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Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation.
Int J Pharm. 2020 Jun 15; 583:119374.IJ

Abstract

In current study, it was investigated if the moisture-mediated polymorphic transition from δ- to β-mannitol during twin screw granulation (TSG) also took place in high drug loaded formulations and if the specific granule morphology associated with the polymorphic transition could enable tableting of granules comprising 75% paracetamol, a poorly compactable drug. Experiments were performed on an integrated continuous manufacturing line, including a twin screw granulator, fluid bed dryer, mill and tablet press. The polymorphic transition of δ- to β-mannitol was observed during twin screw granulation and granules exhibited the needle-shaped morphology, typical of this transition. TSG at low liquid-to-solid (L/S) ratios and use of polyvinylpyrrolidone or hydroxypropylmethylcellulose as binders inhibited the polymorphic transition, whereas screw speed, drying time, drying temperature and airflow did not affect the solid state of mannitol in the granules. Without binder and despite the high paracetamol drug load in the formulation, limited breakage and attrition was observed during drying and milling. In contrast to granules manufactured from a formulation containing paracetamol/β-mannitol which could not be tableted due to extensive capping, granules prepared from a paracetamol/δ-mannitol formulation showed good tabletability. In conclusion, δ-mannitol is a promising TSG excipient, especially for high drug-loaded formulations with poor tabletability.

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 Technology, Ghent University, Belgium. Electronic address: Chris.Vervaet@UGent.be.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

32339631

Citation

Vanhoorne, V, et al. "Delta-mannitol to Enable Continuous Twin-screw Granulation of a Highly Dosed, Poorly Compactable Formulation." International Journal of Pharmaceutics, vol. 583, 2020, p. 119374.
Vanhoorne V, Almey R, De Beer T, et al. Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation. Int J Pharm. 2020;583:119374.
Vanhoorne, V., Almey, R., De Beer, T., & Vervaet, C. (2020). Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation. International Journal of Pharmaceutics, 583, 119374. https://doi.org/10.1016/j.ijpharm.2020.119374
Vanhoorne V, et al. Delta-mannitol to Enable Continuous Twin-screw Granulation of a Highly Dosed, Poorly Compactable Formulation. Int J Pharm. 2020 Jun 15;583:119374. PubMed PMID: 32339631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation. AU - Vanhoorne,V, AU - Almey,R, AU - De Beer,T, AU - Vervaet,C, Y1 - 2020/04/24/ PY - 2020/03/03/received PY - 2020/04/22/revised PY - 2020/04/23/accepted PY - 2020/4/28/pubmed PY - 2021/2/27/medline PY - 2020/4/28/entrez KW - Continuous production KW - Granular morphology KW - Polymorphism KW - Tabletability KW - Twin screw granulation KW - δ-mannitol SP - 119374 EP - 119374 JF - International journal of pharmaceutics JO - Int J Pharm VL - 583 N2 - In current study, it was investigated if the moisture-mediated polymorphic transition from δ- to β-mannitol during twin screw granulation (TSG) also took place in high drug loaded formulations and if the specific granule morphology associated with the polymorphic transition could enable tableting of granules comprising 75% paracetamol, a poorly compactable drug. Experiments were performed on an integrated continuous manufacturing line, including a twin screw granulator, fluid bed dryer, mill and tablet press. The polymorphic transition of δ- to β-mannitol was observed during twin screw granulation and granules exhibited the needle-shaped morphology, typical of this transition. TSG at low liquid-to-solid (L/S) ratios and use of polyvinylpyrrolidone or hydroxypropylmethylcellulose as binders inhibited the polymorphic transition, whereas screw speed, drying time, drying temperature and airflow did not affect the solid state of mannitol in the granules. Without binder and despite the high paracetamol drug load in the formulation, limited breakage and attrition was observed during drying and milling. In contrast to granules manufactured from a formulation containing paracetamol/β-mannitol which could not be tableted due to extensive capping, granules prepared from a paracetamol/δ-mannitol formulation showed good tabletability. In conclusion, δ-mannitol is a promising TSG excipient, especially for high drug-loaded formulations with poor tabletability. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/32339631/Delta_mannitol_to_enable_continuous_twin_screw_granulation_of_a_highly_dosed_poorly_compactable_formulation_ DB - PRIME DP - Unbound Medicine ER -