High-shear granulation as a manufacturing method for cocrystal granules

Research output: Contribution to journalJournal article

Standard

High-shear granulation as a manufacturing method for cocrystal granules. / Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka; Rades, Thomas; Leopold, Claudia S.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 85, No. 3, Part B, 11.2013, p. 1019-30.

Research output: Contribution to journalJournal article

Harvard

Rehder, S, Christensen, NPA, Rantanen, J, Rades, T & Leopold, CS 2013, 'High-shear granulation as a manufacturing method for cocrystal granules', European Journal of Pharmaceutics and Biopharmaceutics, vol. 85, no. 3, Part B, pp. 1019-30. https://doi.org/10.1016/j.ejpb.2013.04.022

APA

Rehder, S., Christensen, N. P. A., Rantanen, J., Rades, T., & Leopold, C. S. (2013). High-shear granulation as a manufacturing method for cocrystal granules. European Journal of Pharmaceutics and Biopharmaceutics, 85(3, Part B), 1019-30. https://doi.org/10.1016/j.ejpb.2013.04.022

Vancouver

Rehder S, Christensen NPA, Rantanen J, Rades T, Leopold CS. High-shear granulation as a manufacturing method for cocrystal granules. European Journal of Pharmaceutics and Biopharmaceutics. 2013 Nov;85(3, Part B):1019-30. https://doi.org/10.1016/j.ejpb.2013.04.022

Author

Rehder, Sönke ; Christensen, Niels Peter Aae ; Rantanen, Jukka ; Rades, Thomas ; Leopold, Claudia S. / High-shear granulation as a manufacturing method for cocrystal granules. In: European Journal of Pharmaceutics and Biopharmaceutics. 2013 ; Vol. 85, No. 3, Part B. pp. 1019-30.

Bibtex

@article{f660d30d2dcd422f9cb8a13273403e69,
title = "High-shear granulation as a manufacturing method for cocrystal granules",
abstract = "Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation as a manufacturing method for cocrystal granules on a batch scale. Furthermore, the cocrystal granules were characterized regarding their mechanical properties as well as their dissolution behavior. High-shear wet granulation was found to be a feasible manufacturing method for cocrystal granules. Cocrystal formation depended on the exposure time of the solids to the granulation liquid (water), the amount of liquid, the impeller speed of the granulator, and on the excipients (hydroxyl propylcellulose, microcrystalline cellulose, calcium hydrogenphosphate) used in the formulation. Storage stability was strongly influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.",
author = "S{\"o}nke Rehder and Christensen, {Niels Peter Aae} and Jukka Rantanen and Thomas Rades and Leopold, {Claudia S}",
note = "Copyright {\circledC} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = "11",
doi = "10.1016/j.ejpb.2013.04.022",
language = "English",
volume = "85",
pages = "1019--30",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "3, Part B",

}

RIS

TY - JOUR

T1 - High-shear granulation as a manufacturing method for cocrystal granules

AU - Rehder, Sönke

AU - Christensen, Niels Peter Aae

AU - Rantanen, Jukka

AU - Rades, Thomas

AU - Leopold, Claudia S

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/11

Y1 - 2013/11

N2 - Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation as a manufacturing method for cocrystal granules on a batch scale. Furthermore, the cocrystal granules were characterized regarding their mechanical properties as well as their dissolution behavior. High-shear wet granulation was found to be a feasible manufacturing method for cocrystal granules. Cocrystal formation depended on the exposure time of the solids to the granulation liquid (water), the amount of liquid, the impeller speed of the granulator, and on the excipients (hydroxyl propylcellulose, microcrystalline cellulose, calcium hydrogenphosphate) used in the formulation. Storage stability was strongly influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.

AB - Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation as a manufacturing method for cocrystal granules on a batch scale. Furthermore, the cocrystal granules were characterized regarding their mechanical properties as well as their dissolution behavior. High-shear wet granulation was found to be a feasible manufacturing method for cocrystal granules. Cocrystal formation depended on the exposure time of the solids to the granulation liquid (water), the amount of liquid, the impeller speed of the granulator, and on the excipients (hydroxyl propylcellulose, microcrystalline cellulose, calcium hydrogenphosphate) used in the formulation. Storage stability was strongly influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.

U2 - 10.1016/j.ejpb.2013.04.022

DO - 10.1016/j.ejpb.2013.04.022

M3 - Journal article

VL - 85

SP - 1019

EP - 1030

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 3, Part B

ER -

ID: 109627523