Continuous API-crystal coating via coacervation in a tubular reactor

Besenhard, Maximilian O.; Thurnberger, A.; Hohl, Roland; Faulhammer, Eva; Rattenberger, Johannes; Khinast, Johannes G.

doi:10.1016/j.ijpharm.2014.08.009

Cited by 10 publications

(8 citation statements)

References 55 publications

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“…In order to avoid premature release of ketoprofen, D-MCs were coated with the gastro-resistant polymer Eudragit ® L100. The in vitro dissolution studies ( Figure 4) confirmed that this polymer successfully protected the drug during transit through the gastric environment and dissolved quickly upon arrival in the small intestine (where the pH is generally above 6) 19, [43][44][45][46] . Spray coating by an ultrasonic nozzle was selected as the technology to deposit the coating onto the cavity of the D-MCs.…”

Section: Accepted Manuscriptmentioning

confidence: 79%

From concept to in vivo testing: Microcontainers for oral drug delivery

Mazzoni

Tentor

Strindberg

et al. 2017

Journal of Controlled Release

101

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This work explores the potential of polymeric micrometer sized devices (microcontainers) as oral drug delivery systems (DDS). Arrays of detachable microcontainers (D-MCs) were fabricated on a sacrificial layer to improve the handling and facilitate the collection of individual D-MCs. A model drug, ketoprofen, was loaded into the microcontainers using supercritical CO impregnation, followed by deposition of an enteric coating to protect the drug from the harsh gastric environment and to provide a fast release in the intestine. In vitro, in vivo and ex vivo studies were performed to assess the viability of the D-MCs as oral DDS. D-MCs improved the relative oral bioavailability by 180% within 4h, and increased the absorption rate by 2.4 times compared to the control. This work represents a significant step forward in the translation of these devices from laboratory to clinic.

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Section: Accepted Manuscriptmentioning

confidence: 79%

From concept to in vivo testing: Microcontainers for oral drug delivery

Mazzoni

Tentor

Strindberg

et al. 2017

Journal of Controlled Release

101

View full text Add to dashboard Cite

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“…12,13,18,22 First studies applying the HCT for API coating and crystal growth were published by Khinast and co-workers. 18,23,24,25,26,27 A sonicated tubular crystallizer was designed by Furuta et al 22 The HCT has not yet been investigated for crystal shape control, although the shape strongly determines API efficacy 6 as well as downstream processing. 2 Therefore, the objective of this work is to apply methods for shape control to the continuous HCT crystallizer to grow crystals with a narrow CSSD.…”

Section: Introductionmentioning

confidence: 99%

Continuous Crystallization in a Helically Coiled Flow Tube: Analysis of Flow Field, Residence Time Behavior, and Crystal Growth

Wiedmeyer

Anker

Bartsch

et al. 2017

Ind. Eng. Chem. Res.

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A continuously operated helically coiled flow tube (HCT) crystallizer is investigated for crystal growth. Inline video-imaging is used for crystal shape analysis and residence time estimation of potash alum. The main finding is that there is a size-dependent particle residence time. Large particles move faster through the HCT than small particles. Consequently, small crystals have more time to grow in the HCT. Physical reasons for this behavior are proposed, for example small-scale flow characteristics. In a direct numerical simulation of the instationary Navier-Stokes equations, velocity fluctuations and a secondary flow are identified. The presented flow field may have a different impact on the particles and cause the size-dependent particle residence time. A particle size dependent residence time may potentially narrow the crystal size and shape distribution in such a process, frequently a desired feature in solids' production.

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“…In another technique to achieve continuous API crystal coating, API was suspended in an aqueous solution containing polymers, fed into a tubular reactor and mixed continuously with a sodium sulfate solution as an antisolvent to induce coacervation. 56 Templated heteronucleation presents an alternative approach for combining API and nonactive components. 57 In a novel continuous heterogeneous crystallization process, the API (acetaminophen) was crystallized directly on the surface of an excipient.…”

Section: ■ Routes To Generate Co-processed Apimentioning

confidence: 99%

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

et al. 2020

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Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining consistent drug product critical quality attributes. However, an appreciable number of APIs have physical properties that cannot be managed via routes such as form selection, adjustments to the crystallization process parameters, or milling. Approaches to control physical properties in innovative ways offer the possibility of providing additional and unique opportunities to control API physical properties for both batch and continuous drug product manufacturing, ultimately resulting in simplified and more robust pharmaceutical manufacturing processes. Specifically, diverse opportunities to significantly enhance API physical properties are created if allowances are made for generating co-processed APIs by introducing nonactive components (e.g., excipients, additives, carriers) during drug substance manufacturing. The addition of a nonactive coformer during drug substance manufacturing is currently an accepted approach for cocrystals, and it would be beneficial if a similar allowance could be made for other nonactive components with the ability to modify the physical properties of the API. In many cases, co-processed APIs could enable continuous direct compression for small molecules, and longer term, this approach could be leveraged to simplify continuous end-to-end drug substance to drug product manufacturing processes for both small and large molecules. As with any novel technology, the regulatory expectations for co-processed APIs are not yet clearly defined, and this creates challenges for commercial implementation of these technologies by the pharmaceutical industry. The intent of this paper is to highlight the opportunities and growing interest in realizing the benefits of co-processed APIs, exemplified by a body of academic research and industrial examples. This work will highlight reasons why co-processed APIs would best be considered as drug substances from a regulatory perspective and emphasize the areas where regulatory strategies need to be established to allow for commercialization of innovative approaches in this area.

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Continuous API-crystal coating via coacervation in a tubular reactor

Cited by 10 publications

References 55 publications

From concept to in vivo testing: Microcontainers for oral drug delivery

From concept to in vivo testing: Microcontainers for oral drug delivery

Continuous Crystallization in a Helically Coiled Flow Tube: Analysis of Flow Field, Residence Time Behavior, and Crystal Growth

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

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