Method for preparation of effervescent granules
Inventors
Weiss, Gerd • HÖBART, Hans • Schiemenz, Wolfgang
Assignees
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Publication Number
US-12194139-B2
Publication Date
2025-01-14
Expiration Date
Abstract
The invention provides a method for the preparation of effervescent granules wherein the reactive, effervescent components (one acidic and one alkaline CO2-generating component) are brought to reaction with one another under stirring in a vacuum (100-900 mbar) in an evacuable mixing chamber, with said mixing chamber being evacuated to a first vacuum value p1, and then ‘re-evacuated’ to said first vacuum value p1 again, optionally repeatedly, once the pressure has increased to a second vacuum value p2 due to the progressing CO2 formation of the effervescent reaction. The method is carried out in such a way that during at least the effervescent reaction step(s) the stirring speed in the mixing chamber exhibits a Froude number (Fr) of 0.5 or higher, preferably 0.8 or higher, more preferably 0.9 or higher; such as, in the range of 0.50 to 8.00, or 0.80 to 8.00, or 0.90 to 8.00.
Core Innovation
The invention provides a method for the preparation of effervescent granules in which at least one acidic effervescent component and at least one alkaline CO2-generating effervescent component are brought to reaction with one another under stirring in a vacuum in an evacuable mixing chamber. After loading the reactive components, the mixing chamber is evacuated to a first vacuum value p1 and then evacuated to said first vacuum value p1 again, optionally repeatedly, once the pressure has increased to a second vacuum value p2 as a result of progressing CO2-formation of the effervescent reaction in the mixing chamber. The effervescent reaction is carried out in a vacuum range p1 to p2 of 100 to 900 mbar.
The method stops the effervescent reaction by drying the effervescent granules under vacuum in a "stop"-drying step. During at least the effervescent reaction step(s), the stirring speed in the mixing chamber exhibits a Froude number (Fr) in the range of 0.50 to 8.00. The vacuum-cycling approach provides a reaction environment in which CO2 formation causes a pressure rise from p1 toward p2, followed by re-evacuation back to p1, under controlled vacuum cycling.
The disclosed process is motivated in relation to prior art vacuum systems and describes differences versus prior art approaches that use controlled "pendulum vacuum" but previously involve low stirring. The examples compare embodiments with optimized Froude number ranges to embodiments with lower Froude number and to WO9421239A1. The reported outcomes include improved yields, changes in density and particle distribution, reduced processing time, and improved product properties such as tablet hardness and dissolution, together with storage stability and stability-related performance.
Claims Coverage
The independent claim set is centered on making effervescent granules by vacuum cycling in an evacuable mixing chamber and controlling stirring intensity via a Froude number, while stopping the reaction using vacuum "stop"-drying. The main inventive features are defined in the independent claim and further refined in dependent claims.
Vacuum-cycled evacuable mixing chamber for CO2-formation
An evacuable mixing chamber is used for bringing at least one acidic effervescent component and at least one alkaline CO2-generating effervescent component to reaction with one another under stirring in a vacuum.
Evacuate to first vacuum value p1 and re-evacuate after pressure rises to second vacuum value p2
After loading at least the reactive components, the mixing chamber is evacuated to a first vacuum value p1 and the mixing chamber is evacuated to said first vacuum value p1 again, optionally repeatedly, once the pressure has increased to a second vacuum value p2 as a result of progressing CO2-formation of the effervescent reaction in the mixing chamber.
Effervescent reaction in vacuum range p1 to p2 of 100 to 900 mbar
The effervescent reaction is carried out in a vacuum range p1 to p2 of 100 to 900 mbar.
Stop-drying under vacuum to stop the effervescent reaction
The effervescent reaction is stopped by drying the effervescent granules under vacuum in a "stop"-drying step.
Stirring speed characterized by Froude number Fr between 0.50 and 8.00
During at least the effervescent reaction step(s) a stirring speed in the mixing chamber exhibits a Froude number (Fr) in the range of 0.50 to 8.00.
Froude number and pressure-difference constraints as dependent refinements
The difference between p1 and p2 during the effervescent reaction step is set to 200–500 mbar, 250–450 mbar, or 300–400 mbar.
Higher stirring speed during effervescent reaction than during stop-drying
The stirring speed in the mixing chamber is higher during the effervescent reaction step(s) than during the "stop"-drying step(s).
Top-spray nozzle introduction of the granulating liquid
The granulating liquid is introduced into the evacuable mixing chamber via at least one top-spray nozzle.
Multi-fraction granulating liquid with intermediate stop-drying
The granulating liquid is added in two or more fractions with an intermediate "stop"-drying step between the additions.
Acidic effervescent component as selected organic acids
The acidic effervescent component is an organic acid or mixture of organic acids selected from citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, or mixtures thereof.
Overall, the claims define effervescent granule preparation using vacuum cycling (evacuation to p1, re-evacuation after pressure rises to p2), with the reaction occurring in 100–900 mbar and being terminated by vacuum "stop"-drying. The stirring during the effervescent reaction is controlled via a Froude number range of 0.50–8.00, with dependent claims further refining pressure differences, relative stirring speeds, and granulating-liquid introduction and fractionation, and specifying exemplary acidic effervescent components.
Stated Advantages
Improved yields (e.g., 78% versus 68% reported in examples/ comparisons).
Shorter processing time (e.g., 175 versus 240 min reported in comparisons).
Reduced fine/coarse fractions and improved density/particle distribution.
Improved tablet hardness and dissolution performance.
Improved storage stability and stability-related performance (as discussed in examples).
Documented Applications
Effervescent granule production for forming effervescent tablet-related properties such as tablet hardness and dissolution performance (as discussed in examples).
Comparison of the disclosed method against prior art (WO9421239A1) and against embodiments with different stirring intensity ranges (Froude number) in the context of effervescent granule preparation.
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