CS230855B1 - The way to determine the safety of rubber bays in health care - Google Patents

Abstract

The invention provides a method for determining the safety of rubber stoppers in healthcare in a glucose solution with a concentration of 5% to 40% w/v. The essence of the invention is characterized in that in a glucose solution with a concentration of 5% to 40% w/v. After the stopper is brought into contact with this solution for 30 minutes at a temperature of 120 °C at a pressure of 0.101 325 MPa and at least 24 hours after cooling, the appearance of the solution, the appearance of the stopper, the current acidity, conductivity, foreign organic impurities are determined spectrophotometrically in the wavelength range of 220 to 360 nm, a purity test is performed for arsenic, barium, borates, aluminum, magnesium, heavy metals in two ways, titanium, calcium, strontium, zinc, iron, chlorides, phosphates, sulfates, sulfides, hydrogen sulfides, thiosulfates and a quantitative determination of glucose.

Description

230855

SUMMARY OF THE INVENTION The present invention provides a method for determining the health safety of rubber stoppers in a glucose solution at a concentration of 5% to 40% w / v.

The method of determining the safety of rubber mats in health care on model solutions according to CSN 62 1156 - Non-toxic rubber testing has proven to be unsatisfactory and remote from practice. It is necessary to approximate the test solutions to model solutions which characterize a part of a wide range of infusion solutions and are basically simple solutions to be able to judge the high quality of the solution itself, as well as the packaging material, including the rubber stopper. . CS3 in a glucose monograph requires monitoring for solution, glucose identity, current acidity electrometric testing, solution color concentration according to solution concentration and glucose content determination. ON 86 4423, effective from 1.1.1966, does not require purity tests for glucose infusion solution. Based on experimental results, it has been shown that it is possible to carry out tests on possible migrating components and are described in the description.

SUMMARY OF THE INVENTION It is an object of the present invention to avoid inadequate determination of the safety of rubber plugs in the health sector by contacting the rubber stoppers with a 5% and 40% w / v glucose solution. for 30 minutes at 120 ° C, a pressure of 0.101 325 MPa and at least 24 hours cooling down is determined with respect to the solution, with respect to the stopper, the current acidity, the conductivity, the foreign organic contamination spectrophotometrically at the wavelength range of 220 to 360 nm. test the presence of glucose, test for purity on arsenic, barium, borate, aluminum, magnesium, heavy metals in two coats, titanium, calcium, strontium, zinc, iron, chlorides, phosphates, sulphates, sulphides, acidic sulfides, thiosulphates, and quantitative glucose determinations.

By extending the method of determining the safety of rubber stoppers in the healthcare sector, a glucose solution of 5% (by weight to 40% w / v). to speed up the knowledge of quality gums for direct use in the production of glucose infusion solutions and by determining the conductivity, proven arsenic, barium, borate, aluminum, magnesium, heavy metal two-way, titanium, calcium, strontium, zinc, iron, chlorides, phosphates, sulphates, sulphides, acid oxides, thiosulphates, foreign organic impurities by measuring spectral absorption curves in the wavelength range of 220 to 360 nm and confirming the possibility of using rubber plugs of the infusion solutions containing sugars - nutritional solutions or following the interaction of the plug with made of this type, the possibility of tracking the migrating substances into the solution by confirming the quality of the 4 infusion solution towards the quality of the stopper. Example of execution

The glucose infusion solution is prepared from a subset satisfying the requirements for the preparation of infusion solutions by dissolving in apyrogenic water for injection, satisfying the requirements of the current Pharmacopoeia No. CS3 with the established infusion solution technology. the amount of glucose weighed is dissolved in 1/3 of the desired amount of solvent - boiling water. After cooling to 20 [deg.] C., it is made up to the desired volume with water for injection and is further used in the conventional technology for infusion solutions.

500 ml infusion bottles are well washed, bottle washing technology is matched with the automatic washer program.

The flasks are soaked for 24 hours in degreasing solution of sodium phosphate (30 g / L) and chloramine BS (5 g / L) for degreasing and disinfection, after which the bottles are washed well in running water for about 1.5 minutes and more. Wash for 5 minutes in hot water at 80 ° C, rinse the flasks with a neutralizing solution of vitronic acid (20 g / L), rinse for 1.5 minutes with cold drinking water for 1.5 minutes and pyrogen-free water so that After thoroughly washing, the bottles are sterilized for 120 minutes at 180 [deg.] C. with hot air, after completion of the sterilization, the bottles are filled with the prepared solution with 400 ml of glucose solution and the stopper with good washed stoppers. that the sagum plugs thoroughly wash under running water to remove surface particles and coarse debris, soak the Dubaryl detergent degreaser (or else suitable for this purpose (5 g / L), then pour the distilled water into the stoppers 4X, distilled water 2X, then pour distilled water and stopper for 10 minutes, the water rinses and rinses 3X in pyrogen-free water. -do. The pyrogen-free water is poured onto the stoppers and sterilized at 120 ° C for 30 minutes. Cooling the pyrogen-free water from the coves and stoppers is ready for plugging the bottles.

