HU193220B - Process for regenerating methylene-chloride, alkohol or aceton from mother lyes of oral kompositions - Google Patents

Abstract

Industrial wastes contg. methylene-chloride, methanol, ethanol, acetone or other water-miscible organic solvents are rendered harmless and the valuable waste prods. are recovered by mixing the waste with the 1-5 fold vol. of a 2-10 vol.%, pref. 5 vol.% aq. sodium-carbonate soln. and sepg. the settled phases. The methylene-chloride phase is treated with conc. sulphuric-acid, de-acidified and opt. purified by distn. The solvent phase is concentrated and purified in the usual way by distn. The recovered methylene-chloride and the organic solvents are of adequate purity for industrial applications.

Description

The present invention relates to a process for recovering methylene chloride, alcohol or acetone from the mother liquor formed in the formulation of oral pharmaceutical compositions.

In the pharmaceutical and chemical industries, methylene chloride and methylene chloride and various solvents are widely used in the manufacture of raw materials and pharmaceutical formulations, e.g. methanol, ethanol, mixtures containing acetone. In this case, large volumes of solvent mixtures are formed which cannot be discharged directly into the sewer due to environmental regulations. Such hazardous wastes include, but are not limited to, residues of the paint coating agent used during the tablet manufacturing process to form the outer layer of the tab coat, the coating coating agent used in microencapsulation with the washing liquid, its solvent and washing liquids. In the pharmaceutical industry, solvents for lacquer coatings used in gastric acid-resistant pharmaceutical formulations are mixed in various ratios of methylene chloride / methanol, methylene chloride / ethanol, methylene chloride / acetone in a ratio of 1: 9 to 9: 1 by volume.

It is known that methylene chloride can be combined with water and methanol, respectively. forms an azeotropic mixture with ethanol. (Azeotropic Data, Advances in Chemistry Series 6, American Chemical Society, Washington, 1952, p.22). The methylene chloride also gives an azeotropic mixture of acetone, the azeotropic containing 30% of acetone, boiling at 57.6 ° C. . Further literature (Bruckner Gy. Organic Chemistry I, 271.0) discloses that methylene chloride is used to decontaminate ethanol because the ethanol / water / methylene chloride mixture gives a ternary azeotrope.

With regard to the properties of methylene chloride (Porter's Organic Chemical Analytical Pocket Book, Technical K.K. 1966, p. 861), it has been found that methylene chloride, like chloroform, is converted into losgene by impurities which slowly hydrolyze to carbonic and hydrochloric acid.

It is an object of the present invention to provide a process for the economical processing of methylene chloride-containing mother liquors from tablet manufacturing and microcapsulation to recover methylene chloride on the one hand and alcohols or acetone on the other hand.

The recovery of methylene chloride is water and water-miscible solvents, e.g. methylene chloride / water degradation products (phosgene + hydrochloric acid), methylene chloride / acetone, methylene chloride / methanol, methylene chloride / ethanol, etc. up to now, direct distillation, freezing or sedimentation of its mixtures was not feasible.

In further experiments, it has been found that methylene chloride-containing mother liquors can be used to produce methylene chloride and the solvent which is the other component of the mixture in good commercial quality.

The object of the present invention is to add an aqueous sodium carbonate solution to the methylene chloride-containing industrial mother liquor, mix the mixture and add an equal volume of tap water to the volume of the impurity solvent component. The components of the phase system can be separated by settling, the lower phase being methylene chloride and the upper phase being the aqueous alcoholic acetone phase. The methylene chloride and the aqueous solvent were drained separately, and concentrated sulfuric acid (about 0.02-0.1% v / v) was added to the methylene chloride and the methylene chloride was separated again by suction, The mixture was acidified with solid sodium carbonate (1: 1) and filtered. The methylene chloride thus obtained can be purified by distillation in an industrial grade, if necessary by conventional means.

The aqueous / solvent phase can also be concentrated by distillation as needed.

The following examples serve to carry out the process of the present invention without limiting it to the process.

Example 1

100 ml of the mother liquor from the manufacture of erythromycin granules, consisting of 45% methylene chloride, 45% methanol and 10% by-product of the chemical reactions during manufacture, is made up of a 250 ml we measured. To the mixture was added with stirring 50 ml of 5% aqueous sodium carbonate solution at 5 ° C. The mixture was stirred for 20 minutes, ensuring that the temperature did not rise above 20 ° C. Then enough! the precipitated solid impurities are removed by filtration so that the filtrate is collected in a separatory funnel. After 15 minutes in the separatory funnel, the styrene was separated into two phases, and the aqueous-alcoholic portion was separated from the methylene chloride. Methylene chloride was at the bottom, and the aqueous-alcoholic phase was at the top.

In the following, the two phases are processed separately.

a. / The resulting 42 ml of methylene chloride phase was poured into a round-bottomed flask and 2.5 ml of concentrated sulfuric acid was added dropwise with stirring at a temperature below 20 ° C. After stirring for 15 minutes, the sulfuric acid portion was settled, separated and repeated. To methylene chloride, carefully separated from the sulfuric acid, was added 5 g of anhydrous sodium carbonate, followed by stirring for 2 hours and assaying the acidity of methylene chloride (Dr. Ed. Kolos, Chemical Research, Budapest, 1969, p. 430-1). When a free acid content of 0.0005% was reached, the methylene chloride was separated from the sodium carbonate and distilled. The amount of methylene chloride thus obtained was 41 ml.

