Paediatric drug development of ramipril: reformulation, in vitro and in vivo evaluation

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Abstract

Ramipril is used mainly for the treatment of hypertension and to reduce incidence of fatality following heart attacks in patients who develop indications of congestive heart failure. In the paediatric population it is used most commonly for the treatment of heart failure, hypertension in type 1 diabetes and diabetic nephropathy. Due to the lack of a suitable liquid formulation, the current study evaluates the development of a range of oral liquid formulations of ramipril along with their in vitro and in vivo absorption studies. Three different formulation development approaches were studied: solubilisation using acetic acid as a co-solvent, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) and suspension development using xanthan gum. Systematic optimisation of formulation parameters for the different strategies resulted in the development of products stable for twelve months at long term stability conditions. In vivo evaluation showed CMAX of 10.48 µg/mL for co-solvent, 13.04µg/ml for the suspension and 29.58µg/mL for the cyclodextrin based ramipril solution. Interestingly, both ramipril solution (co-solvent) and the suspension showed a TMAX of 2.5h, however, cyclodextrin based ramipril produced TMAX at 0.75h following administration. The results presented in this study provide translatable products for oral liquid ramipril which offer preferential paediatric use over existing alternatives.

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  • Paediatric drug development of ramipril

    Rights statement: This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Drug Targeting on 7/5/15, available online: http://wwww.tandfonline.com/10.3109/1061186X.2015.1036275

    Accepted author manuscript, 267 KB, PDF-document

Details

Original languageEnglish
Pages (from-to)854-863
Number of pages10
JournalJournal of Drug Targeting
Volume23
Issue number9
Early online date7 May 2015
DOIs
Publication statusPublished - 2015

Bibliographic note

This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Drug Targeting on 7/5/15, available online: http://wwww.tandfonline.com/10.3109/1061186X.2015.1036275 Funding: BBSRC (BB/H016716/1).

    Keywords

  • Caco2, liquid formulation, oral drug delivery, ramipril

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