Controlled delivery of apomorphine through buccal mucosa, towards a noninvasive administration method in Parkinson's disease: a preclinical mechanistic study.

  title={Controlled delivery of apomorphine through buccal mucosa, towards a noninvasive administration method in Parkinson's disease: a preclinical mechanistic study.},
  author={Constantin Itin and Rinat Komargodski and Abraham J. Domb and Amnon Hoffman},
  journal={Journal of pharmaceutical sciences},
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… 
Prolonged delivery of apomorphine through the buccal mucosa, towards a noninvasive sustained administration method in Parkinson's disease: in vivo investigations in pigs.
In the current work, prolonged systemic delivery of apomorphine via buccal mucosa was shown to be a promising treatment for Parkinson`s disease as a substitute for clinically utilized subcutaneous infusions and limitations of an Ussing diffusion chamber as an ex vivo research tool were discussed.
Types and evaluation of in vitro penetration models for buccal mucosal delivery
The characteristics of various in vitro penetration models of buccal mucosal delivery and the main factors affecting its application are analyzed, methods for evaluating mucosal integrity and viability are listed, and the characteristics and applicability of commonly used diffusion cells are summarized.
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Polymer films with 1% and 3% GLY concentrations are appropriate to be formulated for application on the buccal mucosa as a drug delivery system and investigations showed that GLY can reduce the mucoadhesivity and CTZ can increase the tensile strength of films.
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The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract.
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A case study of Cynapsus Therapeutics' APL-130277, a sublingual apomorphine formulation in clinical development for Parkinson's disease exemplifies the scientific, clinical and commercial considerations for systemic oral transmucosal drug delivery.
Ex vivo correlation of the permeability of metoprolol across human and porcine buccal mucosa.
Comparing the permeability of metoprolol and mannitol in ex vivo human and porcine buccal mucosa models at varying pH to validate whether the Porcine permeability model is predictive for human buCCal absorption suggests that buccAL mucosa from pigs can be used to predict humanbuccal absorption.
Pharmacokinetic-Pharmacodynamic Relationships of Apomorphine in Patients with Parkinson’s Disease
The population pharmacokinetic-pharmacodynamic data reflect the clinical observations of steep dose-effect curves if apomorphine is used in patients with random ‘on-off’ fluctuations and could be helpful in predicting the clinical effects of apomorphicine in the several subgroups of patients with Parkinson’s disease.
Modification of buccal drug delivery following pretreatment with skin penetration enhancers.
The effect of the lipophilic skin penetration enhancers octisalate, padimate O, and Azone on in vitro buccal permeability was assessed using caffeine, estradiol, and triamcinolone acetonide as model permeants and results suggested that the reduction in flux caused by PO and AZ may have been due to enhanced E2 tissue retention.
In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs.
  • R. Holm, E. Meng-Lund, +5 authors J. Jacobsen
  • Chemistry, Medicine
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2013
A very clear level C in vitro in vivo correlation was obtained, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.
Subcutaneously administered apomorphine
Apomorphine is a non-narcotic morphine derivative that acts as a potent dopaminergic agonist and the complexities of apomorphine uptake, distribution, and clearance probably contribute to its variability of clinical actions.
Oromucosal drug delivery: Trends in in-vitro biopharmaceutical assessment of new chemical entities and formulations.
  • M. Brandl, A. Bauer-Brandl
  • Medicine, Computer Science
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2019
The aim of the current review is to make the scientific community dealing with oromucosal drug formulation development aware of the opportunities provided by non-cellular artificial membranes.
Critical evaluation of permeation enhancers for oral mucosal drug delivery
Background: Drug delivery via oral mucosa is an alternative method of systemic administration for various classes of therapeutic agents. Among the oral mucosae, buccal and sublingual mucosae are the
Effect of Drug Lipophilicity and Ionization on Permeability Across the Buccal Mucosa: A Technical Note
It was hypothesized that logD describes buccal permeation better than logP, the most widely used predictor for drug permeation, and the correlation of logP and logD with buCCal permeability was compared.