenac; D002351:Carrageenan; C056498:aceclofenac
keywords: Aceclofenac; Box–Behnken design; colon delivery; delayed release; eudragit S-100