Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

Içten, Elçin; Giridhar, Arun; Nagy, Zoltán K.; Reklaitis, Gintaras V.

doi:10.1208/s12249-015-0348-3

Cited by 12 publications

(7 citation statements)

References 25 publications

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“…Dropwise additive manufacturing is another innovative method for the production of final drug products . The principle of the process is the predictable and controllable deposition of a droplet containing an API onto an edible substrate, such as a polymeric film or a placebo tablet.…”

Section: Recent Progress In Continuous Pharmaceutical Technologiesmentioning

confidence: 99%

Integrated Continuous Pharmaceutical Technologies—A Review

Domokos

Nagy

Szilágyi

et al. 2021

Org. Process Res. Dev.

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Innovation in the pharmaceutical industry has been limited for a long time to the research and development of new active compounds; meanwhile, the structure of the production, dominated by batchwise technologies, has not changed to date. As has already been demonstrated in several other industrial sectors, continuous manufacturing (CM) has many advantages over batch processes. Faster, cheaper, and more flexible production can be developed with a significantly higher level of quality assurance. In the recent years the main regulatory agencies recognized the need for a change in drug production and started to promote continuous technologies and encourage pharmaceutical companies to develop and adapt such processes. As a result, by today extensive research was conducted in the various fields of pharmaceutical technologies from drug substance to drug product manufacturing. Many publications deal with synthetic steps carried out in flow reactors and crystallizations implemented in a continuous manner, and on the formulation side continuous filtration, drying, granulation, and blending have all been studied to a lesser or greater extent. Moreover, besides the modification of these traditional processes to continuous operation, novel, intrinsically continuous technologies are being studied as well. In order to entirely exploit the advantages of CM, the mainly separately developed processes need to be integrated to form end-to-end systems from the raw materials to the final dosage forms. However, even the integration of two technological steps is a challenging task. The development of end-to-end systems requires deep process understanding and a holistic approach toward process development and optimization. The aim of this work is to give insight into the state-of-the-art and new directions in integrated continuous pharmaceutical technologies by critically reviewing the recent literature of the broad field.

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Section: Recent Progress In Continuous Pharmaceutical Technologiesmentioning

confidence: 99%

Integrated Continuous Pharmaceutical Technologies—A Review

Domokos

Nagy

Szilágyi

et al. 2021

Org. Process Res. Dev.

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“…The details of the automation program are detailed in our previous publication (Hirshfield et al, 2015). The program enables executing process units in a synchronized fashion while monitoring critical quality attributes, such as dosage amount and drug morphology, online, and controlling critical process parameters, such as drop size, product and process temperatures (Içten et al, 2016a). The automation program is integrated with a Knowledge Management System, which allows the user to save the data provenance related with each drop dose produced via DAMPP (Içten et al, 2016b).…”

Section: Dropwise Additive Manufacturing Process For Lipid-based Formmentioning

confidence: 99%

“…The current level of innovation in dosage form design and drug product manufacturing cannot meet the needs of personalized therapies (Rantanen and Khinast, 2015). While innovation is the key to success within the pharmaceutical industry, it has been largely sought through new drug discovery and development, while the development of new manufacturing methods has received inadequate attention (Içten et al, 2016a). Traditionally the pharmaceutical industry has manufactured its products in large scale batch processes with limited use of on-line process monitoring and active process control technologies.…”

Section: Introductionmentioning

confidence: 99%

Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems

Içten

Purohit

Wallace

et al. 2017

International Journal of Pharmaceutics

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The improvements in healthcare systems and the advent of the precision medicine initiative have created the need to develop more innovative manufacturing methods for the delivery and production of individualized dosing and personalized treatments. In accordance with the changes observed in healthcare systems towards more innovative therapies, this paper presents dropwise additive manufacturing of pharmaceutical products (DAMPP) for small scale, distributed manufacturing of individualized dosing as an alternative to conventional manufacturing methods A dropwise additive manufacturing process for amorphous and self-emulsifying drug delivery systems is reported, which utilizes drop-on-demand printing technology for automated and controlled deposition of melt-based formulations onto inert tablets. The advantages of drop on demand technology include reproducible production of droplets with adjustable sizing and high placement accuracy, which enable production of individualized dosing even for low dose and high potency drugs. Flexible use of different formulations, such as lipid-based formulations, allows enhancement of the solubility of poorly water soluble and highly lipophilic drugs with DAMPP. Here, DAMPP is used to produce solid oral dosage forms from melts of an active pharmaceutical ingredient and a surfactant. The dosage forms are analyzed to show the amorphous nature, self-emulsifying drug delivery system characteristics and dissolution behavior of these formulations.

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“…Alternatively, the melt ink-jet printing allows a good control of the drug solid state and film morphology (Içten et al, 2015;Içten et al, 2016) and the flexographic printing was also tested to impregnate placebo ODF with a precise dose of a drug (Janßen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Personalized orodispersible films by hot melt ram extrusion 3D printing

Musazzi

Selmin

Ortenzi

et al. 2018

International Journal of Pharmaceutics

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This work demonstrates the feasibility of the extemporaneous preparation of maltodextrins orodispersible films (ODF) by hot-melt ram-extrusion 3D printing. This method consists of three simple technological operations which can be also implemented in a pharmacy setting. First, maltodextrins, drug, and other excipients are mixed in a mortar and wetted with the plasticizer (i.e. glycerine). Then, the mixture is fed in the chamber of the ram-extruder and heated. ODF are individually printed on the packaging material foil and sealed without further manipulations. The critical formulation attributes and process variables were investigated to define the processability space. In particular, the optimal conditions to print a mixture of maltodextrins/glycerine in a 80/20 w/w ratio resulted: heating temperature: 85 °C; needle gauge: 18 G; needle-packaging material foil distance: 0.6 mm; maximum print rate: 50 mm/s; filling angle: 120°. The maximum drug loading was about 40%, when paracetamol was used as model drug. The compounded ODF complied with USP and Ph. Eur. specifications for disintegration time (<1 min). The dissolution pattern of paracetamol overlapped with that obtained from ODF with a similar composition prepared by the consolidated solvent casting technique, demonstrating the suitability of the proposed technology.

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Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

Cited by 12 publications

References 25 publications

Integrated Continuous Pharmaceutical Technologies—A Review

Integrated Continuous Pharmaceutical Technologies—A Review

Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems

Personalized orodispersible films by hot melt ram extrusion 3D printing

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