HU186442B - Process for treating surface of different cristals with fluidization - Google Patents

Abstract

The present invention relates to a process for the preparation of homogeneous crystalline and surface-shaped particles for the preparation of medicaments by treating particles having different crystalline forms and surfaces present in an alcoholic or aqueous dispersion medium with a fluidization technique, at a dispersion rate of from 0.1 to 4 1 / min. clock fluidizing air velocity at 4 bar dust pressure. 185142 -1-

Description

The present invention relates to a process for forming crystalline surfaces by fluidization. The process according to the invention is particularly important in pharmaceutical technology for the preparation of tablets and dragees.

The essence of the process is to dissolve the surface of crystals unsuitable for tabletting and dragee nucleating with a suitable solvent at such a rate and extent that the original shape or surface, due to the collision of the particles, takes up a shape suitable for further use. The conditions and parameters required for the operation can be provided in a fluidization device.

Fluidization technology is widely used in the pharmaceutical industry for volumetric thickener, dragee, bark granulation, and the procedures are known from manuals.

The use of fluidization to form crystalline surfaces has not yet been described in the literature.

In the field of pharmaceuticals, it is essential to ensure that products of the same quality are reproduced. In order to achieve this with the exact respect of the production technology requirements, it is important to observe the quality standards of the materials used. One important criterion for quality requirements is the same crystal form. The process of the present invention utilizes fluidization technology prior to further drug processing of the various surface crystals, such as tabletting and preparation of dragee cores. This technology is also followed for surface treatment of materials where granulation is not required, only the crystalline shape is desired.

Prior to our process, the material consisting of very different crystals is dispersed and comminuted with a suitable silk screen, granulating apparatus. Hereafter, the drug formulation problem is caused by the shape and surface of the particles.

The process according to the invention relates to the shape and surface of tablets and dragee cores.

In the process, a solvent is selected which dissolves the crystals well, taking into account the flammability, environmental impact, and economics of the solvent, and spraying the solvent into the fluidization system with the n parameters required. The inlet air temperature is preferably 30 ^e C, since this ensures every season and so the parameters concretize. At this temperature, evaporation and the amount of solvent to be used are also lower than at higher temperatures. The temperature used is also favorable for thermosensitive materials. The solvent dissolves on the crystal surfaces without liquefying the material. The optimum amount and time of solvent used and the mechanical action of the particles on each other - collisions - greatly alter the surface and shape of the crystals, making them usable. The quantity and quality of the solvent may vary from material to material. In the process, binders may be introduced into the system in addition to the crystals. Preferably, the binder is dissolved in the required amount and consistency of the solvent to be used.

The present invention therefore relates to a process for the preparation of pharmaceutical particles of homogeneous crystalline form and surface, and to the preparation of tablets and / or dragee cores thereof by spraying particles of different crystalline forms and surfaces in a dispersion medium with a fluidization technique. At a fluidizing air velocity of 1000-5000 m ³ / h at a pressure of 4 bar and the resulting homogeneous particles are compressed into tablets or dragee cores. Advantages of the process according to the invention are that it is possible to eliminate the false crystallization process, which results in a material salt and makes the preparation of the composition very expensive and time consuming. The operation is carried out in an automated, continuous closed system and the process can be easily integrated into the process line during tableting and dragee-making operations. A further advantage is that the granules of the process contain a greater number of solid crystals than the agglomerates, which in some cases may provide a blistering effect. The process makes various polymorphs suitable for tabletting.

The advantages of our procedure are demonstrated by the following data.

Grain size distribution of granules containing α-diethylaininoacel-2,6-xylidide (lidocaine) by sieve analysis:

-2IfíMJJ

Lidocaine granules made of crystallized material without surface treatment Lidocaine is a granulate made from a commercial powder, not recrystallized material, after surface treatment Below 32 μ m - - 32 pm - 63 pm 2% 2% 63 pm - 90 pm 2% 2% 90 pm - 125 pm 2% 2% 125 pm - 250 pm 10% 10% 250 pm - 500 pm 44% 32% 500 pm - 1000 pm 39% 51% Above 1000 pm 1% 1% Moisture content: 1.3% 1.5% Weight capacity loose (SL): 2.3 ml / g 1.9 ml / g Weight Volume Solid (ST): 2.0 ml / g 1.6 ml / g Sieve analysis: Lidocaine raw material Lidocaine raw material crystalline powder commercial powder after recrystallization without recrystallization without surface treatment without surface treatment Under 32 pm 6% - 32 pm - 63 pm 75% 2% 63 pm - 90 pm 15% 4% 90 pn - 125 pm 3% 3% 125 pm - 250 pm 1% 11% 250 pm - 500 pm - 44% 500 pm - 1000 pm - 32% Above 1000 pm - 4% Moisture content: 0.3% 0.4% Weight Volume Loose (SL): 3.0 ml / g 1.8 ml / g Weight Weight Compact (ST): 2.2 ml / g 1.6 ml / g

