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Test Method For Empty Gelatin Capsules

  Empty gelatin capsules are made of gelatin and are used in capsules with excipients.

  Describes the cylindrical, rigid, elastic empty pharmaceutical capsule, consisting of a retractable cap and body. The surface of the capsule should be clean, smooth, uniform in color, odorless, trimmed neatly, and not deformed when formed. It can be clear (both without sunscreen), translucent (both with sunscreen), or opaque (both with sunscreen).

  Identification (1) Dissolve 0.25 g in 50 ml of water, heat, cool, and shake well. Add a few drops of a mixture of potassium dichromate TS and dilute hydrochloric acid (4:1) to 5 ml of the solution to form a flocculent precipitate.

  (2) Take 1 ml of the identification solution obtained in test (1), add 50 ml of water, and add a few drops of tannic acid TS after mixing. produces opalescence.

  (3) Take 0.3g into a test tube, add an appropriate amount of soda lime, and heat. The resulting gas turns the moist red light blue.

  Dense Take 10 capsules, gently press the cap and the end of the bottle with your thumb and forefinger and twist to open without sticking, deformation or breakage. Fill the bottle with talc, engage and lock the capsules, and drop each filled capsule from a height of 1 meter to a 2 cm thick wooden board. No powder leakage or slight leakage of no more than 1 capsule. If more than 1 capsule fails, the test is repeated and another 10 meet the requirements.

  Friability Place 50 capsules in a petri dish in a desiccator with saturated magnesium nitrate solution and let stand at 25°C ± 1°C for 24 hours. Remove and immediately place individual capsules in glass tubes (24 mm inner diameter and 200 mm long) vertically on a wooden board (20 mm thick). Freely drop a cylindrical counterweight (made of Teflon, 22 mm in diameter, weighing 20 ± 1 g) onto the capsule from the top of the glass tube. No more than 5 capsules are broken.

  Disintegration 6 capsules filled with talc and tested for disintegration

  (Appendix XA). All 6 capsules should disintegrate within 10 minutes. If 1 capsule fails, repeat the test with another 6 capsules. All capsules should meet the test.

  Sulfites (as SO 2 ) Put​​ 5.0 g in a long neck round bottom flask, soak in 100 ml hot water, and allow to swell. Add 2 ml phosphoric acid and 0.5 g sodium bicarbonate and immediately connect the flask to the condenser. Distill under the surface of 15 ml of 0.05 mol/L iodine solution and collect 50 ml of distillate. Dilute the solution to 100 ml with water. Stir well, take a 50ml water bath to evaporate, add a certain volume of water in time, and continue to evaporate until the liquid is almost colorless. Dilute the solution to 40 ml with water and carry out the sulfate limit test (Appendix B). Any opalescence produced was no more pronounced than the reference solution using a 3.75 ml potassium sulfate standard solution (0.01%).

  Parabens Place an accurately weighed 0.5 g capsule into a separatory funnel with 30 ml of hot water, shake to dissolve, and cool. Add exactly 50 ml of ether and shake carefully to separate. A. Accurately transfer 25ml of the ether layer to an evaporating dish, evaporate the ether, transfer it to a 5ml volumetric flask with the mobile phase, dilute it to the mark with the mobile phase, and mix well to obtain the solution to be tested. Accurately weigh 25 mg of methyl parahydroxybenzoate CRS, ethyl parahydroxybenzoate CRS, propyl parahydroxybenzoate, and butyl parahydroxybenzoate CRS, and place them together in a 250ml volumetric flask. Dilute to volume and shake. Accurately transfer 5 ml of the solution to a 25 ml volumetric flask, dilute to volume with mobile phase, and mix to serve as a reference solution. Perform high-performance liquid chromatography (Appendix VD) using packed octadecylsilane-bonded silica gel and methanol and 0.02 mol/L ammonium acetate (58:42) as mobile phase. The detection wavelength is 254 nm, and the theoretical plate number should not be less than 1600 calculated from the peak of ethyl p-hydroxybenzoate. Accurately inject 10 μl of the test solution and the reference solution into the column respectively, and record the chromatogram. The content of methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, and butyl p-hydroxybenzoate relative to the peak area was calculated by the external standard method. 05%。 The total amount of methylparaben, ethylparaben, propylparaben, butylparaben does not exceed 0.05%. (These project tests products with added paraben antibacterial agents).

  Vinyl chloride (this product is sterilized by the oxetane method). Cut the capsules into pieces, accurately weigh 2.5 grams, put them in a stoppered conical flask, add 25 ml of n-hexane, and soak them overnight. Transfer to a separator, add exactly 2 ml of water, shake and allow to separate. Take the water layer as the test solution. Accurately weigh a certain amount of vinyl chloride, dissolve it in n-hexane and dilute it with n-hexane to make a solution containing 22 micrograms per milliliter, and accurately transfer 2 ml of vinyl chloride solution to a separator containing 24 ml of n-hexane. -Hexane, accurately add 2ml of water for extraction and take the water layer as the reference solution. Perform gas chromatography (Appendix VE) using a capillary column packed with 10% polyethylene glycol maintained at 110°C. Any peak area caused by vinyl chloride in the chromatogram obtained with the test solution is not greater than the main peak (0.0002%) obtained with the reference solution.

