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Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
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Tip loaded cyclodextrin-carvedilol complexes microarray patches.

Qonita Kurnia Anjani1, Akmal Hidayat Bin Sabri2, Khuriah Abdul Hamid3

  • 1School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Fakultas Farmasi, Universitas Megarezky, Jl. Antang Raya No. 43, Makassar 90234, Indonesia.

Carbohydrate Polymers
|September 2, 2023
PubMed
Summary
This summary is machine-generated.

This study developed dissolving microneedle patches (MAPs) for transdermal delivery of carvedilol, a heart failure drug. These MAPs improve drug bioavailability and offer a promising alternative to oral administration.

Keywords:
CarvedilolCyclodextrinHeart failureMicroarray patchesTernary inclusion complexes

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Area of Science:

  • Pharmaceutical Sciences
  • Biomaterials Engineering

Background:

  • Carvedilol, a beta-blocker for heart failure, has poor oral bioavailability due to rapid metabolism.
  • Current oral delivery methods face challenges with efficacy and patient compliance.

Purpose of the Study:

  • To develop and evaluate novel dissolving microneedle patches (MAPs) for enhanced transdermal delivery of carvedilol.
  • To improve carvedilol bioavailability and provide sustained drug release for chronic heart failure management.

Main Methods:

  • Fabrication of MAPs using ternary cyclodextrin complexes of carvedilol with hydroxypropyl γ-cyclodextrin (HPγCD) and poly(vinyl pyrrolidone) (PVP).
  • Characterization of carvedilol-cyclodextrin complexes using DSC, XRD, NMR, and SEM.
  • Evaluation of MAPs' skin penetration, dissolution, biocompatibility, and in vivo pharmacokinetic performance in rats.

Main Results:

  • Ternary complex formation reduced carvedilol crystallinity, enhancing its suitability for MAPs.
  • MAPs successfully penetrated ex vivo porcine skin, with needles dissolving within 2 hours for transdermal delivery.
  • In vivo studies in rats showed significantly higher carvedilol AUC and sustained plasma levels compared to oral administration, with minimal toxicity.

Conclusions:

  • Carvedilol-loaded dissolving MAPs offer a viable strategy for improved transdermal drug delivery.
  • This novel approach has the potential to revolutionize chronic heart failure treatment by enhancing drug efficacy and patient experience.