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Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters.
Int J Pharm. 2016 May 30; 505(1-2):61-8.IJ

Abstract

The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters.

Authors+Show Affiliations

Laboratory of Pharmaceutical Technology, Ghent University, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.Laboratory of Nanotechnology, Centro Universitário Franciscano, Brazil.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Belgium. Electronic address: chris.vervaet@ugent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27041123

Citation

Vanhoorne, V, et al. "Development of a Controlled Release Formulation By Continuous Twin Screw Granulation: Influence of Process and Formulation Parameters." International Journal of Pharmaceutics, vol. 505, no. 1-2, 2016, pp. 61-8.
Vanhoorne V, Vanbillemont B, Vercruysse J, et al. Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters. Int J Pharm. 2016;505(1-2):61-8.
Vanhoorne, V., Vanbillemont, B., Vercruysse, J., De Leersnyder, F., Gomes, P., Beer, T. D., Remon, J. P., & Vervaet, C. (2016). Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters. International Journal of Pharmaceutics, 505(1-2), 61-8. https://doi.org/10.1016/j.ijpharm.2016.03.058
Vanhoorne V, et al. Development of a Controlled Release Formulation By Continuous Twin Screw Granulation: Influence of Process and Formulation Parameters. Int J Pharm. 2016 May 30;505(1-2):61-8. PubMed PMID: 27041123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters. AU - Vanhoorne,V, AU - Vanbillemont,B, AU - Vercruysse,J, AU - De Leersnyder,F, AU - Gomes,P, AU - Beer,T De, AU - Remon,J P, AU - Vervaet,C, Y1 - 2016/03/31/ PY - 2016/02/04/received PY - 2016/03/18/revised PY - 2016/03/29/accepted PY - 2016/4/5/entrez PY - 2016/4/5/pubmed PY - 2017/4/11/medline KW - Continuous production KW - Controlled release KW - Hydroxypropylmethylcellulose KW - Process variables KW - Twin screw granulation KW - Wet granulation SP - 61 EP - 8 JF - International journal of pharmaceutics JO - Int J Pharm VL - 505 IS - 1-2 N2 - The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/27041123/Development_of_a_controlled_release_formulation_by_continuous_twin_screw_granulation:_Influence_of_process_and_formulation_parameters_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(16)30267-8 DB - PRIME DP - Unbound Medicine ER -