Title:Design, Synthesis and In Vitro Release Studies of Co-Drugs for Rheumatoid Arthritis
Volume: 14
Issue: 1
Author(s): Patil Kashmira, Suneela Dhaneshwar, Chopade Shakuntala and Joshi Poorvashree
Affiliation:
Keywords:
Disease modifying anti-rheumatic drugs, inflammation, mutual prodrug, 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.
Method: 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.
Conclusion: 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.