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Density: 1.325 g / cm ³ Boiling point: 40-41 ° C Water content: 0.1%

Distillation residue: 0,002% vol Free acidic content: 0,0005% vol

Yield: 95%.

b. / The resulting 100 ml of methanolic phase was transferred to a 250 ml standard-ground distiller fitted with a Vigreux column, ball-type cooler and distilled. Until the temperature of the vapor phase stabilized, 5% of the original volume was collected, and the main distillate was collected at a boiling point within the temperature range of 1 ° C, which was about 35% of the initial volume. Beyond the boiling point, distillation was carried out to a head temperature of 98 ° C, which was about 30% of the initial volume. The pre- and post-distillates were used for the next processing, taking into account the water content. The sulfuric acid formed during the process is used for the first sulfurization of the next processing. Sulfuric acid from the second sulfuric acid treatment is neutralized with contaminated sodium carbonate formed during processing. The amount of crude methanol was 35 ml.

Density: 0.792

Boiling point: 64.5 ° C

Yield: 95%

Example 2

100 ml of the solvent mixture formed during the manufacture of the Voltaren tablet, containing about 70% methylene chloride, 10% methanol and 20% water and by-products formed during the manufacture, were weighed into a round-bottom flask described in Example 1. To the mixture was added with stirring 20 ml of 5% aqueous sodium carbonate solution at 5 ° C. The mixture was stirred for 20 minutes, making sure that the temperature did not rise above 20 ° C. The solid impurities formed from the mixture are then removed by filtration by collecting the filtrate in a separatory funnel. After 15 minutes in the separatory funnel, the filtrate switched to two phases and the methylene chloride was separated from the aqueous methanol. The aqueous methanol phase was collected for work up and methylene chloride was worked up as follows. The resulting methylene chloride phase (67 mL) was poured into a round-bottomed flask and 3.25 mL of concentrated sulfuric acid was added dropwise with stirring at a temperature below 20 ° C. After stirring for 15 minutes, the mixture was settled, the sulfuric acid was separated off, and the operation was repeated. To the methylene chloride separated from the sulfuric acid was added 7.5 g of anhydrous sodium carbonate, and after stirring for 2 hours, the acidity of the methylene chloride was tested by the method of Dr. Kolos. When a free acid content of 0.0005% was reached, the methylene chloride was separated from the sodium carbonate and distilled under atmospheric conditions. The amount of methylene chloride thus obtained was 65 ml.

Density: 1.327 (at 18 ° C)

Boiling point: 40-41.5 ° C

Water content: 0.12%

Distillation residue: 0.002%

Free acidity: 0,0005%

Yield: 95%.

Example 3

The approx. 50 ml of methylene chloride, 40% of acetone and about 10% of the mother liquor containing the by-product or impurity were weighed into a round bottom flask of Example 1. To the mixture was added with stirring 40 ml of 5% aqueous sodium carbonate solution at 5 ° C. The mixture was stirred for 20 minutes, making sure that the temperature did not rise above 20 ° C. The mixture was then filtered and collected in a separatory funnel. In a separatory funnel, the filtrate switched to two phases and after 15 minutes the methylene chloride was separated from the aqueous aceonone phase. In the following, the two phases are processed separately.

the. The resulting 49 ml of methylene chloride phase was poured into a round-bottomed flask and 2.9 ml of concentrated sulfuric acid was added dropwise with stirring at such a rate that the temperature remained below 20 ° C. After stirring for 15 minutes, the sulfuric acid portion was separated and the operation was repeated. 5.8 g of anhydrous sodium carbonate were added to the separated ethylene chloride from the sulfuric acid, and after stirring for 2 hours, the acidity of the methylene chloride was tested by the method of Dr. Kolos. After reaching 0.0005% free acid, it was separated from the sodium carbonate and distilled off under atmospheric conditions. The amount of methylene chloride thus obtained was 47 ml. Density: 1.325 (at 18 ° C)

Boiling point: 40-41.5 ° C

Water content: 0.12%

Distillation residue: 0.002%

Free acidity: 0,0005%

Yield: 95%.

b. The resulting 90 mL aqueous acetone phase was subjected to a 250 mL standard-ground distillation with a Vigreux column, ball-cooled. Until the temperature of the vapor phase stabilized, about 5% of the initial volume was collected, and the main distillate was collected at a boiling point at a temperature of 2 ° C, which was about 5% of the initial volume. 30%. Beyond the boiling point, distillation was carried out to a head temperature of 92 ° C, which was approx. It was 20%. The pre- and post-distillates were used for the next processing, taking into account the water content. The amount of acetone thus obtained was 27 ml.

Density: 0.792 (20 ° C)

Boiling point 55.2-57.2 ° C

Water content: 0.3% by weight alkalinity: none

Acidity: 0.002% w / w 3

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Distillation residue: 0.002%

Yield: 98%.

Claims (1)

A process for treating mother liquors formed during the formulation of oral formulations containing methylene chloride and alcohol or 5 acetone by settling the solvents, followed by chemical purification and then distillation, characterized in that ² volumes of alcohol or acetone an aqueous solution of sodium carbonate (2 to 10% by weight, preferably 5% by volume) is added, and the phases are then separated by settling at ambient temperature, followed by separation of the phase containing methylene chloride in an amount of 0.02 It is treated with 0.1 times 98% sulfuric acid, filtered after settling, de-acidified with at least an equivalent amount of the sulfuric acid added and subsequently filtered, optionally by distillation in known manner, while the aqueous, alcohol or acetone containing f Purification of the purified acetone or alcohol from the aase is known per se.