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Improved therapeutic potential of tapentadol employing cationic exchange resins as carriers in neuropathic pain: evidence from pharmacokinetic and pharmacodynamics study.

Abstract：

:Current investigation was endeavoured to overcome problem of poor palatability and bioavailability of centrally acting analgesic, tapentadol (TAP) by formulating controlled release drug-resin complexes (DRCs). The technology encompassed in preparation of DRCs involved chemisorption of TAP to weak cationic resins (KyronT-134 and Tulsion335) by batch method. Various formulation variables like drug-resin ratio, pH, resin activation and swelling time were optimized to achieve maximum drug loading in DRCs. FT-IR, DSC, pXRD, in vitro release study under bio-relevant condition of mouth and in vivo sensory taste evaluation established formation of taste masked DRC whereas dissolution study assured prolonged drug release behaviour of optimized DRC. Among DRCs, TAP-KyronT-134 complex exhibited higher drug loading (80.89 ± 4.56%), stability and prolonged release profile (10 h) without any detectable amount of drug release under salivary conditions. Pharmacokinetic studies in wistar rats revealed increased Tmax (2.67-fold), MRT (1.94-fold), elimination half-life (2.79-fold) and relative oral bioavailability (2.62-fold) of TAP on oral administration of optimized formulation compared to TAP solution. Furthermore, pharmacodynamics study confessed higher potential of DRC in attenuating chronic injury induced tactile allodynia for prolonged duration. In conclusion, the method developed is easily scalable and holds potential for commercialization with an evidence of obtaining more efficacious neuropathic pain management therapy.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sharma M,Soni R

doi

10.1038/s41598-018-21214-2

subject

Has Abstract

pub_date

2018-02-12 00:00:00

pages

2812

issue

1

issn

2045-2322

pii

10.1038/s41598-018-21214-2

journal_volume

8

pub_type

杂志文章

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