This standard specifies the specifications, technical indicators and requirements, test methods, inspection rules, criterion rule and requirements of product packaging, labeling, transportation and storage of empty gelatin capsules. This standard is applicable to empty hard gelatin capsules made of gelatin and auxiliary materials. Gelatin for capsules should meet the Capsule gelatin quality standard.
The empty gelatin capsule is a cylindrical hard capsule with a cap and body section, and various locking structures. Capsules are divided into 000#, 00#, 0 #, 1 #, 2 #, 3 #, 4 #, 5 # and other special sizes according to their capacity. Conventional extended capsules are represented by el, such as 0# el. The shape size and appearance shall conform to the specifications and appearance quality standards of the empty capsule. The special size can be set by the manufacturer. According to the transparency, the capsule can be divided into three types: transparent (both sections do not contain opacifier), opaque (both sections contain opacifier), and translucent (only one section contains opacifier).
after checking the outer packaging, according to the following table, take a certain quantity of samples from the products of one batch, for inspection.
|Number of packages per batch||Number of package need to be sampled|
Take out the same amount of sample from each package separately, and mix them up, the total amount should not be less than 90 g.
During checking, if any technical indicator fails to meet the requirements, the receiving party shall test it with the manufacturer together, and make the decision according to the test result.
Physical and chemical indicators of capsules
|Identification||—||Conforms to composition|
|Disintegration time||min||≤ 10|
|Sulfite (in SO2)||mg/kg||≤ 100|
|Loss on drying||%||13.0～17.0|
|Ignition residue transparent||%||≤ 2.0|
|Ignition residue translucent||%||≤ 3.0|
|Ignition residue opaque||%||≤ 5.0|
|Heavy metal (in Pb)||mg/kg||≤ 40|
If ethylene oxide sterilization or the paraben antibacterial agents are used during production, shall add the detection and control of the corresponding project.
|Total Bacterial count||cfu/g||≤ 1000|
|Yeast and Moldscount||cfu/g||≤ 100|
The color is uniform and shiny, and there is no obvious color difference among the productions of the same batch.
potassium dichromate test solution, dilute hydrochloric acid, tannin test solution, sodium lime, and a litmus test paper.
Take 0.25g of the product, add 50ml of water, heat the solution to dissolution, and then cool it down, and shake well. Take 5 ml of solution, add a few drops of potassium chromate test solution - dilute hydrochloric acid (4:1), and then flocculent precipitate is produced. Take 1 ml of the remaining solution, add 50 ml of water, shake well, add a few drops of tannin acid test solution, and turbidity will occur immediately.
Take about 0.3g of the product, put it in a test tube, add a little sodium lime, heat it, and the generated gas can make the wet red litmus paper blue.
Instruments and excipients
a disintegration time tester (temperature is controlled at 37 ± 1 ° C), talcum powder.
take 6 capsules, fill them with talcum powder (the filled capsule shall not float on the water), lock the capsules, and then place capsules in the glass tube of the hanging basket, put on the baffle. Based on disintegration time checking method, all the capsules should be completed disintegrated in 10 minutes, and there should be no other things left on the sieve excepting for the broken capsule shell. It is okay that there are some capsule fragments left. If some of the disintegrated capsules cannot pass through the sieve, but they are softened or lightly float on the water, it is also in accordance with the regulations. If one of the capsules does not disintegrate, should test another 6 capsules, and all of them should meet the requirements.
a wooden board (thickness of 2 cm)
take 10 capsules, use the thumb and forefinger to gently pinch the ends of the capsule, rotate and separate the capsules. There should be no sticking, deformation or cracking, then fill capsules with the talcum powder, and lock the capsules. Drop the capsules from the height of 1 m to the wooden board one by one, and there should be no powder leaked. If there is a small amount of powder leakage, the powder should come from one capsule. If exceeding, take another 10 capsules to test, and they should meet the requirements.
