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Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation.
Int J Pharm. 2016 Jun 15; 506(1-2):13-24.IJ

Abstract

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, less-soluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different.

Authors+Show Affiliations

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 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

27094358

Citation

Vanhoorne, V, et al. "Improved Tabletability After a Polymorphic Transition of Delta-mannitol During Twin Screw Granulation." International Journal of Pharmaceutics, vol. 506, no. 1-2, 2016, pp. 13-24.
Vanhoorne V, Bekaert B, Peeters E, et al. Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation. Int J Pharm. 2016;506(1-2):13-24.
Vanhoorne, V., Bekaert, B., Peeters, E., De Beer, T., Remon, J. P., & Vervaet, C. (2016). Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation. International Journal of Pharmaceutics, 506(1-2), 13-24. https://doi.org/10.1016/j.ijpharm.2016.04.025
Vanhoorne V, et al. Improved Tabletability After a Polymorphic Transition of Delta-mannitol During Twin Screw Granulation. Int J Pharm. 2016 Jun 15;506(1-2):13-24. PubMed PMID: 27094358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation. AU - Vanhoorne,V, AU - Bekaert,B, AU - Peeters,E, AU - De Beer,T, AU - Remon,J-P, AU - Vervaet,C, Y1 - 2016/04/16/ PY - 2016/03/17/received PY - 2016/04/12/revised PY - 2016/04/13/accepted PY - 2016/4/21/entrez PY - 2016/4/21/pubmed PY - 2017/4/13/medline KW - Continuous production KW - Plastic deformability KW - Polymorphism KW - Tabletability KW - Twin screw granulation KW - δ-mannitol SP - 13 EP - 24 JF - International journal of pharmaceutics JO - Int J Pharm VL - 506 IS - 1-2 N2 - In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, less-soluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/27094358/Improved_tabletability_after_a_polymorphic_transition_of_delta_mannitol_during_twin_screw_granulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(16)30309-X DB - PRIME DP - Unbound Medicine ER -