Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion

Wahl, Patrick; Treffer, Daniel Franz; Mohr, Stefan; Roblegg, Eva; Koscher, Gerold; Khinast, Johannes G.

doi:10.1016/j.ijpharm.2013.07.044

Cited by 58 publications

(36 citation statements)

References 18 publications

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“…The NIR probe measured the API content of the melt and provided a better understanding of the factors affecting content uniformity. Three different parameters including the API concentrations, screw speeds, and screw designs were monitored in this experiment (125). The highlighted studies have clearly demonstrated the feasibility and advantages of using PAT strategies including the in-line NIR measurements and Raman spectroscopy in pharmaceutical HME processes.…”

Section: Process Optimization Using Qbd Approachesmentioning

confidence: 95%

“…Several research articles have been published about the application of PAT in HME processes. NIR and Raman spectroscopy are the most common techniques used as PAT tools in the pharmaceutical industry (125)(126)(127)(128)(129), and NIR has been applied in monitoring the API content of extruded films (130)(131)(132). Saerens et al (133) studied the suitability of using Raman spectroscopy as a PAT tool for the in-line polymer-drug quantification and solid-state characterization of a pharmaceutical HME process.…”

Section: Process Optimization Using Qbd Approachesmentioning

confidence: 99%

“…Wahl et al (125) studied the PAT strategy in the production of paracetamol embedded in a calcium stearate matrix via HME. In-line NIR spectroscopy was used as a PAT tool, to monitor the extrusion process, and a probe was located in the section between the extrusion screws and the die using a novel design for the die channel.…”

Section: Process Optimization Using Qbd Approachesmentioning

confidence: 99%

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Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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Abstract. Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

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Section: Process Optimization Using Qbd Approachesmentioning

confidence: 95%

Section: Process Optimization Using Qbd Approachesmentioning

confidence: 99%

Section: Process Optimization Using Qbd Approachesmentioning

confidence: 99%

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Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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“…Similarly, Wahl et al [45] implemented CM via HME processing of vegetable calcium stearate (CaSt) and paracetamol monitored by PAT tools. In this study, the authors used in-line NIR spectroscopy to monitor and control the process by using a novel design of the die.…”

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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“…Near-infrared (NIR) spectroscopy is to date considered one of the most common techniques suitable for varied PAT applications, which have resulted in several studies in the pharmaceutical and nutritional fields. It has been reported that the NIR spectroscopy can be used to facilitate both quantitative and qualitative analysis such as drug crystallinity and polymer-drug or polymer-polymer interactions and the drug dissolution rates during an HME process (18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Novel Controlled Release Polymer-Lipid Formulations Processed by Hot Melt Extrusion

et al. 2015

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Abstract. The aim of the study was to investigate the effect of novel polymer/lipid formulations on the dissolution rates of the water insoluble indomethacin (INM), co-processed by hot melt extrusion (HME). Formulations consisted of the hydrophilic hydroxypropyl methyl cellulose polymer (HPMCAS) and stearoyl macrogol-32 glycerides-Gelucire 50/13 (GLC) were processed with a twin screw extruder to produce solid dispersions. The extrudates characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and hot stage microscopy (HSM) indicated the presence of amorphous INM within the polymer/lipid matrices. In-line monitoring via near-infrared (NIR) spectroscopy revealed significant peak shifts indicating possible interactions and H-bonding formation between the drug and the polymer/lipid carriers. Furthermore, in vitro dissolution studies showed a synergistic effect of the polymer/lipid carrier with 2-h lag time in acidic media followed by enhanced INM dissolution rates at pH>5.5.

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Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion

Cited by 58 publications

References 18 publications

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

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

Novel Controlled Release Polymer-Lipid Formulations Processed by Hot Melt Extrusion

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