Method for detecting dissolution rate of preparation containing colloidal bismuth pectin

Abstract

A method for detecting a dissolution rate of a preparation containing colloidal bismuth pectin includes steps of: according to Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, dispersing the preparation containing the colloidal bismuth pectin into dissolution medium, and directly obtaining dissolution liquid; adding a protonic acid dissociation agent into the dissolution liquid until a hydrogen ion concentration reaches 0.8-1.2 mol/L; centrifuging for separating a supernatant; coloring the supernatant by adding a chromogen solution of citric acid or ascorbic acid and potassium iodide to obtain a test solution; calculating a dissolution amount, which is accounted by bismuth, of the colloidal bismuth pectin with a spectrophotometry method. The method of the present invention well detects dissolution curves and rates of the colloidal bismuth pectin in the preparation thereof, satisfying quality control requirements.

Claims

1. A method for detecting a dissolution rate of a preparation containing colloidal bismuth pectin, comprising steps of: according to Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, dispersing the preparation containing the colloidal bismuth pectin into dissolution medium, dissolving for 3-120 min with a centrifuging rate of 30-150 r/min, and directly obtaining dissolution liquid; adding a protonic acid dissociation agent into the dissolution liquid until a hydrogen ion concentration reaches 0.8-1.2 mol/L; centrifuging after completely dissociation; separating a supernatant; coloring the supernatant by adding a chromogen solution of citric acid or ascorbic acid and potassium iodide to obtain a test solution; testing an absorbance of the test solution at a wavelength of 380-470 nm; comparing the absorbance of the test solution with an absorbance of a reference solution with a known bismuth concentration under same conditions; calculating a dissolution amount, which is accounted by bismuth, of the colloidal bismuth pectin; wherein the dissolution medium is water, a buffer solution with a pH of 1.0-10.0, or an acid solution.

2. The method, as recited in claim 1, wherein the preparation containing the colloidal bismuth pectin is a single preparation or a compound preparation, which comprises tablets, dispersible tablets, enteric-coated tablets, colon-enteric-coated tablets, capsules, soft capsules, enteric-coated capsules, colon-enteric-coated capsules, granules, dripping pills, microcapsules and dry suspension.

3. The method, as recited in claim 1, wherein the buffer solution is an acetate buffer solution, a phthalate buffer solution, a phosphate buffer solution or a borate buffer solution, with a pH of 1.0-10.0.

4. The method, as recited in claim 1, wherein the acid solution is a 0.005-0.1 mol/L hydrochloric acid solution.

5. The method, as recited in claim 1, wherein the dissolution detection method is a basket apparatus, a paddle apparatus or a cup apparatus in the Pharmacopoeia of the People's Republic of China, Volume 2, Appendix XC.

6. The method, as recited in claim 1, wherein the protonic acid dissociation agent is nitric acid, hydrochloric acid or sulfuric acid.

7. The method, as recited in claim 1, wherein the chromogen solution is a water solution or a 0.2-2 mol/L nitric acid solution of the potassium iodide, with the citric acid or the ascorbic acid.

8. The method, as recited in claim 7, wherein the chromogen solution comprises the citric acid or the ascorbic acid of 0.5 wt %-10 wt %, and the potassium iodide of 2.5 wt %-25 wt %.

9. The method, as recited in claim 1, wherein the reference solution of the bismuth is prepared by dissolving metal bismuth in nitric acid before being diluted with water and adding the chromogen solution.

10. The method, as recited in claim 1, wherein a bismuth content per 1 ml of the test solution or 1 ml of the reference solution of the bismuth is 0.1-50 g.

11. The method, as recited in claim 1, wherein the dissolution liquid dissociated with the protonic acid is centrifuged for 5-15 min with a centrifuging rate of 7000-10000 r/min.

12. The method, as recited in claim 1, wherein a single-wavelength method is adopted for measurement with any wavelength of 399 nm, 433 nm and 463 nm; or a double-wavelength method is adopted for measurement with any two wavelengths of 399 nm, 433 nm and 463 nm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] FIG. 1 is dissolution rate curves of colloidal bismuth pectin capsules in water.

[0028] FIG. 1 is dissolution rate curves of colloidal bismuth pectin tablets in a phosphate buffer solution.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0029] Embodiment 1: colloidal bismuth pectin dispersible tablet (50 mg accounted by bismuth)

[0030] 1) Preparation of a chromogen solution: placing 5 g ascorbic acid and 25 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25ml of a nitric acid solution of 1 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 2.5% of the ascorbic acid and 12.5% of potassium iodide.

[0031] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; accurately weighing 2 ml of the standard bismuth stock solution to place in a 100 ml volumetric flask; diluting with a 1 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 55 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0032] 3) Preparation of a test solution: taking the colloidal bismuth pectin dispersible tablet; according to a second method (paddle apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 900 ml water as dissolution medium, dissolving for 20 min with a rate of 100 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2 mol/L nitric acid solution; shaking for 10 minutes; centrifuging for 10 min at 8000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0033] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0034] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 463 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin dispersible tablet for calculating a dissolution rate.

