Quality Standard and Detection Method Of Carbomer Copolymer In Chinese Pharmacopoeia
Carbomer copolymer is a long-chain alkyl methacrylate polymer copolymer of acrylic acid bonded polyols with non benzene solvent as polymerization solvent. According to the dry product, the carboxylic acid group (- cooh) shall be 52.0% ~ 62.0%.
1 Properties:
Carbomer copolymer is white loose powder; it has characteristic slight odor.
2 Identification
(1) take carbomer copolymer about 5g, add water 500ml, stir, should form dispersion liquid and appear foam layer, at room temperature for 1 hours, the foam layer will not disappear.
(2) the infrared light absorption spectrum (general rule 0402) of carbomer copolymer shall have characteristic absorption at 1710cm-1 ± 5cm-1, 1454cm-1 ± 5cm-1, 1414cm-1 ± 5cm-1, 1245cm-1 ± 5cm-1, 1172cm-1 ± 5cm-1, 1115cm-1 ± 5cm-1 and 801cm-1 ± 5cm-1, of which 1710cm-1 has the strongest absorption.
3 Inspection
3.1 acidity
Take 0.1g of carbomer copolymer, add 10ml of water to evenly disperse the swelling, check according to law (general rule 0631), and the ph value should be 2.5 ~ 3.5.
3.2 Viscosity
Take 5.0g of carbomer copolymer which has been dried under reduced pressure at 80 ℃ for 1 hour in advance, add 500ml of water while stirring to disperse evenly, adjust the ph value to 7.3 ~ 7.8 with 15% sodium hydroxide solution, mix evenly (avoid bubbles), and stand in a 25 ℃ water bath for 1 hour. The ph value shall not exceed 7.8. If the ph value is lower than 7.3, adjust it to 7.3 ~ 7.8 with sodium hydroxide solution. Select the appropriate rotor and rotating speed according to the following table and measure the dynamic viscosity according to law (general rule 0633 third method rotor type rotary viscometer). Type a shall be 4.5 ~ 13.5pa · s, type b shall be 10 ~ 29pa · s and type c shall be 25 ~ 45pa · s.
3.3 Residual solvents
Ethyl acetate and cyclohexane (determined when used in production process)
Take about 0.2g carbomer copolymer, accurately weigh it, place it in an empty bottle, accurately add 5ml dimethyl sulfoxide, seal it, and use it as the test solution; take an appropriate amount of ethyl acetate and cyclohexane respectively, accurately weigh, quantitatively dilute with dimethyl sulfoxide into a mixed solution containing 0.2mg of ethyl acetate and 0.12mg of cyclohexane per 1ml, accurately measure 5ml, place it in a top empty bottle, seal it and use it as the reference solution. According to the residual solvent determination method (general rule 0861 second method), use a capillary column with 100% dimethylpolysiloxane (or similar polarity) as the stationary liquid, program temperature rise, the initial temperature is 40 ℃, maintain for 3 minutes, raise the temperature to 120 ℃ at the rate of 5 ℃ per minute for 20 minutes, and then raise the temperature to 220 ℃ at the rate of 20 ℃ per minute for 3 minutes, then raise the temperature to 240 ℃ at the rate of 20 ℃ per minute for 8 minutes; injection port temperature: 260 ℃; detector temperature: 260 ℃; the balance temperature of headspace bottle is 85 ℃, and the balance time is 90 minutes. Take the control solution and the test solution for headspace injection respectively. The content of ethyl acetate shall not exceed 0.5% and cyclohexane shall not exceed 0.3% according to the peak area calculated by the external standard method.
