CS214499B1 - Process for preparing pharmaceutical microcrystalline cellulose - Google Patents

Abstract

The invention provides a solution for the preparation of microcrystalline cellulose, which has use in the pharmaceutical industry. The essence of the invention is that the microcrystalline cellulose obtained by acid heterogeneous hydrolysis of native cellulose is subjected to wet defibration after hydrolysis, and in the second stage the defibrated microcrystalline cellulose is filtered off and dried, and in the third stage the dried microcrystalline cellulose is defibrated and finally the defibrated product is fractionated. The invention is used in the pharmaceutical industry for dry tableting of medicines and in the food industry for the preparation of mayonnaise, puddings, ice cream and other food products.

Description

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Process for preparing pharmaceutical microcrystalline cellulose

The present invention provides a process for the preparation of microcrystalline cellulose for use in the pharmaceutical industry.

SUMMARY OF THE INVENTION The microcrystalline cellulose obtained by acid heterogeneous hydrolysis of native celluloses is subjected to wet defibrating after hydrolysis and the second-stage defibrated microcrystalline cellulose is filtered and dried, and in the third stage the dried microcrystalline cellulose is defibrated and finally the defibrillated product is fractionated.

The invention has utility in the pharmaceutical industry for dry tableting of medicaments and in the food industry for the preparation of mayonnaise, puddings, ice cream and other food products.

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The invention relates to a process for the preparation of microcrystalline cellulose suitable for use in the pharmaceutical industry.

Microcrystalline cellulose, which is prepared by known methods by acid heterogeneous hydrolysis of native celluloses (U.S. Pat. No. 8,978,446, Sel. U.S. Pat. No. 8,232,508, PV 8253-80), is not suitable for direct use in the pharmaceutical industry. It is due to its inadequate chemical and physico-colloidal properties. So eg. poor chemical purity (high content of heavy metals, extractives and acid degradation products of mono and oligosaccharides).

The more violent deficiency of the microcrystalline cellulose obtained after acid hydrolysis of the native cellulose raw materials is not suitable for the shape and size of the particles. Depending on the type of oellulose raw material, the microcrystalline cellulose particles are rod-shaped of varying length and thickness, the length being several times higher than the particle thickness. This is disadvantageous from the viewpoint of the rheological properties of the microcrystalline cellulose, since uniform granulation of the granulate on the tablet machine is not ensured during tabletting, in particular of the dry granulate.

This drawback is particularly pronounced today because the current tableting machines flow at high speeds of at least 80 to 100,000 tablets per hour. In the case of these pseudopathies, the rheological properties of the local cellulose microcrystals used in direct tablet drying must be particularly good.

The above-mentioned drawbacks and the fulfillment of the high demands on the multifaceted quality requirements of microcrystalline cellulose suitable for the preparation of tablet formulations of many drugs by direct tabletting of the dry granulate are solved by the new application of the invention.

SUMMARY OF THE INVENTION The microcrystalline cellulose obtained by the known method by acid heterogeneous hydrolysis of native celluloses is subjected to a wet defibral in a flour-mixer at a speed of 6 to 10 ths / min for 10 to 30 minutes in water, at a cellulose concentration of 10 to 20%. %, whereby in the second stage the deflected microcrystalline oellulose is filtered preferably onto a salt filter and dried at 80 to 100 ° C and in the third stage the dried microcrystalline cellulose is defibrated on a dry deflector preferably on a disc defibrator and finally defibrated to fractionated product. a screening device, preferably a sieve for fractions with a size often in the range of 30 to 300 microns.

For the production of the pharmaoeutic microcrystalline cellulose, it is suitable to start from microcrystals4.

talc hydrolyzed to a higher polymerization stage, ranging from 150 to 250 DP. This gives wet defibral products which, after drying, have a more advantageous distribution of particle sizes (30 to 350) in view of the rheological properties required for spraying the dry granulate on a tablet machine. If microcrystalline oellulose with a polymerization degree below 150 DP were used, the distribution of the part in the finished product is shifted to a range of 20 to 80%, which is less advantageous in the case of dry tableting of pharmaceutical preparators.

