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.
Highlights
Neuropathic pain is one of major healthcare disorder[1]
Literature reports various pharmaceutical grades of Polacrilex exhibit the property of taste masking, controlling release and improving stability by forming drug resin complexes (DRCs)
Taste masking of the TAP HCl was successfully achieved by preparing DRC using ion exchange resin in batch process
Summary
Neuropathic pain is one of major healthcare disorder[1]. Persistent burning or shooting neuropathic pain arises due to direct or indirect injuries to somatosensory system that impairs working efficiency and quality of social life of sufferers. Since chewing, crushing, dissolving or dose adjustment by dividing tablets for patients with hepatic or renal impairment results in dose dumping leading to overdose and toxicity[16,17] This necessitates for development of novel formulation approaches for improving the bioavailability and swallowability of TAP. The unique characteristic features of IERs like non-toxicity, non-irritancy, excreted unchanged from body, cost effectiveness and user friendly establishes them as suitable carrier system in drug delivery[18,19] They serve as molecular sieves for drugs. Both resins are insoluble in all solvents as well as not absorbed inside body and excreted unchanged These resins are commonly utilized as taste masking and stabilizing agents for bitter cationic drugs by forming drug resin complexes which remain stable in mouth[22,23]. Extended release resinates can maintain steady plasma drug levels, reduce frequency of multiple dosing, allows dose adjustment according to patient need and enhance adherence of patients to therapy[18,20]
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