*Five Years Citation in Google scholar (2016 - 2020) is. 1451*   *    IJPR IS INDEXED IN ELSEVIER EMBASE & EBSCO *       

logo

INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH

A Step Towards Excellence
Published by : Advanced Scientific Research
ISSN
0975-2366
Current Issue
Article In Press
No Data found.
ADOBE READER

(Require Adobe Acrobat Reader to open, If you don't have Adobe Acrobat Reader)

Index Page 1
Click here to Download
IJPR 9[3] July - September 2017 Special Issue

July - September 9[3] 2017

Click to download
 

Article Detail

Label
Label
Exploring self- immolative prodrugs of hydroxychloroquine with aryl propionic acid NSAIDs for dual drug release in rheumatoid arthritis: Synthesis and pharmacokinetics

Author: SUNEELA DHANESHWAR, POORVASHREE JOSHI
Abstract: Incomplete absorption and poor oral bioavailability of hydroxychloroquine (HCQ) as well as gastrointestinal erosions of NSAIDs have attributed to major hurdles in the treatment of rheumatoid arthritis. To overcome these hurdles, we designed self- immolative dual delivery approach for disease modifying antirheumatic hydroxychloroquine and propionic acid derivatives of NSAIDs. Here, we report synthesis, stability, bio-conversion and pharmacokinetics of hydroxychloroquine esters with flurbiprofen (HF), zaltoprofen (HZ) and ketoprofen (HK). Chemical tethering was accomplished by CDI coupling. Characteristic C=O stretch of newly formed ester in IR, absence of singlet of HCQ–OH in NMR, molecular ion peaks of desired molecular weights in mass spectra, accurate percentage of C, H, N analysis in elemental analysis confirmed synthesis of projected structures. Bulky NSAIDs imparted higher lipophilicity. Stability of prodrugs in acidic pH (1.2) and stomach environment supported the reported mechanism of inhibition of gastrointestinal disturbances to minimize local gastrointestinal irritation. Our study elucidated pH (7.4) and intestinal esterases responsive hydrolysis of prodrugs. In vivo pharmacokinetic studies proved improvement in oral absorption (75-84%) and pharmacokinetic parameters like C max, T max, and AUC0-24 than parent HCQ. So, overall pharmacokinetics data implies that these self-immolative prodrugs can be ideal alternatives for extended release of HCQ and NSAIDs for management of RA. Extensive pre- clinical studies are underway to establish their utility in RA.
Keyword: Prodrugs; Hydroxychloroquine; NSAIDs; Arthritis; Disease modifying agent; CDI coupling, Absorption
Download: Request For Article
 




ONLINE SUBMISSION
USER LOGIN


Username
Password
Login | Register
News & Events
SCImago Journal & Country Rank

Terms and Conditions
Disclaimer
Refund Policy
Instrucations for Subscribers
Privacy Policy

Copyrights Form

0.12
2018CiteScore
 
8th percentile
Powered by  Scopus
Google Scholar

hit counters free