Examining drug hydrophobicity in continuous wet granulation within a twin screw extruder

Li, H.; Thompson, Michael R.; O’Donnell, K. P.

doi:10.1016/j.ijpharm.2015.07.070

Cited by 26 publications

(14 citation statements)

References 30 publications

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“…Similarly, Al-Asady et al [59] investigated different materials (microcrystalline cellulose, hydroxypropyl methylcellulose, Maltodextrin, lactose, sodium carbonate, and calcium carbonate) for nanoindentation hardness produced via a granulation approach. The influence of API hydrophobicity on continuous wet granulation was studied in a foamed twin-screw granulation by Li et al [60].…”

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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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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“…The repeated observations that pressure was not always detectable in Zone 2 when granules were produced diminishes the belief that plastic energy dissipation significantly contributed to binder melting but since the pressure transducer may not detect squeezing forces on powders in the intermeshing region between the two rotating kneading block elements, this mode of heating was not fully discounted either. The dependency on friction energy dissipation (and possibly plastic energy dissipation) means that the mechanism for granule development by assisted dry granulation is different from twin‐screw melt granulation, which are primarily reliant on conductive heating.…”

Section: Mechanism Of Assisted Twin Screw Dry Granulationmentioning

confidence: 99%

Heat assisted twin screw dry granulation

et al. 2017

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A new “assisted” dry granulation method has been devised for the twin‐screw granulator. The method may be beneficial to drug preparation as it limits heat exposure to only one barrel zone, much shorter than melt granulation. Its mechanism was investigated using four placebo formulations, each containing a polymer binder with a glass transition temperature lower than 130°C. Variables of study included screw configuration, screw speed, barrel zone temperature, and moisture content. Granulated samples were characterized for size and porosity while feed powders were examined for their thermal transitions, interparticle friction, cohesion, and sintering rate. Results indicated that granule coalescence relied on melting of polymer binder in the kneading blocks by a combination of heat conducted from barrel and generated from screw speed friction. Successful granulation was possible with minimal addition of water, although varying the moisture content showed the relevance of the polymer's glass transition temperature and sintering progress. © 2017 American Institute of Chemical Engineers AIChE J, 2017

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“…Mainly, excipients like lactose [3], [4], microcrystalline cellulose [5], dicalcium phosphate, or mixtures thereof were used. Some formulations also contained active pharmaceutical ingredients (API), focusing on variation in API particle size [5], API hydrophobicity [6] or drug load [7]. For a tabular overview the reader is referred to the review of M. Tezyk [8].…”

Section: Introductionmentioning

confidence: 99%

A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes

Willecke

Szepes

Wunderlich

et al. 2018

International Journal of Pharmaceutics

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The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous twin screw wet granulation process. The knowledge gained in this study is intended to be used for Quality by Design (QbD)-based formulation design and formulation optimization. Three principal components which represent the overarching properties of 8 selected pharmaceutical fillers were used as factors, whereas factors 4 and 5 represented binder type and binder concentration in a design of experiments (DoE). The majority of process parameters were kept constant to minimize their influence on the granule and drug product quality. 27 DoE batches consisting of binary filler/binder mixtures were processed via continuous twin screw wet granulation followed by tablet compression. Multiple linear regression models were built providing understanding of the impact of filler and binder properties on granule and tablet quality attributes (i.e. 16 DoE responses). The impact of fillers on the granule and tablet responses was more dominant compared to the impact of binder type and concentration. The filler properties had a relevant effect on granule characteristics, such as particle size, friability and specific surface area. Binder type and concentration revealed a relevant influence on granule flowability and friability as well as on the compactability (required compression force during tableting to obtain target hardness). In order to evaluate the DoE models' validity, a verification of the DoE models was performed with new formulations (i.e. a new combination of filler, binder type and binder concentration) which were initially not included in the dataset used to build the DoE models. The combined PCA (principle component analysis)/DoE approach allowed to link the excipient properties with the drug product quality attributes.

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Examining drug hydrophobicity in continuous wet granulation within a twin screw extruder

Cited by 26 publications

References 30 publications

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

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

Heat assisted twin screw dry granulation

A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes

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