Real-time assessment of critical quality attributes of a continuous granulation process

Abstract

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline -lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

Distribution of binder in granules produced by means of twin screw granulation

“…PVP was either added to the dry premix or dissolved in the granulation liquid (distilled water) Vercruysse et al, 2012). All granules were produced using the above mentioned ConsiGma™-25 production line, which has been described extensively elsewhere (Fonteyne et al, 2013a).…”

3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics

“…An alternative method is to incorporate drug into polymer filaments by hot-melt extrusion (HME), a widely used technique in the pharmaceutical industry, in which the raw materials are forced to mix in a rotating screw at elevated temperatures before being extruded through a die to produce a strand of uniform characteristics 10 . HME has been reported as a viable method to prepare a wide range of drug delivery systems, including fast or modified release solid dosage forms, granules, pellets, transdermal patches, transmucosal films and implants [11][12][13] . The use of HME to produce drug-loaded 3D printable filaments has been also shown to be achievable for water-soluble filaments to fabricate oral dosage forms 14 and for plastics used for medical devices 15 .…”

Process Analytical Technology for continuous manufacturing of solid-dosage forms

“…The influence of process parameters upon the solid state of theophylline (anhydrous or monohydrate) after twin-screw granulation was monitored with NIR and Raman spectroscopy [32]. Both spectroscopic techniques, with the help of multivariate data analysis, were capable of detecting even small unexpected solid-state changes.…”