Dragees made from fluidized granules and conventional (kneading)

GOK OBSERVATION. Fluid, cross it. material Fluid, surface treated material Gyúrásos recrystallization. material Tensile strength 5-6 kg 5-6 kg 4-6 kg Disintegration time 6-8 minutes 8-10 minutes 5-8 minutes Fria billiards 0.3% 0.4% 0.4% Diameter 12 mm 12 mm 12 mm Form lens lens lens average Weight 0.40g 0.40g 0.40g

The process is applicable in all cases where the crystalline form interferes with the drug formulation operation or operations, such as, for example, also for d, 5-ethyl-5-isopentyl-barbituric acid.

Figure 1 shows the distribution of granules, starting materials, recrystallization materials and fluid after surface treatment of grains.

It can be seen that completely different starting materials can be used to produce granules of nearly the same size. The lidocaine crystals before and after fluid surface treatment are illustrated by scanning electromicroscopes 1 and 2.

Shot 1 shows the original, irregularly shaped lidocaine crystals with rough surfaces and corners. The

1HC112

P, such materials, during dust technology operations - mixing, sieving - easily break and cause dust explosions.

Snapshot 2 shows the surface-treated, well-rounded crystals with rounded edges. 5 ós 2 3. Fig. 3 with fluid surface treatment then. the subsequent compression of tablets, dragee cores, breaking strength and disintegration! he spent his time on recrystallization tablets made by kneading technology 10 and the excipients in the formulation of the outer phase.

The following is a non-limiting example of our procedure: 15

l. Example 1 Preparation of a Dragee Core containing α-Diethylaminoacel-2,6-Xylidide 20

25 kg of lidocaine base, 1.6 kg of lactose, 1.8 kg of potato starch and 0.09 kg of 25 Esma spreng (formaldehyde casein) are weighed into the fluid container. The materials are homogenized and transferred to the fluidization system using 7.5-8 L of ethyl alcohol as solvent or dispersion medium. 30

The fluidization parameters are as follows: Fluidizing air velocity: 500-1000 m ³ / h Dosing rate: 400 ml / min Inlet air temperature: 30 'C. Atomisation pressure: 4 bar. 35

Outlet air temperature: 36-38 'C.

The resulting material is granulated with a solution of the following composition:

Gelatin Gold: 0.28 kg

Polyvinyl acetate (Mowilith DH 50%): 8.66 kg 40

The granulating materials are made up to 26 L with deionized water.

Granules of non-recrystallized material with surface treatment:

sieve analyzes 32 μηι - 32 μ m - 63 μ in announced 2% 63 μ in - 90 μ in between 2% 90 μm - 125 μ πι between 2% 125 μ m - 250 μ κι between 10% 250 μ ni - 500 μπι közölt32% 500 μπι - 1000 μπι kózölt51% 1000 μ ni - 1000 μ ιιι between 1% The granules

moisture content: 1.5% by volume (loose): 1.9 ml / g by volume (solid): 1.6 ml / g After drying the granules with 0.2 kg of silica, 0.26 kg of niagnium stearate, 0.4 kg of talc and kg of microcrystalline cellulose and pressed into a dragee core.

Breaking strength: 5 - 6 kg

Disintegration time: 8-10 minutes

Friability: 0.4%

Diameter: 12 nini

Shape: lens

Weight: 0.40 g

Claims (3)

CLAIMS 1. A process for the preparation of pharmaceutical particles of homogeneous crystalline form and surface, wherein the particles having different crystalline phosphorus present in an alcoholic or aqueous dispersion medium are surface-treated by fluidization techniques at a rate of 0.14 1 / min dispersion, air velocity at 4 bar spray pressure. 2. The process of claim 1, wherein the <RTI ID = 0.0> c-dieLylaminoacet-2,6-xylidide </RTI> crystals are surface treated. 3 drawings The Director of Economic and Legal Publishing is responsible for the publication 87.2507.66-4 Alföldi Nyomda Debrecen - Chief Executive Officer: István Benkő Chief Executive Officer