Buccal delivery of Methimazole as an alternative means to optimize drug bioavailability: permeation studies and matrix system design

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Abstract

The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068 mg cm-2 h-1 and Kp = 0.065 cm h-1). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70% w/w) using Eudragit® RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provides optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.
Lingua originaleEnglish
pagine (da-a)5405-5410
Numero di pagine6
RivistaCurrent Pharmaceutical Design
Volume18
Stato di pubblicazionePublished - 2012

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Methimazole
Cheek
Biological Availability
Tablets
Mouth Mucosa
Pharmaceutical Preparations
Saliva
Swine
Dosage Forms
Hyperthyroidism
Glycerol
Permeability
Buffers
Mucous Membrane
Membranes

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Pharmacology

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title = "Buccal delivery of Methimazole as an alternative means to optimize drug bioavailability: permeation studies and matrix system design",
abstract = "The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068 mg cm-2 h-1 and Kp = 0.065 cm h-1). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70{\%} w/w) using Eudragit{\circledR} RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provides optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.",
keywords = "Methimazole; Hyperthyroidism; Transbuccal permeation; Porcine buccal mucosa; Eudragit{\circledR} RS 100; Buccal tablets",
author = "Giannola, {Libero Italo} and {De Caro}, Viviana and Giulia Giandalia and Siragusa, {Maria Gabriella}",
year = "2012",
language = "English",
volume = "18",
pages = "5405--5410",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",

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T1 - Buccal delivery of Methimazole as an alternative means to optimize drug bioavailability: permeation studies and matrix system design

AU - Giannola, Libero Italo

AU - De Caro, Viviana

AU - Giandalia, Giulia

AU - Siragusa, Maria Gabriella

PY - 2012

Y1 - 2012

N2 - The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068 mg cm-2 h-1 and Kp = 0.065 cm h-1). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70% w/w) using Eudragit® RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provides optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.

AB - The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068 mg cm-2 h-1 and Kp = 0.065 cm h-1). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70% w/w) using Eudragit® RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provides optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.

KW - Methimazole; Hyperthyroidism; Transbuccal permeation; Porcine buccal mucosa; Eudragit® RS 100; Buccal tablets

UR - http://hdl.handle.net/10447/78350

M3 - Article

VL - 18

SP - 5405

EP - 5410

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

ER -