Reagents and instruments
saturated magnesium nitrate solution, a desiccator, a glass tube (24 mm of inner diameter, 200 mm of length), PTFE cylindrical weights (diameter of 22 mm, weight of 20.0 ± 0.1 g), and a wood board (thickness of 2 cm).
take 50 capsules, put them in a watch glass, and then transfer it into a desiccator containing a saturated solution of magnesium nitrate. Place the desiccator under 25 ° C ± 1 ° C for 24 h, then taken out the capsules and immediately put them into a glass tube standing upright on a wooden board separately. The cylindrical weight will freely fall from the opening of the glass tube, and the number of broken capsules shall not exceed 2.
Sulfite (in SO2)
Reagents and instruments
a long-neck round bottom flask of 500 ml, phosphate (Analytical Reagent), sodium bicarbonate (Analytical Reagent), iodine solution of 0.05mol / L, standard potassium sulfate solution (weighed potassium sulfate 0.181 g, put it in a volumetric flask of 1000 ml, add water to dissolve the potassium sulfate, and shake well. Each 1 ml contains 0.1 mg of SO42-)
accurately weigh 5.0 g of capsules, put them in a long round bottom flask; add hot water of 100 ml to dissolve the capsule, add 2 ml of phosphoric acid, 0.5 g of sodium bicarbonate, and connect the condenser immediately. Heat and distill the solution. Then use 15 ml iodine solution of 0.05mol/L as the receiving liquid to collect 50 ml of distillate. Dilute the solution to 100ml with water, shake well. Take out 50ml, and evaporate it in a water bath. Add some water at any time until the solution is almost colorless. Dilute the solution to 40ml with water, and put it in a Nessler glasses of 50 ml, add 2 ml of dilute hydrochloric acid, shake well, then comes out the test solution. Take another 3.75 ml of standard potassium sulfate solution, pour in a Nessler glasses of 50 ml, add water to 40 ml, add 2 ml of hydrochloric acid, and shake well for control solution. Add 5 ml of 25% barium chloride solution to the test solution and the control solution, dilute to 50 ml with water, shake well, and leave them for 10 min. Place them on a black background. Check and compare the Nessler glasses from above. The test solution should not be more turbid than the control solution.
Loss on drying
an analytical balance (accuracy 0.1 mg), a desiccator, a drying oven (the temperature is controlled at 105 ± 2 ° C), and a weighing bottle.
weigh capsules of 1.0 g, with an accuracy of 0.1 mg, place them in a weighing bottle which has been dried to be with constant weight, separate capsules into caps and bodies, dry them in a drying oven under 105 ° C for 6 h, take capsules out and cover the weighing bottle, and then move them to the desiccator until the temperature of the capsules are cooled down to the room temperature, and weighed accurately.
y= (m1-m2) / (m1-m0) ×100%
In the formula
y — loss on drying, %
m1 — the total weight of the weighing bottle and the sample before drying, in grams (g)
m2 — the total weight of the weighing bottle and the sample after drying, in grams (g)
m0 — the weight of the weighing bottle, in grams (g)
The result of the calculation is expressed as one decimal place. The absolute difference between the two tests under repetitive conditions should be no more than 0.4%.
Residue on ignition
a high-temperature furnace ( temperature is controlled 500~600 °C), an analytical balance (accuracy of 0.1 mg), a porcelain crucible (50 ml), and a desiccator.
weigh capsules of 1.0 g, with an accuracy of 0.1 mg, place them in a crucible which has been burned to be with constant weight, slowly ignite the capsules until they are complete carbonized, then cool them down to room temperature. Add 0.5 ml~ 1 ml of sulfuric acid to make it moist, and heat it with low temperature to remove all the sulfuric acid vapor, and then make it completely ashed at 600 °C. Then move them to the desiccator until the temperature of the capsules are cooled down to the room temperature, and weighed accurately.
d= (m1-m2) / (m1-m0) ×100%
In the formula
d — ignition residue, %
m2 — the total weight of the crucible and the sample after burning, in grams (g)
m0 — crucible weight, in grams (g)
m1 — the total weight of the crucible and the sample before burning, in grams (g)
The result of the calculation is expressed as one decimal place. The absolute difference between the two tests under repetitive conditions should be no more than 0.2%.