After filling and stopping the flasks, the flasks are sterilized at 120 ° C for 30 minutes down the neck. Simultaneously, under the same conditions, a blank sample is prepared as a comparison sample in the sample.

After sterilization, the solutions are allowed to cool and after 24 hours the tests are carried out.

Under the same technological conditions, the solution may also be concentrated to sterilize 3 plugs of a submerged glucose sample. At the same time, the reference solution is prepared without stopper, under the same conditions as the stoppers. The glucose flow assay is as follows: 5 8 1. Solution appearance - The change in clarity, color, odor, and mechanical impurities is monitored against the reference solution. 2. The appearance of the stopper - the change in plug after sterilization is monitored, puncture ability, fragmentation, tackiness, puncture tightness, and the like. 3. Acidic acidity - the pH of the solution is electrometric at a suitable pH, S, the difference measured in the test solution and the solution compared. 4. Conductivity - is measured on a suitable meter. The measured value is nssmall higher in the test solution than the reference solution. 5. Foreign Organic Pollutants - The spectral absorption curve is measured in the wavelength range of 220-350 nm for 10 min.

The shift of the sample and the reference solution is monitored.

IDENTIFICATION TESTS 6. Glucose - 5.0 ml of the test solution is boiled with an equal volume of Fehlin reagent, an orange-red powder precipitate is produced (reducing saccharides) Preparation of Fehling's reagent 7 g of copper sulphate are dissolved in water and added to 100 ml, even JI. 35 g of potassium sodium tartrate and 10 g of potassium hydroxide are dissolved in water and added to 100 ml. Prior to use, the same volumes of solutions are mixed.

Tests for purity 7. Arsenic - is tested according to the proposal of general statute for CsL4 as follows:

Pipette 20,0 ml of the test solution into a flask of the arsenic reagent, add 0,5 ml of fuming hydrochloric acid, free of arsenic, 2,0 ml of potassium iodide solution (150 g / l) and 0,5 ml of stannous chloride solution The mixture is mixed well and allowed to stand for 15 minutes to reduce the arsenic compounds to arsenic when present, while impregnated impregnated inserts into the glass tube connecting the two parts of the apparatus. with a lead acetate solution (100 g / L) to collect sulfuric acid and absorbent, the tubes were measured with 3.0 ml of a pyridine solution of diethylaododithiocarbonate, then 3.0 grams of granular zinc, free of arsenic and flasks were immediately introduced into the instrument. the apparatus is closed by attachment, the hydrogen escaping is passed through the absorption tube for up to 60 minutes. If the flow rate of hydrogen is weakened, a further portion of fuming hydrochloric acid, free of arsenic, is added to the funnel of the machine, and a small amount of tin (II) chloride is added to activate the zinc.

A comparative solution test is also performed. The silver pyridine solution of diethylamide dihydrogen thiosulphite must not be crosslinked more intensively with the test solution than in the comparative solution for the preparation of a pyridine solution of silver dihylamide dithiocarbonate. 0.5 g of silver diethylamide di-sodium bicarbonate (CsHsbNCS.SAg is dissolved in freshly distilled pyridine per 100 ml of solution, filtered to a dry darkened stoppered stopper. The solution is stable for about 2 weeks. 8. Barium, strontium - test - Semi-dry rubber test in aqueous extract followed by: Add 0.20 ml of dilute sulfuric acid solution (509 g / L) to 0.5 ml of the test solution. as a comparative solution under the same conditions 9. Borates - Tested according to the method for testing rubber caps in the health sector as follows: To 0.5 ml of the test solution add 1.0 ml of dilute hydrochloric acid solution (10 g / L). Also, a comparative solution is prepared. The curcuma paper dripped with the sample solution must not stain more intensely than paper. 10 .... Aluminum - the methods to be tested for the rubber test tubes in the healthcare sector are as follows: Add 0.2 ml of ammonium acetate (10 g / L) to 0.5 ml of the test sample. and 0.2 ml of aurintricarboxylic acid aluininone-ammonium salt solution, but tetretraoxiflavinol (1.0 g / L), and 23087 of 0.5 ml of saturated carbonate ammonium solution (1 µm) can be added.