  Oxane (this item is a test for sterilized products by the oxane method). Weigh 2.0g capsules and place them in a 20ml headspace bottle, add 10ml of 60°C water accurately, and seal and shake well to dissolve as a test solution. Place approximately 60 ml of water in a 100 ml volumetric flask, dry and stopper, and weigh accurately. Inject 0.3 ml of oxane, shake without a stopper, stopper and weigh accurately. The difference in weight is the weight of oxane in the solution. Take an appropriate amount of the solution and dilute it with water to make a solution containing 2 μg per milliliter as a reference solution. Transfer exactly 1 ml of the reference solution to a 20 ml headspace vial and add exactly 9 ml of water. Carry out a residual solvent test (Appendix VIIP Method 2). Use a column packed with 5% methylpolysiloxane or polyethylene glycol (or a stationary phase of similar polarity). Keep the column temperature at 45°C and equilibrate the headspace vial at 80°C for 15 minutes. The peak area due to oxane in the chromatogram of the test solution should not be greater than the main peak area (0.0001%) of the reference solution.

  Weight loss on drying Accurately weigh 1.0 g, separate the body from the cap, and dry at 105°C for 6 hours, with a weight loss of 12.5% ​​to 17.5%.

  Ignition residues not exceeding 2.0% (transparent), 3.0% (translucent), 5.0% (opaque) (Appendix VIII N), use 1.0 g.

  Accurately weigh 0.5 g of chromium into a PTFE container, add 5-10 ml of nitric acid, shake well, and pre-sterilize at 100 °C for 2 hours. Stopper and allow digestion in a microwave digestion system. When digestion is complete, evaporate the solution on a hot plate until no more reddish-brown fumes are produced and near dryness, and heat gently. Transfer to a 50 ml volumetric flask, add 2% nitric acid, dilute to the mark, and use as the test solution (if the capsule contains titanium dioxide, centrifuge or filter the disintegrated test solution, and take the supernatant or updated filtrate as the Test solution, or add 1 ml of hydrofluoric acid for disintegration before disintegration.). Carry out a blank test and omit the checked substance. The resulting solution was used as a blank solution. Accurately transfer the appropriate amount of chromium standard solution and dilute with 2% nitric acid solution to

  Generate a 1.0 μg/ml solution as a chromium standard stock solution. Before the measurement, accurately pipette an appropriate amount of chromium standard stock solution, and dilute it with 2% nitric acid solution into a continuous solution of 0-80 ng per milliliter, as the chromium standard solution. Perform atomic absorbance spectrophotometry (Appendix XII D, Method 1) to determine the absorbance at 357.9 nm of the reference and test solutions. Calculated chromium content does not exceed 0.0002%. For arbitration, using inductively coupled plasma mass spectrometry (Appendix XII D, Method 1).

  Heavy metals are subjected to the heavy metal limit test, add 0.5ml of nitric acid, evaporate to remove nitrogen oxide vapor, cool, add 2ml of hydrochloric acid, evaporate in a water bath, add 5ml of water, dissolve slightly and heat, filter (transparent hollow capsule does not need to be filtered), and the residue is washed with 15ml of water, Combine the filtrate and washings into tube B. Check according to (Appendix VIIIH Method 2). If the presence of iron oxide pigments in the hollow capsules would interfere with the results, follow the first method after the procedure "...transfer to a nano pigment cuvette and dilute to 25 ml with water". Use the residue obtained in the test for burning residues not exceeding 0.004%.

  The microbial limit is tested for the microbial limit (Appendix XI J), the number of bacteria does not exceed 1000 CFU, the number of fungi and yeast does not exceed 100 CFU, each gram of the tested substance does not contain Escherichia coli, and the Salmonella does not exist per 10 grams of the tested substance.

  Category Pharmaceutical pharmaceutical excipients used in the preparation of empty pharmaceutical capsule.

  Storage Keep in an airtight container at a temperature of 10-25°C and

  Relative humidity 35%-65%.

  Mark 1 should indicate the name of the corrosion inhibitor used and whether ethylene oxide is used for sterilization; 2 should indicate the marked value and range of the product's kinematic viscosity (which can be determined by the following methods).

  Viscosity Put 4.50 g in a pre-weighed 100 ml beaker, add 20 ml warm water, and heat in a 60°C water bath with gentle stirring to dissolve. Remove the beaker from the tub and quickly wipe the water off the outside. Add water to the gel solution to the total weight (15.0% dry matter) required by the following formula. Place the homogenized solution in a dry, stoppered Erlenmeyer flask, cap tightly, and place in a water bath at 40 °C ± 1 °C. When the gel solution reaches 40°C ± 1°C, transfer the solution to an Ostwald-type viscometer and carry out a viscometry test in a water bath at 40°C ± 0.1°C (Appendix VI G, Method 1, using an inner diameter of 2.0 mm). capillary).