[0035] According to results, the dissolution rates of six colloidal bismuth pectin dispersible tablets are respectively 96.2%, 92.5%, 94.3%, 95.6%, 91.5%, and 93.3%; an average value is 94%.

[0036] Embodiment 2: colloidal bismuth pectin enteric-coated tablet (100 mg accounted by bismuth)

[0037] 1) Preparation of a chromogen solution: placing 15 g citric acid and 50 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 2 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 7.5% of the citric acid and 25% of potassium iodide.

[0038] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 2 ml of the standard bismuth stock solution to place in a 50 ml volumetric flask; diluting with a 1.2 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 110 m bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0039] 3) Preparation of a test solution: taking the colloidal bismuth pectin enteric-coated tablet; according to a first method (basket apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010Edition, Volume 2, Appendix XC, using 900 ml phosphate buffer solution with a pH of 6.8 as dissolution medium, dissolving for 60 min with a rate of 50 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 2.4 mol/L nitric acid solution; shaking for 5 minutes; centrifuging for 15 min at 7000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0040] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2.4 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0041] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 399 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin enteric-coated tablet for calculating a dissolution rate.

[0042] According to results, the dissolution rates of six colloidal bismuth pectin enteric-coated tablets are respectively 94.2%, 93.2%, 96.3%, 94.8%, 96.5%, and 96.1%; an average value is 95%.

[0043] Embodiment 3: colloidal bismuth pectin capsule (50 mg accounted by bismuth) 1) Preparation of a chromogen solution: placing 1 g citric acid and 5 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 10 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 0.5% of the citric acid and 2.5% of potassium iodide.

[0044] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 1 ml of the standard bismuth stock solution to place in a 100 ml volumetric flask; diluting with a 1.1 mol/L hydrochloric acid solution until a scale is reached, so as to obtain a solution containing about 27.5 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 1 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0045] 3) Preparation of a test solution: taking the colloidal bismuth pectin capsule;

[0046] according to a first method (basket apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 1000 ml acetate buffer solution with a pH of 4.0 as dissolution medium, dissolving for 45 min with a rate of 75 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 2.2 mol/L hydrochloric acid solution; shaking for 5 minutes; centrifuging for 5 min at 10000 r/min; accurately measuring 1 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0047] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2.2 mol/L hydrochloric acid solution; shaking for 5 minutes; accurately measuring 1 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0048] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 399 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin capsule for calculating a dissolution rate.

[0049] According to results, the dissolution rates of six colloidal bismuth pectin capsules are respectively 96.5%, 98.7%, 95.4%, 97.3%, 96.1%, and 94.7%; an average value is 96%.

[0050] Embodiment 4: colloidal bismuth pectin colon-enteric-coated capsule (50 mg accounted by bismuth)

[0051] 1) Preparation of a chromogen solution: placing 20 g ascorbic acid and 20 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 50 ml of a nitric acid solution of 2 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 10% of the ascorbic acid and 10% of potassium iodide.

[0052] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 1 ml of the standard bismuth stock solution to place in a 25 ml volumetric flask; diluting with a 0.6 mol/L sulfuric acid solution until a scale is reached, so as to obtain a solution containing about 110 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 10 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0053] 3) Preparation of a test solution: taking the colloidal bismuth pectin colon-enteric-coated capsule; according to a third method (cup apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2,Appendix XC, using 200 ml sodium borate buffer solution with a pH of 8.5 as dissolution medium, dissolving for 90 min with a rate of 30r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 1.2 mol/L sulfuric acid solution; shaking for 5 minutes; centrifuging for 15 min at 8000 r/min; accurately measuring 10 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0054] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 1.2 mol/L sulfuric acid solution; shaking for 5 minutes; accurately measuring 10 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0055] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 433 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin colon-enteric-coated capsule for calculating a dissolution rate.

[0056] According to results, the dissolution rates of six colloidal bismuth pectin colon-enteric-coated capsules are respectively 98.2%, 97.3%, 96.9%, 99.6%, 97.8%, and 99.2%; an average value is 98%.

[0057] Embodiment 5: colloidal bismuth pectin powder (50 mg accounted by bismuth)

[0058] 1) Preparation of a chromogen solution: placing 10 g ascorbic acid and 30 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 5 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 5% of the ascorbic acid and 15% of potassium iodide.