3.4 Benzene
Take an appropriate amount of benzene, accurately weigh it, quantitatively dilute it with dimethyl sulfoxide to make a solution containing 1.0mg benzene per 1ml, accurately measure an appropriate amount, and quantitatively dilute it with water to make a solution containing 0.5 benzene per 1ml μ g as benzene stock solution. Take about 250mg of carbomer copolymer, accurately weigh it, place it in the top empty bottle, accurately add 10.0ml of 2% sodium chloride solution, mechanically mix evenly (about 30 minutes), seal it, and use it as the test solution. The solution should be injected within 3 hours after preparation; take about 250mg of carbomer copolymer, accurately weigh it, place it in the top empty bottle, accurately add 9.0ml of 2% sodium chloride solution, mechanically mix evenly (about 30 minutes), accurately add 1ml of benzene stock solution, mechanically mix evenly (about 1 minute), seal it, and use it as the reference solution. According to the residual solvent determination method (method 2 of general rule 0861), use a capillary column with 6% cyanopropyl phenyl-94% dimethylpolysiloxane as the stationary liquid, temperature programmed, the initial temperature is 40 ℃, maintained for 20 minutes, and the temperature is increased to 240 ℃ at the rate of 10 ℃ per minute for 20 minutes; the temperature of the sample inlet is 140 ℃, and the detector is a Hydro-gen flame ionization detector with a temperature of 250 ℃; the balance temperature of the headspace bottle is 80 ℃, the balance time is 60 minutes, and the headspace injection. With the reference solution as the system suitability solution, the chromatographic peak height of benzene shall be more than 10 times of the baseline noise. The sample shall be injected three times continuously, and the relative standard deviation of benzene peak area shall not exceed 15%. Take the control solution and the test solution for headspace injection respectively, and the peak area of benzene in the test solution shall not be greater than half (0.0002%) of the peak area of benzene in the control solution.
3.5 Acrylic Acid
Take carbomer copolymer about 0.1g, precision weighing, set up plug centrifuge tube, add water 9ml, shake 2 hours, add 50% sodium hydroxide solution 2 drops, shake, add 10% calcium chloride solution 1.0ml, shake to gel collapse, centrifugation, take supernatant filtrate, filtrate as test solution; take an appropriate amount of acrylic acid reference product, accurately weigh it, dissolve it with water and quantitatively dilute it to 25% per 1ml μ g as the control solution. As determined by high performance liquid chromatography (general rule 0512), octadecylsilane bonded silica gel was used as filler; take potassium diHydro-gen phosphate solution (take 1.36g of potassium diHydro-gen phosphate, add 1000ml of water to dissolve it, adjust the ph value to 3.0 ± 0.1 with phosphoric acid) - methanol (80:20) as the mobile phase; the detection wavelength is 200nm. Accurately measure 10% of the control solution and 10% of the test solution μ l. Inject into the liquid chromatograph and calculate the peak area according to the external standard method, which shall not exceed 0.25%.
3.6 Loss on Drying
Take carbomer copolymer and dry it under reduced pressure at 80 ℃ for 1 hour, and the weight loss shall not exceed 2.0% (general rule 0831).
3.7 Ignition Residue
Take 1.0g of carbomer copolymer, check according to law (general rule 0841), and the residue shall not exceed 2.0%.
3.8 Heavy Metals
Take the residue left under the item of ignition residue and check it according to law (method 2 of general rule 0821). The content of heavy metals shall not exceed 20 parts per million.
3.9 Content Determination
Take about 0.4g of carbomer copolymer that has been dried under reduced pressure at 80 ℃ for 1 hour, weigh it accurately, add 400ml of water, stir to dissolve it, add 2g of potassium chloride, titrate it with sodium hydroxide titrant (0.25mol/l) according to potentiometric titration (general rule 0701) (near the end point, stir it for at least 2 minutes after each drop). Every 1ml of sodium hydroxide titrant (0.25mol / l) is equivalent to 11.25mg - cooh.
4. Category
Pharmaceutical excipients, ointment matrix and release blockers, etc.
5. Storage
Sealed storage.
6. Marking
The viscosity type (type a, type b or type c), viscosity value, measuring instruments and parameters of carbomer copolymer shall be marked.
Note:
Carbomer copolymer is highly hygroscopic.
