Controlled Delivery of Apomorphine Through Buccal Mucosa, Towards a Noninvasive Administration Method in Parkinson's Disease: A Preclinical Mechanistic Study

Constantin Itin, Rinat Komargodski, Abraham J. Domb, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Apomorphine (APO), a potent treatment for Parkinson's disease, is only administered parenterally either as intermittent injections or as an infusion. This is due to extensive hepatic “first pass” metabolism. Prolonged delivery through buccal mucosa may be potential substitute for parenteral infusions. To investigate this concept of buccal mucosal delivery, permeability ex vivo studies were performed through excised porcine buccal mucosa by utilizing Ussing diffusion chamber. Permeability rates were assessed for APO from simulated saliva medium at pH 7.4 as well as with utilization of different permeability modifying methods. Lowering the pH to 5.9 decreased permeability rate six-fold, while addition of ethanol: propylene glycol solution elevated it four-fold. Addition of nano-scale lipospheres to the donor compartment delayed the accumulation of APO at the receiver side, prolongating the lag-time from one to approx. three hours. These findings were strengthened by results obtained with co-administration of permeability markers (standards) atenolol and metoprolol. Simulation of the obtained permeability rates to in vivo setup in human showed therapeutically relevant plasma levels when using the outcomes of the current study. These findings verify the novel concept of APO prolonged release buccal administration as a noninvasive substitute for parenteral infusions in treating Parkinson's disease.

Original languageAmerican English
Pages (from-to)2729-2734
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number9
DOIs
StatePublished - Sep 2020

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • Apomorphine
  • Buccal
  • Buccal delivery
  • Controlled delivery
  • Lipid nanoparticles
  • Paracellular transport
  • Permeation enhancer
  • Transcellular transport
  • Ussing diffusion chamber
  • pH

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