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Int J Pharm. 2019 Nov 25;571:118760. doi: 10.1016/j.ijpharm.2019.118760. Epub 2019 Oct 14.

Native starch as in situ binder for continuous twin screw wet granulation.

Author information

1
Ghent University, Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Gent, Belgium. Electronic address: lise.vandevivere@ugent.be.
2
Ghent University, Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Gent, Belgium. Electronic address: christoph.portier@ugent.be.
3
Ghent University, Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Gent, Belgium. Electronic address: valerie.vanhoorne@ugent.be.
4
Roquette Frères, Rue de la Haute Loge, 62136 Lestrem, France. Electronic address: olaf.haeusler@roquette.com.
5
Roquette Frères, Rue de la Haute Loge, 62136 Lestrem, France. Electronic address: denis.simon@roquette.com.
6
Ghent University, Laboratory of Pharmaceutical Process Analytical Technology, Ottergemsesesteenweg 460, 9000 Ghent, Belgium. Electronic address: thomas.debeer@ugent.be.
7
Ghent University, Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Gent, Belgium. Electronic address: chris.vervaet@ugent.be.

Abstract

The use of native starch as in situ binder in a continuous twin screw wet granulation process was studied. Gelatinization of pea starch occurred in the barrel of the granulator using a poorly soluble excipient (anhydrous dicalcium phosphate), but the degree of gelatinization depended on the liquid-to-solid ratio, the granule heating and the screw configuration. Furthermore, the degree of starch gelatinization was correlated with the granule quality: higher binder efficiency was observed in runs where starch was more gelatinized. SEM and PLOM images showed experimental runs which resulted in completely gelatinized starch. Other starch types (maize, potato and wheat starch) could also be gelatinized when processed above a critical barrel temperature for gelatinization. This barrel temperature was different for all starches. In situ starch gelatinization was also investigated in combination with a highly soluble excipient (mannitol). The lower granule friability observed using pure mannitol compared to a mannitol/starch mixture indicated that starch did not contribute to the binding, hence starch did not gelatinize during processing. The study showed that native starch can be considered as a promising in situ binder for continuous twin screw wet granulation of a poorly soluble formulation.

KEYWORDS:

Binder; Continuous manufacturing; Continuous wet granulation; Gelatinization; Granule properties; Native starch; Twin screw granulator

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