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 enteric gelatin capsules.This standard is applicable to empty hard capsules made of gelatin and auxiliary materials and suitable enteric coating materials, divided into enteric-coated capsules and colonic enteric-coated capsules, gelatin and enteric materials should meet medicinal requirements.
Specifications: empty enteric gelatin capsule (hereinafter referred to as "capsule") is a cylindrical hard capsule with a cap and body sections that are enteric coated, and various locking structure. Capsules are divided into 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).
Physical and chemical indicators of capsules
|Identification||-||Conforms to composition|
|Disintegration time||In hydrochloric acid solution (9→1000), no disintegration in 120min||min||120|
|Enteric empty capsule||Completely disintegrated in 60min in artificial intestinal juice||min||60|
|Colonic enteric empty capsule||in phosphate buffer (pH 6.8), does not disintegrate within 180 min||min||180|
|in phosphate buffer solution (pH 7.8), completely disintegrated within 60min||min||60|
|Sulfite (in SO2)||mg/kg||≤ 100|
|Loss on drying||%||11.0~16.0|
|Ignition residue||transparent||%||≤ 2.0|
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|
potassium dichromate test solution, dilute hydrochloric acid, tannin test solution, sodium lime, and a litmus test paper.
Take 0.25g of the product, separate the capsules and put the capsule caps and bodies into a beaker. Add 50ml of water, heat the dissolute capsules, and then cool it down. Take 5 ml of solution, add a few drops of potassium chromate test solution - dilute hydrochloric acid (4:1), and then orange-yellow flocculent precipitate is produced. Take 1 ml of the 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.
Reagents, instruments and excipients
a disintegration time tester (temperature is controlled at 37 ± 1 ° C), talcum powder (hydrochloric acid, pepsin, potassium dihydrogen phosphate, sodium hydroxide, trypsin, disodium hydrogen phosphate, sodium dihydrogen phosphate), hydrochloric acid solution (slowly add 9 ml of hydrochloric acid to the purified water, with stirring, and make the temperature of the solution cool down to room temperature, and the final volume of the solution is 1000 ml, shake well.), artificial intestinal juice (take 2.8 g of potassium dihydrogen phosphate, add 500 ml of water to dissolve, use 0.1 mol / L sodium hydroxide solution to adjust the pH to be 6.8. Take another 10g of trypsin, add water to dissolve, and then mix two cup of solution and dilute to 1000ml with water), phosphate buffer A (Take 250ml of 0.2mol/L potassium dihydrogen phosphate solution, add 118ml of 0.2mol/L sodium hydroxide solution, dilute to 1000ml with water, shake well), phosphate buffer B (solution A: take 35.9g of disodium hydrogen phosphate, add water to dissolve and dilute to 500ml, solution B: take 2.76g of sodium dihydrogen phosphate, add water to dissolve and dilute to 100ml. Take 91.5ml of the above solution A and 8.5ml of solution B, mix them and shake well.)
take 6 enteric capsules, fill them with talcum powder (the filled capsule shall not float on the water), lock the capsules, and place capsules in the glass tube of the hanging basket separately, and then put them in thehydrochloric acid solution without baffle. There should be no capsule cracks or disintegration in 120 min. Take out the hanging baskets, and wash them with some water and put on the baffle on each tube. Then test the capsules in artificial intestinal juice, and all capsules should be disintegrated in 60 min. If one of the capsules does not disintegrate, should test another 6 capsules, and all of them should meet the requirements. Take 6 colonic enteric empty capsule, fill them with talcum powder (the filled capsule shall not float on the water), lock the capsules, and place capsules in the glass tube of the hanging basket separately, and then put them in thehydrochloric acid solution without baffle. There should be no capsule cracks or disintegration in 120 min. Take out the hanging baskets, and wash them with some water and test the capsules in the phosphate buffer A, and there should be no capsule cracks or disintegration in 180 min. After that, take out the hanging baskets, and wash them with some water and put on the baffle on each tube, and test them in phosphate buffer B, and all capsules should be disintegrated in 60 min. It is allowed if there are some capsule fragments. If one of the capsules does not disintegrate, should test another 6 capsules, and all of them should meet the requirements.
put enteric empty capsules and colonic enteric-coated empty capsules into sterile phosphate buffer of pH 6.8 (for enteric preparations) or sterile phosphate buffer of pH 7.6 (for colonic preparations), and put them in a water bath of 45 ° C, shake to make test solution of 1:10. Then check according to microbiological limit check for non-sterile products: microbiological counting and non-sterile product microbial limit check: control bacteria test
The test methods for tightness, brittleness, sulfite, loss on drying, ignition residue, Pb, chromium, inspection rules, criterion rule, and product packaging, labeling, transportation, storage requirements are the same as those for empty gelatin capsule standard.