Simplified formulations with high drug loads for continuous twin-screw granulation

Meier, Robin; Thommes, Markus; Rasenack, Norbert; Krumme, Markus; Moll, Klaus-Peter; Kleinebudde, Peter

doi:10.1016/j.ijpharm.2015.05.060

Cited by 29 publications

(12 citation statements)

References 37 publications

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“…These multimodal distributions can potentially result in segregation during downstream processing and have a negative effect on the drying uniformity. Efforts have been made to obtain monomodal GSD after continuous granulation through optimization of the feeder performance, screw design, binder addition, liquid pump, nozzle design and operation at low filling degree [22,28,30,35,36]. However, for granulation of HPMC bimodal distributions were also reported on high shear granulation which was attributed to the specific vs. F9 in Figure 3).…”

Section: Influence Of Formulation Variables On Granule Qualitymentioning

confidence: 99%

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Vanhoorne

Janssens

Vercruysse

et al. 2016

International Journal of Pharmaceutics

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HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation.The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24 h with release profiles close to zero-order.The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

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Section: Influence Of Formulation Variables On Granule Qualitymentioning

confidence: 99%

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Vanhoorne

Janssens

Vercruysse

et al. 2016

International Journal of Pharmaceutics

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“…In this study, the authors reported the in-line monitoring of the granules processed via a bespoke image analysis technique. The TSG process followed by tabletting in a continuous mode of operation were reported by Meier et al [64]. Kelly et al [65] designed a novel transflectance NIR probe to simultaneously measure the drug and plasticizer content of polymer melts with varying opacity during a continuous HME process.…”

Section: Applications Via Hmementioning

confidence: 99%

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

Maniruzzaman

Nokhodchi

2017

Drug Discovery Today

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A c c e p t e d M a n u s c r i p t Highlights  HME can be exploited in a broad range of applications for advanced drug delivery  Unique advantages to be utilised in a solvent free manufacturing platform  A means to explore the potential of continuous manufacture of pharmaceuticals  Scale-up issue considerations, from an FDA compliance point of view  HME regulatory guidelines for the manufacture of novel drug delivery systems Ali NokhodchiAli Nokhodchi is a professor of pharmaceutics and drug delivery at the University of Sussex. He has supervised over 120 Mpharm, PharmD, and MSc students and 15 PhD postgraduate students at several institutions in various fields of pharmaceutical formulations and drug delivery. He is an editorial board member of over 20 peer-reviewed international journals. Ali has published over 185 research articles in various fields of pharmaceutics, including tableting, particle engineering, inhalation, nanoparticles, dissolution, skin delivery, and controlled-release formulations. In addition, he has published five book chapters on skin, controlled-release formulations, particle engineering, and inhalation products. Ali has also been the editor of a book on pulmonary delivery published by Wiley in 2015. He has been the recipient of several prizes in pharmaceutical sciences and has been listed by Essential Science Indicators in the top 1% scientists in the field of pharmacology and toxicology.Currently, because globalization, the pharmaceutical industry is facing enormous challenges to comply with regulatory matters. Reduced patent life and overall decreased profitability of newly discovered drugs are also forcing the pharmaceutical industry to shorten the drug development time with maximum throughput. Therefore, continuous manufacturing (CM) processes via hot melt extrusion (HME) can be a promising alternative for achieving these goals. HME offers solvent-free green technology with a process that is easy to scale up. Moreover, CM provides better product quality assurance compared with batch processes, with fewer labor costs and shorter time to development. In this review, we primarily focus on various aspects of CM and the emerging application of HME to bridge the current manufacturing gap in pharmaceutical sphere.

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“…For further details of the pump, the reader is referred to previously published studies. 4,14 Liquid feed rate was monitored by a Coriolis mass flow measurement system (Proline Promass 80A; EndressþHauser, Weil am Rhein, Germany). The applied liquid to solid ratios (L/S) are specified in Table 1.…”

Section: Twin Screw Granulationmentioning

confidence: 99%

“…In recent years, numerous research groups and companies have committed their efforts to this topic. [1][2][3][4][5][6][7] Most of the studies examined process analytical tools for TSG or the influence of process parameters on critical quality attributes (CQAs) of granules or subsequently produced tablets. [8][9][10][11][12][13][14] In these studies, the pharmaceutical formulations were often kept constant, resulting in little data on formulation dependencies of the process.…”

Section: Introductionmentioning

confidence: 99%

“…The importance of this must not be neglected, because previous studies observed an oppositional influence of formulation parts on the resulting CQAs. 4,20 Simplified formulations with high drug loads for use in TSG processes were developed in order to decrease the number of used excipients, and to allow a reduction in the number of applied powder feeders within a continuously running environment. The simplified formulations contained approximately 87% of active pharmaceutical ingredient (API), 10% of disintegrants, 3% of binder, and were compressed to tablets after wet granulation and drying.…”

Section: Introductionmentioning

confidence: 99%

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How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant

Meier

Moll

Krumme

et al. 2017

Journal of Pharmaceutical Sciences

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This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule.

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Simplified formulations with high drug loads for continuous twin-screw granulation

Cited by 29 publications

References 37 publications

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant

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