Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction

E.O. Ojo, A. Rayat, C.J. Price, C.J. Brown, M. Hoare, A. Johnston, A.J. Florence

Research output: Contribution to conferencePoster

1 Citation (Scopus)

Abstract

The use of scale down devices for early-stage process development enables early availability of experimental data, indicative of large-scale processes. In this work, an automated ultra scale-down (USD) filtration and a shear device which when used together allow the study of the recovery of active pharmaceutical ingredients (API) of different crystal particle size distributions at 10s of milligram-scale. For an early understanding of the process interactions based on a simple DoE design, a pressure difference of 70 kPa was observed to be significant for the filtration process when the 5 m filter pore size is used. At all other conditions investigated, the outcomes of the USD filtration were compared with established laboratory-scale filters operating at 10-fold scale based on total working mass. Good comparability was obtained for samples with narrow PSD, while samples with larger PSD had reduced predictive capability. API of narrower PSD was achieved by using a USD shear device and applied mechanical force. For the shear stressed crystals using USD shear device, crystals were found to be robust to shear stress with a small amount of fines produced, and the impact of fines on filtration was not remarkable. Mechanically size reduced crystals produced a substantial amount of fines, which resulted in a considerable reduction of the filtrate flux and approximately ten-fold rise in specific cake resistance when compared with shear stressed crystals. In general, the PSD of the crystals were found to be critical to determining the filtration conditions such as pressure difference and filter pore size. As concluded in this study, PSD is directly related to filter pore size and inversely related to the pressure difference, as would be expected. The implementation of the automated USD filtration platform enables rapid-process understanding and reduces cost and time due to a reduced amount of materials. The data obtained shows similar process trends and are primarily indicative of process performance at a larger scale.

Conference

Conference50th Annual Conference of the British Association of Crystal Growth
CountryUnited Kingdom
CityLondon
Period9/07/1911/07/19

Fingerprint

Drug products
Crystals
Pharmaceutical Preparations
Pore size
Particle size analysis
Shear stress
Availability
Fluxes
Recovery
Costs

Keywords

  • filtration
  • scale-down
  • pharmaceutical
  • crystals

Cite this

Ojo, E. O., Rayat, A., Price, C. J., Brown, C. J., Hoare, M., Johnston, A., & Florence, A. J. (2019). Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction. 88. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom. https://doi.org/10.6084/m9.figshare.9770135.v1
Ojo, E.O. ; Rayat, A. ; Price, C.J. ; Brown, C.J. ; Hoare, M. ; Johnston, A. ; Florence, A.J. / Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.1 p.
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Ojo, EO, Rayat, A, Price, CJ, Brown, CJ, Hoare, M, Johnston, A & Florence, AJ 2019, 'Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction' 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom, 9/07/19 - 11/07/19, pp. 88. https://doi.org/10.6084/m9.figshare.9770135.v1

Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction. / Ojo, E.O.; Rayat, A.; Price, C.J.; Brown, C.J.; Hoare, M.; Johnston, A.; Florence, A.J.

2019. 88 Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.

Research output: Contribution to conferencePoster

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T1 - Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction

AU - Ojo, E.O.

AU - Rayat, A.

AU - Price, C.J.

AU - Brown, C.J.

AU - Hoare, M.

AU - Johnston, A.

AU - Florence, A.J.

PY - 2019/7/11

Y1 - 2019/7/11

N2 - The use of scale down devices for early-stage process development enables early availability of experimental data, indicative of large-scale processes. In this work, an automated ultra scale-down (USD) filtration and a shear device which when used together allow the study of the recovery of active pharmaceutical ingredients (API) of different crystal particle size distributions at 10s of milligram-scale. For an early understanding of the process interactions based on a simple DoE design, a pressure difference of 70 kPa was observed to be significant for the filtration process when the 5 m filter pore size is used. At all other conditions investigated, the outcomes of the USD filtration were compared with established laboratory-scale filters operating at 10-fold scale based on total working mass. Good comparability was obtained for samples with narrow PSD, while samples with larger PSD had reduced predictive capability. API of narrower PSD was achieved by using a USD shear device and applied mechanical force. For the shear stressed crystals using USD shear device, crystals were found to be robust to shear stress with a small amount of fines produced, and the impact of fines on filtration was not remarkable. Mechanically size reduced crystals produced a substantial amount of fines, which resulted in a considerable reduction of the filtrate flux and approximately ten-fold rise in specific cake resistance when compared with shear stressed crystals. In general, the PSD of the crystals were found to be critical to determining the filtration conditions such as pressure difference and filter pore size. As concluded in this study, PSD is directly related to filter pore size and inversely related to the pressure difference, as would be expected. The implementation of the automated USD filtration platform enables rapid-process understanding and reduces cost and time due to a reduced amount of materials. The data obtained shows similar process trends and are primarily indicative of process performance at a larger scale.

AB - The use of scale down devices for early-stage process development enables early availability of experimental data, indicative of large-scale processes. In this work, an automated ultra scale-down (USD) filtration and a shear device which when used together allow the study of the recovery of active pharmaceutical ingredients (API) of different crystal particle size distributions at 10s of milligram-scale. For an early understanding of the process interactions based on a simple DoE design, a pressure difference of 70 kPa was observed to be significant for the filtration process when the 5 m filter pore size is used. At all other conditions investigated, the outcomes of the USD filtration were compared with established laboratory-scale filters operating at 10-fold scale based on total working mass. Good comparability was obtained for samples with narrow PSD, while samples with larger PSD had reduced predictive capability. API of narrower PSD was achieved by using a USD shear device and applied mechanical force. For the shear stressed crystals using USD shear device, crystals were found to be robust to shear stress with a small amount of fines produced, and the impact of fines on filtration was not remarkable. Mechanically size reduced crystals produced a substantial amount of fines, which resulted in a considerable reduction of the filtrate flux and approximately ten-fold rise in specific cake resistance when compared with shear stressed crystals. In general, the PSD of the crystals were found to be critical to determining the filtration conditions such as pressure difference and filter pore size. As concluded in this study, PSD is directly related to filter pore size and inversely related to the pressure difference, as would be expected. The implementation of the automated USD filtration platform enables rapid-process understanding and reduces cost and time due to a reduced amount of materials. The data obtained shows similar process trends and are primarily indicative of process performance at a larger scale.

KW - filtration

KW - scale-down

KW - pharmaceutical

KW - crystals

U2 - 10.6084/m9.figshare.9770135.v1

DO - 10.6084/m9.figshare.9770135.v1

M3 - Poster

SP - 88

ER -

Ojo EO, Rayat A, Price CJ, Brown CJ, Hoare M, Johnston A et al. Unconventional ultra scale-down techniques for active pharmaceutical ingredient filtration and size reduction. 2019. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom. https://doi.org/10.6084/m9.figshare.9770135.v1