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Ring-Extruders for the shear-stress-reduced preparation of solid dispersion containing biological active ingredient in comparison to twin-screw extruders yielding in lower impurities of the pharmaceutical compound

IP.com Disclosure Number: IPCOM000239130D
Publication Date: 2014-Oct-14

Publishing Venue

The IP.com Prior Art Database

Abstract

Solid dispersions are a promising formulation approach to overcome today’s major challenge in pharmaceutical formulation development: poorly soluble and/or poorly permeable active pharmaceutical ingredients (API – also commonly called biological active substance). Solid dispersions can be obtained by different processes, but hot-melt extrusion turned out to show beneficial contributions to a formulation. One advantage is the no-use of solvents which avoids the risk of residual solvents in a formulation which could induce stability issues during shelf life of the formulation. Beside single-screw extruders, for preparation of pharmaceutical formulations or for food processing twin-screw extruders are used. Preferably co-rotating twin-screw extruders are used. Shear stress and temperature are two parameters in the extrusion process which are sometimes seen as negative since too high shear stress and/or too high temperature can lead to a non-acceptable level of degradation products, also called impurities. Hence the authors looked for a way to produce a solid dispersion which will apply much less shear stress and stress in general to the processed material (for pharmaceutical formulations such as a solid dispersion) to yield at least same good mixing intensity as on a twin-screw extruder but with reduced impurities. The authors will show that the use of a so called RingExtruder is beneficial in this approach since it allows intensive mixing under mild shear stress conditions which is expected to yield a lower impurity generation in the extruded product compared to material being processed on a state-of-the-art co-rotating twin screw extruder/compounder. The here discussed RingExtruder from company Extricom uses 12 co-rotating screws arranged in a circle. As material Soluplus was used, a pharmaceutical grade polymer developed especially for the purpose of hot-melt extrusion. The authors discuss the different process conditions between the RingExtruder and a conventional twin screw extruder on process parameters such as residence time distribution, mean residence time, process temperature, specific mechanical energy consumption and the Bodenstein-number (Bodensteinzahl), which is a measure of axial mixing in the extruder. The authors show that a RingExtruder can be used to obtain a process for manufacturing a solid dispersion under much more mild conditions than in a twin screw extruder. This has relevance for active pharmaceutical ingredients (biological active substances) which might be sensitive to shear and/or temperature stress.

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RingExtruders for the shear-stress-reduced preparation of solid dispersion containing biological active ingredient in comparison to twin-screw extruders yielding in lower impurities of the pharmaceutical compound

1 Abstract

Solid dispersions are a promising formulation approach to overcome today's major challenge in pharmaceutical formulation development: poorly soluble and/or poorly permeable active pharmaceutical ingredients (API - also commonly called biological active substance). Solid dispersions can be obtained by different processes, but hot-melt extrusion turned out to show beneficial contributions to a formulation. One advantage is the no-use of solvents which avoids the risk of residual solvents in a formulation which could induce stability issues during shelf life of the formulation. Beside single-screw extruders, for preparation of pharmaceutical formulations or for food processing twin-screw extruders are used. Preferably co-rotating twin-screw extruders are used. Shear stress and temperature are two parameters in the extrusion process which are sometimes seen as negative since too high shear stress and/or too high temperature can lead to a non-acceptable level of degradation products, also called impurities. Hence the authors looked for a way to produce a solid dispersion which will apply much less shear stress and stress in general to the processed material (for pharmaceutical formulations such as a solid dispersion) to yield at least same good mixing intensity as on a twin-screw extruder but with reduced impurities. The authors will show that the use of a so called RingExtruder is beneficial in this approach since it allows intensive mixing under mild shear stress conditions which is expected to yield a lower impurity generation in the extruded product compared to material being processed on a state-of-the-art co-rotating twin screw extruder/compounder. The here discussed RingExtruder from company Extricom uses 12 co- rotating screws arranged in a circle. As material Soluplus was used, a pharmaceutical grade polymer developed especially for the purpose of hot-melt extrusion. The authors discuss the different process conditions between the RingExtruder and a conventional twin screw extruder on process parameters such as residence time distribution, mean residence time, process temperature, specific mechanical energy consumption and the Bodenstein-number (Bodensteinzahl), which is a measure of axial mixing in the extruder. The authors show that a RingExtruder can be used to obtain a process for manufacturing a solid dispersion under much more mild conditions than in a twin screw extruder. This has relevance for active pharmaceutical ingredients (biological active substances) which might be sensitive to shear and/or temperature stress.

2 Introduction

The pharmaceutical industry is facing the challenge of having more and more poorly soluble drug molecules that have to be developed into dosage forms so that high and r...