Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson's disease: physical characterization and ex vivo drug permeation through buccal mucosa

Drug Dev Ind Pharm. 2017 Nov;43(11):1836-1845. doi: 10.1080/03639045.2017.1349785. Epub 2017 Jul 12.

Abstract

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson's disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6 h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson's disease.

Keywords: Buccal tablets; controlled release; direct compression; hydroxypropyl methyl cellulose; mucoadhesion; piribedil.

MeSH terms

  • Acrylic Resins / chemistry*
  • Adhesiveness
  • Administration, Buccal
  • Animals
  • Calorimetry, Differential Scanning / methods*
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Hypromellose Derivatives / chemistry*
  • Mouth Mucosa / chemistry*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology*
  • Piribedil / administration & dosage*
  • Piribedil / chemistry
  • Piribedil / metabolism*
  • Sheep
  • Tablets / chemistry*

Substances

  • Acrylic Resins
  • Delayed-Action Preparations
  • Tablets
  • carbomer
  • Hypromellose Derivatives
  • Piribedil