Heavy metals (in Pb)
Reagents and instruments
hydrochloric acid (Analytical Reagent), nitric acid (Analytical Reagent), ammonia test solution (take 400 ml of concentrated ammonia solution and add water to make solution of 1000 ml), acetate buffer (dissolve 25.0 g of ammonium acetate dissolved in the water of 25 ml, add 38 ml hydrochloric acid of 7 mol/L, adjust the pH to 3.5 with 2 mol/L hydrochloric acid solution or 5 mol/L ammonia solution (potential method), and then dilute the solution with water to 100 ml), phenolphthalein indicator solution (dissolve phenolphthalein 1 g in the Ethanol of 100 ml), lead standard solution (weigh 0.160 g of lead nitrate, put it in a volumetric flask of 1000 ml, add nitric acid of 5 ml of and water of 50 ml, then dilute with water until the liquid level is as high as the mark, shake well, and then it comes out stock solution. Pre-precision 10 ml of stock solution, pour it in a volumetric flask of 100 ml, dilute with water as required, and shake well. Each 1 ml contains 0.01 mg of Pb), thioacetamide test solution (dissolve 4 g of thioacetamide in the water to make the solution of 100ml and store it in the refrigerator. Before using, take the mixture (1 mol/L sodium hydroxide solution 15 ml, water 5.0 ml and glycerol 20 ml) 5 ml, add the above thioacetamide solution 1.0 ml, and heat the mixture on the water bath for 20 seconds, cool down, and use it immediately), Nessler glasses 25 ml.
take the residue left in the test of ignition residue, add 0.5ml of nitric acid, evaporate until the nitrogen oxide vapor is removed completed. Make it cool down, add 2ml of hydrochloric acid, and put it on the water bath, evaporate to dryness, and then add 5ml of water for dissolution, filter it. (when test transparent capsule, filtering is not needed). Wash the filter residue is washed with 15 ml of water, and pour the filtrate and the washing liquid into a tube. Get control solution by the same operation, and check according to the heavy metal inspection method.
Take 0.5g of the product, and put it in the tetrafluoroethylene disintegration tank, add 5~10ml of nitric acid, mix well, and pre-dissolve for overnight. Cover the inner lid, tighten the outer cover, and place it in a suitable microwave digestion furnace for disintegration. After the disintegration is completed, place the inner disintegration tank on the electric heating plate to heat slowly until reddish brown steam is all removed. Transfer it to a 50ml Teflon bottle with 2% nitric acid, and dilute it with water until the liquid level reaches the scale, and then shake well, then it comes out the test solution. If there is opacifier contained in the product, add 0.5ml of hydrofluoric acid after adding nitric acid, or centrifuge the test solution and take the supernatant of the test solution, so as to eliminate any other influence during the test. Make a blank solution with the same method. Then, take the chrome element standard solution and dilute it with 2% nitric acid to make Chromium standard stock solution of which there is 1.0μg of chromium standard stock solution per 1ml of solution. When using, accurately measure for an appropriate amount, and refer solution containing 0~80 ng of chromium per 1 ml, with 2% nitric acid solution. was made into a reference solution containing 0 to 80 ng of chromium per 1 ml. Take test solution and reference solution according to atomic absorption spectrophotometry, using graphite furnace as an atomizer and test at a wavelength of 357.9 nm.
check according to microbiological limit check for non-sterile products: microbiological counting and non-sterile product microbial limit check: control bacteria test
The inner packaging of the product shall be made of packaging materials that meet the requirements of food grade or pharmaceutical grade packaging. The outer packaging shall be corrugated cartons or negotiated by the supplier and the buyer.
The product label should comply with the requirements of relevant national laws and regulations. And the label shall include at least: the manufacturer’s name, the product name, the batch number, the date of manufacture, the expiration date, the execution standard, the quantity of the package, and the transportation and storage conditions.
The product should be protected against pressure, sun, moisture, and heat during transportation. Do not ship it with toxic or spoiled items.
The product shall be sealed and stored in a clean, dry and ventilated warehouse. It should not be stored in the open air. The relative humidity for storage should be 35%-65% and temperature should be 10°C～25°C.