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Process and apparatus for cooling and atomizing liquid or pasty-like substances

a technology of atomizing liquid and apparatus, which is applied in the direction of domestic cooling apparatus, ice production, lighting and heating apparatus, etc., can solve the problems of unsuitable process, unsuitable cooling process, and often required relative rapid cooling of substances,

Inactive Publication Date: 2009-08-27
MERCK SERONO SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The object of the invention is to provide a process and an apparatus by which the disadvantages of the prior art are overcome and by which a relatively rapid cooling and atomization of liquid or pasty substances is possible, in particular even relatively small amounts of liquid or pasty substances being able to be cooled and atomized economically.
[0010]During the expansion, small particles of liquid or pasty substances / mixture of substances, spherically-shaped are formed. This leads to a good reproducibility of the process and to a fine particulate with an average diameter comprises between 2 and 100 μm, preferably in ranges of from 5 to 15 μm or from 40 to 80 μm, depending on the nozzle used. Moreover, the particles are always spherically shaped and have a narrow particle size distribution.
[0015]This procedure has the advantage that at a preferred pressure range and temperature range the carbon dioxide can be taken off directly from the supply system, for example low-pressure and medium-pressure tanks or carbon dioxide cylinders, without further gas treatment.
[0024]The apparatus is constructed in such a manner that the mixture of liquid or pasty substance / mixture of substances and gaseous carbon dioxide is not expanded until on exit from the expansion apparatus. A very direct contact takes place out between liquid or pasty substance / mixture of substances and liquid carbon dioxide achieving cooling and atomization of liquid or pasty substance / mixture of substances in the spray tower. The apparatus ensures rapid cooling and atomization of the liquid or pasty substance / mixture of substances. By use of the inventive expansion apparatus, small, easily flowable particles of the liquid or pasty substance / mixture of substances are produced.
[0029]The nozzles for the liquid carbon dioxide and for the mixture of liquid or pasty substance / mixture of substances and gaseous carbon dioxide, advantageously, have a shielding device, preferably a jacket tube. The use of a nozzle having a jacket tube has the advantage that only a small amount of air is taken in or sucked into the stream. The carbon dioxide in this case is at least partially converted into carbon dioxide snow. Typically, approximately 30% by weight of carbon dioxide snow and approximately 70% by weight of gaseous carbon dioxide are formed during the expansion of the liquid carbon dioxide at the nozzle.

Problems solved by technology

A relatively rapid cooling of the substances, which is very frequently required, cannot be achieved by this means.
These cooling processes are also frequently unsuitable for carrying out crystallization or freezing, since insulating deposits form on the cooling surfaces which can impair the cooling process.
For a relatively rapid cooling of liquid or pasty substances this process also is unsuitable, since the cooling in the interior of the substances is determined by the heat transport through the substance itself, and the contact surfaces for a rapid cooling, for example for crystallization, are still too small.
It is virtually impossible with these processes to produce readily meterable flowable substances.
There is the disadvantage here that the product can be cooled as early as in the nozzle by the low-temperature nitrogen and can block this nozzle.
The use of this process for producing microparticles suitable for pharmaceutical purposes, like for example those described in WO 02 / 051386 has the disadvantage of the non-reproducibility of the particle sizes and the large dimensions of the same.

Method used

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  • Process and apparatus for cooling and atomizing liquid or pasty-like substances
  • Process and apparatus for cooling and atomizing liquid or pasty-like substances
  • Process and apparatus for cooling and atomizing liquid or pasty-like substances

Examples

Experimental program
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Effect test

example 1

Preparation of Microparticles According to the Process of the Invention

[0057]1.1 Melting of the Materials and Drug Incorporation into the Matrix:

[0058]The substances to be processed (lipid and / or polymer mixture) are melted in a thermostated bath, at a proper temperature, depending on the substances used. A drug can be added to the molten matrix, under constant stirring. The molten mass is then poured into the feeding vessel of the atomizer, thermostated at a suitable temperature (so to keep the mass in the liquid form). Alternatively, this first melting step can be also performed directly in the feeding vessel of the atomizer, since such vessel is equipped with a stirring tool.

Alternatively a certain amount of solvent can be added to the mixture. This would allow the incorporation of a drug into the matrix prior dissolution into a suitable solvent, or allow the preparation of compositions by intimately mixing different excipients (such as polymers and lipids of different types)

1.2 ...

example 2

Lipid Microparticles (LM)

Materials

[0068]In the examples described below the following materials were tested:

Imwitor 900 (glyceryl monostearate), Condea

Compritol E ATO (glyceryl behenate), Gattefossé

Lutrol E 6000 (PEG 6000), Basf

[0069]Gelucire 50 / 13 (Stearoyl Macrogol glyceride: mixture of mono-, di- and triglycerides and mono- and di-fatty acid esters of polyethylene glycol), Gattefossë

[0070]2.1 Preparation of LM with the Capillary Flow Nozzle Using two Different Nozzle Sizes

[0071]200 g of Imwitor 900 were melted in a thermostated water bath (75° C.), poured into the feeding vessel and processed at the following process conditions:

Product nozzle Ø0.12 and 0.25 mmL CO2 nozzle Ø0.25 mmProduct nozzle115° C.temperatureOven temperature90° C.Gaseous CO2 pressure in2 barthe feeding vesselL CO2 pressureabout 60 bar

Replicates were performed, and the results of the particle size analysis are shown in FIG. 4. The particle size was also verified by optical microscope.

2.2 Preparation of Imwitor ...

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Abstract

A process and an apparatus for the rapid cooling and atomization of liquid or pasty substances, in particular even relatively small amounts of liquid or pasty substances being able to be cooled and atomized economically. Both process and apparatus are particularly useful in the pharmaceutical industry for preparing injectable microparticles of polymer or lipid matrices suitable for the incorporation of active ingredients.

Description

FIELD OF THE INVENTION [0001]The invention relates to a process and an apparatus for cooling and atomizing liquid or pasty substances.BACKGROUND OF THE INVENTION [0002]Cooling processes are used to modify certain properties of substances. The substances to be cooled are generally treated in apparatuses whose cooling action is based on heat-transfer processes between coolant and the substance to be cooled at cooling surfaces. The heat or cold transport between coolant and the substance to be cooled is therefore only indirect. A relatively rapid cooling of the substances, which is very frequently required, cannot be achieved by this means. These cooling processes are also frequently unsuitable for carrying out crystallization or freezing, since insulating deposits form on the cooling surfaces which can impair the cooling process. Cooling processes of this type are, for example, described in Römpp Chemielexikon (Chemistry lexicon) and Pahlmann, Taschenbuch der Kältetechnik (Refrigerati...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): F25D17/02F25D17/00B01J2/04F25C1/00F25D3/10
CPCB01J2/04F25D3/10F25C1/00
Inventor MAIO, MARIOCHICCO, DANIELADONATI, LUCAESPOSITO, PIERANDREAGALLI, LEONARDOMENEGOLI, MAURO
Owner MERCK SERONO SA
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