Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)

Pallavi Pawar, Yifan Wang, Golshid Keyvan, Gerardo Callegari, Alberto Cuitino, Fernando Muzzio

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug concentration of 9% Acetaminophen, containing 90% lactose and 1% Magnesium Stearate, and at a target compression force of 24 kN. A model for predicting dissolution profiles was developed using a 34−1 fractional factorial experimental design built around this targeted condition. Four variables were included: API concentration (low, medium, high), blender speed (150 rpm, 200 rpm, 250 rpm), feed frame speed (20 rpm, 25 rpm, 30 rpm), compaction force (8KN, 16KN, 24KN). The tablets thus obtained were scanned at-line in transmission mode using Near IR spectroscopy. The dissolution profiles were described using two approaches, a model-independent “shape and level” method, and a model-dependent approach based on Weibull's model. Multivariate regression was built between the NIR scores as the predictor variables and the dissolution profile parameters as the response. The model successfully predicted the dissolution profiles of the individual tablets (similarity factor, f2 ∼72) manufactured at the targeted set point. This is a first ever published manuscript addressing RTRt for dissolution prediction in continuous manufacturing, a novel and state of art technique for tablet manufacturing.

Original languageEnglish (US)
Pages (from-to)96-107
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume512
Issue number1
DOIs
StatePublished - Oct 15 2016

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Continuous manufacturing
  • Dissolution prediction
  • Feeders
  • Near IR spectroscopy
  • Real time release
  • Tablets

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