Microcrystalline oelulose intended for pharmaceutical application must be of high purity chemically. Particularly, the unsatisfactory criteria are in particular for the content of heavy metals which catalyze the decomposition of many pharmaceutically effective preparers. The heavy metal content should not exceed 10 to

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The correct particle size distribution of the finished product is achieved by selecting the correct degree of wet defibrillation. Normally, a defibrillation time of 10 to 20 minutes is sufficient, depending on the type of industrial wet mixer, the number of turns, and the cellulose concentration of the defibrillator.

By wet defibrating, microcrystalline cellulose fibrilizes, swells considerably, and most importantly, geometry changes frequently. From the rod shape, particles are formed in which the diameter increases frequently at the expense of the particle length. The resulting product after drying and dry defibrating to a more advantageous particle geometry, which underlies the good rheological properties of the product during tabletting.

The product after dry defibrillation has a very wide particle distribution, ranging from 20 to 500, so it is necessary to include the particle fractionation using a sieve tracer at the end of the production process. Fractions having a particle size of 30 to 250 are most often required for the pharmaceutical industry, but fractions below 30 and above 250 are also used for special purposes.

An important factor is the requirement for proper drying of the product. The optimum moisture content of the dried product is between 3 and 5% gaps in order to suppress the electrostatic properties of the particles most.

The advantage of the proposed process for the preparation of microcrystalline cellulose is that:

- does not require complex technological equipment,

it does not produce any waste water and therefore the production is environmentally sound,

- is energy-intensive,

- allows menif to a wide extent. Theological properties of dry product,

- allows to extend the spectrum of applicability of microcrystalline cellulose, especially in the pharmaceutical industry and human medicine.

Examples

Example 1

150 g of 240 DP microcrystalline cellulose prepared by acid heterogeneous hydrolysis of kraft beech pulp is mixed with 1000 ml of water in a mixer at a speed of 8 to 10 thousand / minute for 15 minutes. The defibrated microcrystalline cellulose is then filtered off, dried and the dried granulate defibrated on a dry defibrator. The defibrated product is fractionated on a sieve screen to the desired particle size. The fraction with a range of 30 to 300 reaches 60 to 65% and the fraction with a fraction below 30 to 30 to 40%. However, with a size of between 30 and 300, it has very good theological properties and is suitable for direct tabletting in a dry manner. The iron content is less than 15 ppm.

Example 2

The process of Example 1, except that the microcrystalline cellulose has a polymerization degree of 165 DP and the wet defibrations take place for 10 minutes. The fraction with a particle size fraction of 30 to 350 is 50 to 55% and the fraction with a large fraction below 30 is 45 to 50%.

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Example 3

The procedure of Example 1 was followed except that the wet defibrations were at a speed of 6,000 rpm. for 20 minutes. The resulting product has a similar particle distribution as in Example 1 ·

The invention has wide application in the pharmaceutical industry for the dry tableting of medicaments used in the food industry for the preparation of mayonnaise, puddings, ice cream and other food products.

Claims (1)

Example 3 The procedure of Example 1, except that the wet defibrillation occurs at a de-fibrator speed of 6,000 rpm. for 20 minutes. The resultant product has a similar particle distribution to that of Example 1. The invention has wide application in the pharmaceutical industry for the dry tableting of pharmaceuticals in the food industry for the preparation of mayonnaises, puddings, ice cream and other food products. OBJECT OF THE INVENTION A process for preparing a pharmaceutical microcrystalline cellulose by acidic heterogeneous hydrolysis of native celluloses, characterized in that the microcrystalline cellulose is subjected to a hydrophilic wet defibrillation in a high-speed mixer at a speed of 6 to 10 thousand / minute for 10 to 30 minutes in water at a cellulose concentration in in the second stage, the defibrated microcrystalline cellulose is preferably filtered on suction filters, dried at 80 DEG to 100 DEG C., and in a three-tier stage, the dried microcrystalline cellulose is dried on a dry defibrator, preferably on a disk defibrator, and finally the defibrated product fractionates on a screening apparatus preferably a sieve sorter to a particle size fraction of 30 to 300. Printed by Moravské tiskařské závody, provoz 12, Leninova 21, Olomouc Price: 2,40 Kčs