The test solution must not become more intense than the reference solution under the same conditions. 11. Heavy metals - is tested according to the general principle for CSL4. and II. as follows:

Method I. — To 10.0 mL of the test solution is added 0.5 g of ammonium chloride and, after dissolution, 1 drop of dilute ammonia solution (100 g / L), 3 drops of sodium sulfide and stirred. Within 2 minutes after the addition of sodium sulphide, the test solution must not be faded into hydrogen peroxide. Test solution under the same conditions.

Spósob II. To a further 10.0 mL of the test solution was added 1.0 mL of dilute acetic acid solution (60 mL / L), 2.0 mL of hydrogen sulfide, and stirred.

Within 5 minutes of the addition of hydrogen sulphide, the test solution must not be more intense than the reference solution under the same conditions. 13. Titanium - The method modified by the method for testing rubber mats in the medical field as follows: 5.0 ml of the test solution is acidified with 2.0 ml of dilute sulfuric acid solution (100 g / L) and 5.0 ml is added. ml of hydrogen peroxide solution. The solution to be tested must not stain more intensively and with a comparative solution under the same conditions. (Positive reaction can show 0.01 milligrams of titanium, the reaction is abolished by Cr aFe] 14. Calcium and strontium - The general formula proposal for CS4 is tested as follows: To 10.0 ml of the test solution add dilute ammonium hydroxide solution to basic reaction. , 2.0 ml of ammonium oxalate solution and thoroughly mixed.

Within 15 minutes after addition of the ammonium oxalate, the test solution must not be more intense than the reference solution under the same conditions. 15. Zinc - The Compendiummedicamentorum Water Extract Stage is tested as follows: 10.0 ml of the test solution must not be hardened more intensely than the reference solution under the same conditions by adding 10 drops of potassium potassium cyanate (50 g / L) solution. 16. Iron - The method of testing for the rubber test tubes in the health sector is as follows: To 10.0 ml of the test solution is added all K2S2O3 persulfate crystals, a few drops of dilute hydrochloric acid solution] and is heated. sodium chloride solution NaCNS, the solution should not turn red more intensely than the reference sample under the same conditions 17. Chlorides - the stage of the general draft for CS4 is tested as follows: 10.0 ml of the test solution is acidified with 1.0 ml of the diluted solution sulfuric acid], add 3 drops of silver nitrate solution c (AgNo3) = 0.1 mol / L, shake vigorously .

Within 5 minutes the test solution must not be paled more intensely than the reference solution under the same conditions. 18. Phosphates - Tested according to a method adapted for the testing of medical bay bays as follows:

10.0 ml of the test solution is pipetted into a 25 ml Erlenmeyer flask for metal tin, a few crystals of sodium chloride and 5 drops of ammonium molybdate solution are added. The test sample of Sanesmia should be more intensely blue than the reference solution under the same conditions. Preparation of ammonium molybdate solution in sulfuric acid] 2.0 g of ammonium molybdate is dissolved in 20 ml of water and poured onto 60 ml of dilute sulfuric acid solution (500 g / L). 19. Sulphates - test the general draft stage for Cs4 4 as follows: To 10.0 ml of the test solution add 0.5 ml of dilute hydrochloric acid solution, add 1.0 ml of barium chloride solution (100 g / ml). L) and shaking for 1/2 minute.

Within 15 minutes of shaking, the non-wetted solution becomes more cloudy than the reference sample. 20. Sulphides, acid sulphides - testing of ČSN 62 1156 - Chemical testing of rubber harmless in water extract as follows:

Claims (3)

SUBJECT Method for the determination of the safety of rubber plugs in health, characterized in that in a glucose solution with a concentration of 5% to 40% w / v. after contacting the stopper with this solution for 30 minutes at a temperature of 120 ° C and a pressure of 0.101 325 MPa it determines the appearance of the solution, the appearance of the stopper, actual acidity, conductivity, foreign organic contamination spectrophotometrically in the wavelength range 220 to 360 nm glucose, an arsenic, barium, borate, aluminum, magnesium, heavy metals two-way test, titanium, calcium, strontium, zinc, iron, chlorides, phosphates, sulfates, sulfides, acid sulfides, thiosulfates and quantitative glucose determination are performed.