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Cocrystalization and Simultaneous Agglomeration Using Hot Melt Extrusion

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ABSTRACT

Purpose

To explore hot melt extrusion (HME) as a scalable, solvent-free, continuous technology to design cocrystals in agglomerated form.

Methods

Cocrystal agglomerates of ibuprofen and nicotinamide in 1:1 ratio were produced using HME at different barrel temperature profiles, screw speeds, and screw configurations. Product was characterized for crystallinity by XRPD and DSC, while the morphology was determined by SEM. Dissolution rate and tabletting properties were compared with ibuprofen.

Results

Process parameters significantly affected the extent of cocrystallization which improved with temperature, applied shear and residence time. Processing above eutectic point was required for cocrystallization to occur, and it improved with mixing intensity by changing screw configuration. Product was in the form of spherical agglomerates, which showed directly compressible nature with enhanced dissolution rate compared to ibuprofen. This marks an important advantage over the conventional techniques, as it negates the need for further size modification steps.

Conclusions

A single-step, scalable, solvent-free, continuous cocrystallization and agglomeration technology was developed using HME, offering flexibility for tailoring the cocrystal purity. HME being an established technology readily addresses the regulatory demand of quality by design (QbD) and process analytical technology (PAT), offering high potential for pharmaceuticals.

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Abbreviations

DSC:

differential scanning calorimetry

HME:

hot melt extrusion

Ibu-Nic cocrystal:

ibuprofen-nicotinamide 1:1 cocrystal

NIR:

near infra red

PAT:

process analytical technology

PM:

physical mixture of ibuprofen and nicotinamide

Py:

mean yield pressure

QbD:

quality by design

SEM:

scanning electron microscopy

XRPD:

X-ray powder diffractometry

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ACKNOWLEDGEMENTS

Yorkshire Concept, Proof of Concept Funding, Yorkshire Forward, UK. The authors gratefully acknowledge the technical assistance of Andy Baker, Thermo Scientific, UK.

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Authors and Affiliations

  1. Centre for Pharmaceutical Engineering Science and Institute of Pharmaceutical Innovation, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK

    Ravindra S. Dhumal & Anant Paradkar

  2. Centre for Pharmaceutical Engineering Science and IRC in Polymer Engineering, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK

    Adrian L. Kelly

  3. Institute of Pharmaceutical Innovation, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK

    Peter York

  4. IRC in Polymer Engineering, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK

    Phil D. Coates

Authors
  1. Ravindra S. Dhumal
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  2. Adrian L. Kelly
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  3. Peter York
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  4. Phil D. Coates
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  5. Anant Paradkar
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Correspondence to Anant Paradkar.

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Dhumal, R.S., Kelly, A.L., York, P. et al. Cocrystalization and Simultaneous Agglomeration Using Hot Melt Extrusion. Pharm Res 27, 2725–2733 (2010). https://doi.org/10.1007/s11095-010-0273-9

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  • DOI: https://doi.org/10.1007/s11095-010-0273-9

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