The influence of polyamide 6,10 synthesis variables on the physicochemical characteristics and drug release kinetics from a monolithic tablet matrix

Oluwatoyin Ayotomilola Adeleke, Viness Pillay*, Yahya E. Choonara, Lisa C. Du Toit, Valence M.K. Ndesendo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

This study investigated the influence of solute-solvent quotients on the physicochemical properties and release kinetics of two amitryptyline-loaded polyamide 6,10 (PA 6,10) monolithic matrices, Formulations A and B (FA and FB). The molecular mass, crystallinity, structural elucidation and thermo-transitions were assessed using mass spectrophotometry, X-ray diffraction, FTIR and DSC. Surface morphologies of the matrices and physicomechanical strength were captured using SEM and textural analysis. Drug release, distension and matrix erosion were evaluated using mathematical modeling. FA and FB displayed overall drug release fractions of 0.58 and 0.92 with 55% and 30% of matrix remaining over 24 hours, respectively. The indentation diameters (FA = 1.51mm; FB = 2.39mm), deformation energies (FA = 0.02 J; FB = 0.03 J) and Brinell Hardness Numbers (FA = 17.88 N/mm2; FB = 14.45 N/mm2) were divergent. SEM revealed irregular matrix surfaces with varying pore distributions. Minimal shifts in the structural backbone of PA 6,10 and semi-crystallinity was noted. Multiple reversible and irreversible thermal transitions with molar masses of FA = 345.2g/mol and FB = 307.2g/mol were obtained. Drug release supported by in vivo studies provided sustained plasma levels of amitryptyline (Tmax = 24±0.5h and 12±0.5h; Cmax = 0.024±0.003μg/mL and 0.036±0.002μg/mL for FA and FB, respectively) compared to a conventional formulation, Trepiline® (Tmax = 4±0.5h and Cmax = 0.05±0.002μg/mL). The physicochemical properties of both formulations were reversibly influenced by differences in the PA 6,10 solute-solvent quotient employed during development. © 2010 Informa Healthcare USA, Inc.
Original languageEnglish
Pages (from-to)595-612
Number of pages18
JournalPharmaceutical Development and Technology
Volume15
Issue number6
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

Keywords

  • Amitryptiline hydrochloride
  • Controlled release
  • In vivo plasma concentrations
  • Kinetic modeling
  • Large White pig model
  • Monolithic matrix
  • Physicochemical
  • Polyamide 6,10
  • Solute-solvent quotients

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