title: Design, Synthesis and In Vitro Release Studies of Co-Drugs for Rheumatoid Arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammation that may affect many tissues and organs, but principally the synovial joints. The tendency for joint destruction is greatest in the early stages of disease hence current trend is to introduce a disease-modifying anti-rheumatic drug (DMARD) immediately after the diagnosis of RA in a step- up approach which is generally followed by its combination with a corticosteroid or NSAID.
  
  
  OBJECTIVE
  Hydroxychloroquine (HCQ) is a slow acting DMARD used in the early stage of RA. NSAIDs if given in combination with HCQ would provide immediate symptomatic relief from pain and inflammation even before HCQ starts showing its disease modifying effects. Long half life of HCQ results in its accumulation in the body while frequent intake of NSAIDs results in severe GI side effects. Present project aims at minimizing these shortcomings by designing co-drugs of HCQ and NSAIDs as a potential combination RA therapy.
  
  
  METHODS
  Synthesis of two co-drugs was achieved by CDI coupling, followed by their spectral characterization. In vitro release kinetics was studied by HPTLC in aqueous buffers and tissue homogenates of upper GIT.
  
  
  RESULTS
  Prodrugs were resistant to hydrolysis in buffers (pH 1.2 and 7.4) and stomach homogenates of Wistar rat but 32- 65% hydrolysis was observed in small intestinal homogenates.
  
  
  CONCLUSIONS
  We propose that the mutual prodrug strategy of a DMARD with NSAID could be useful in initial management of RA wherein NSAIDs would produce their anti-inflammatory effect and simultaneously the process of joint reconstruction by hydroxychloroquine could be initiated.
authors.forename: Patil
authors.initials: P
authors.lastname: Kashmira
authors.affiliation: Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune-411038, Maharashtra, India. suneeladhaneshwar@rediffmail.com.
authors.forename: Suneela
authors.initials: S
authors.lastname: Dhaneshwar
authors.forename: Chopade
authors.initials: C
authors.lastname: Shakuntala
authors.forename: Joshi
authors.initials: J
authors.lastname: Poorvashree
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015195:Drug Design; D004359:Drug Therapy, Combination; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006886:Hydroxychloroquine / Q000737:chemistry / Q000627:therapeutic use*; D007052:Ibuprofen / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D066298:In Vitro Techniques; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014020:Tissue Extracts
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D011355:Prodrugs; D014020:Tissue Extracts; D006886:Hydroxychloroquine; D007052:Ibuprofen