SYNTHESIS OF PIOGLITAZONE HYDROCHLORIDE OF PHARMACEUTICAL PURITY AT SMALL PLANT SCALE

Wiesław Pucko Jacek Roszczyński 1Jerzy Winiarski Piotr A. Baran 1Teresa Paszkowska-Reymer Andrzej Leś 2Marta Ławecka 1

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
2. Warsaw University, Faculty of Chemistry, Pasteura 1, Warszawa 02-093, Poland

Abstract

Pioglitazone hydrochloride (1) is an antidiabetic agent for the treatment of noninsulin dependent diabetes mellitus (NIDDM). It decreases hyperglycaemia and acts by increasing insulin sensitivity.

Reduction of
(E)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzylidene}thiazolidene-2,4-dione with sodium borohydride and cobalt(II) complex in dimethyldioxyme and a subsequent conversion of a free base with HCl afforded pioglitazone hydrochloride in high yield (about 95%) and purity (above 99%).

wz1.gif

The scale-up was performed taking into account the results of a laboratory study on the optimization of a key process of the synthesis, i.e. the reduction of the double bond in benzylidenethiazolidenedione [1,2].

A summary of the small plant scale synthetic procedure will be given. More details are available through the polish patent application No. P-376857 [3].


[1] A. Leś, W. Pucko, W. Szelejewski, "Optimisation of the reduction of 5-benzylidenethiazolidine-2,4-dione derivative supported by the reaction response surface analysis: synthesis of pioglitazone hydrochloride", Organic Process Research & Development, 8 (2004) 157-162.
[2]. A. Leś, W. Szelejewski, "Optymalizacja wybranych etapów syntez substancji farmaceutycznych", Przemysł Chemiczny, 84/5 (2005) 314-319
[3]. W. Pucko, J. Roszczyński, J. Winiarski, P. Baran, W. Szelejewski, A. Leś, M. Ławecka, "Sposób wytwarzania chlorowodorku pioglitazonu o wysokiej czystości farmaceutycznej", polskie zgłoszenie patentowe nr P-376857, dn. 01.09.2005.

Legal notice
  • Legal notice:

    Copyrighted materials, (c) Pielaszek Research, all rights reserved.
    The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced, stored in or introduced into a retrieval or caching system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), or for any purpose, without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
    In every case, proper references including Author(s) name(s) and URL of this webpage: http://science24.com/paper/6503 must be provided.

 

Related papers
  1. Bioequivalence study of ondansetron film-coated tablets in healthy volunteers
  2. Capecitabine molecular structure in the liquid state as predicted from NMR measurements and theoretical calculations.
  3. Preparation and physicochemical properties of crystalline forms and amorphous pemetrexed disodium
  4. Comparison of bisoprolol pharmacokinetics after 10 mg oral administration of Bisocard and reference formulation to healthy subjects
  5. Bioequivalence study of 500 mg cefuroxime film-coated tablets in healthy volunteers
  6. Efficient preparation of a key intermediate in the exemestane synthesis
  7. Optimization of BR-8 synthesis
  8. Opimisation of preparation of TZ-6
  9. A novel synthesis of 19-nor analogs of vitamin D
  10. The Concept of the Central Strategic Program - Innovative Medicines
  11. Application of confidence intervals to bioanalytical method validation
  12. Optimization of AR-3 synthesis
  13. Polimorphism of Active Pharmaceutical Ingredients
  14. CAN A QUEST FOR A NEW DRUG OF POLISH ORIGIN BE SUCCESSFUL?
  15. ROPINIROL - GENERIC DRUG FOR PARKINSON'S DISEASE
  16. THE VALIDATION OF ANALYTICAL METHODS OF A PHARMACEUTICAL ACTIVE SUBSTANCE PRODUCED IN SMALL SCALE PLANT (SSP). THE EXAMPLE OF PIOGLITAZONE HYDROCHLORIDE.
  17. NEW IMPROVED METHOD OF POLYMORPHIC α FORM OF IMATINIB MESYLATE (GLEEVEC®) SYNTHESIS.
  18. SYNTHESIS OF 25- HYDROXYVITAMIN D3 - CALCIFEDIOL FROM VITAMIN D2
  19. NEW SYNTHESIS OF 11-(1-PIPERAZINYL)- DIBENZO[b,f][1,4]THIAZEPINE, A CRUCIAL INTERMEDIATE IN QUETIAPINE PRODUCTION.

Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Wiesław Pucko
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-01-31 08:53
Revised:   2009-06-07 00:44
Google
 
Web science24.com
© 1998-2021 pielaszek research, all rights reserved Powered by the Conference Engine