[0059] 2) Preparation of a reference solution of bismuth: placing 250 mg accurately weighed bismuth in a 50 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 1 ml of the standard bismuth stock solution to place in a 50 ml volumetric flask; diluting with a 1.1 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 100 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0060] 3) Preparation of a test solution: taking the colloidal bismuth pectin powder; according to a second method (paddle apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 500 ml phthalate buffer solution with a pH of 5.8 as dissolution medium, dissolving for 120 min with a rate of 30 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 2.2 mol/L nitric acid solution; shaking for 5 minutes; centrifuging for 10 min at 10000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0061] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2.2 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0062] 5) Measuring: taking the reference solution and the test solution of the bismuth;

[0063] adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at wavelengths of 433 nm and 463 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method according to an absorbance difference at the two wavelengths; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin powder for calculating a dissolution rate.

[0064] According to results, the dissolution rates of six pockets of the colloidal bismuth pectin powder are respectively 95.1%, 99.3%, 97.9%, 96.2%, 95.6%, and 98.3%; an average value is 97%.

[0065] Embodiment 6: colloidal bismuth pectin granule (150 mg accounted by bismuth)

[0066] 1) Preparation of a chromogen solution: placing 5 g ascorbic acid and 40 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 2 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 2.5% of the ascorbic acid and 20% of potassium iodide.

[0067] 2) Preparation of a reference solution of bismuth: placing 500 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 1 ml of the standard bismuth stock solution to place in a 50 ml volumetric flask; diluting with a 0.9 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 100 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 2 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0068] 3) Preparation of a test solution: taking the colloidal bismuth pectin granule; according to a second method (paddle apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 750 ml 0.01 mol/L hydrochloric solution as dissolution medium, dissolving for 30 min with a rate of 50 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 1.8 mol/L nitric acid solution; shaking for 5 minutes; centrifuging for 10 min at 7000 r/min; accurately measuring 2 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0069] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 1.8 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 2 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0070] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at wavelengths of 399 nm and 463 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method according to an absorbance difference at the two wavelengths; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin granule for calculating a dissolution rate.

[0071] According to results, the dissolution rates of six colloidal bismuth pectin granules are respectively 93.2%, 94.0%, 92.9%, 96.7%, 94.7%, and 90.6%; an average value is 94%.

[0072] Embodiment 7: colloidal bismuth pectin dry suspension (150 mg accounted by bismuth)

[0073] 1) Preparation of a chromogen solution: placing 8 g ascorbic acid and 50 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 4% of the ascorbic acid and 25% of potassium iodide.

[0074] 2) Preparation of a reference solution of bismuth: placing 250 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 5 ml of the standard bismuth stock solution to place in a 25 ml volumetric flask; diluting with a 0.8 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 500 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 2 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0075] 3) Preparation of a test solution: taking the colloidal bismuth pectin dry suspension; according to a third method (cup apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 150 ml 0.1 mol/L hydrochloric acid solution as dissolution medium, dissolving for 60 min with a rate of 45 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 1.6 mol/L nitric acid solution; shaking for 5 minutes; centrifuging for 15 min at 7000 r/min; accurately measuring 2 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0076] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 1.6 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 2 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0077] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 433 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin dry suspension for calculating a dissolution rate.

[0078] According to results, the dissolution rates of six pockets of colloidal bismuth pectin dry suspension are respectively 95.2%, 93.3%, 91.6%, 92.9%, 93.0%, and 90.1%; an average value is 93%.

[0079] Embodiment 8: compound colloidal bismuth pectin capsule (comprising colloidal bismuth pectin, metronidazole and tetracycline hydrochloride, wherein 35 mg accounted by bismuth for each capsule)

[0080] 1) Preparation of a chromogen solution: placing 15 g citric acid and 30 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of 1 mol/L nitric acid solution; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 7.5% of the citric acid and 15% of potassium iodide.

[0081] 2) Preparation of a reference solution of bismuth: placing 250 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 3 ml of the standard bismuth stock solution to place in a 100 ml volumetric flask; diluting with a 1.2 mol/L hydrochloric acid solution until a scale is reached, so as to obtain a solution containing about 75 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0082] 3) Preparation of a test solution: taking the compound colloidal bismuth pectin capsule; according to a third method (cup apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 250 ml 0.01 mol/L hydrochloric acid solution as dissolution medium, dissolving for 5 min with a rate of 150 r/min, and obtaining dissolution liquid; accurately weighing 5 ml to place in a centrifugal tube; accurately adding 5 ml of 2.4 mol/L hydrochloric acid solution; shaking for 10 minutes; centrifuging for 12 min at 7000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0083] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2.4 mol/L hydrochloric acid solution; shaking for 10 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0084] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 399 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the compound colloidal bismuth pectin capsule for calculating a dissolution rate.

[0085] According to results, the dissolution rates of six compound colloidal bismuth pectin capsules are respectively 92.3%, 91.6%, 90.9%, 92.1%, 89.6%, and 94.1%; an average value is 92%.

[0086] Embodiment 9: detection of dissolution curve of colloidal bismuth pectin capsule (100 mg accounted by bismuth)

[0087] 1) Preparation of a chromogen solution: placing 5 g ascorbic acid and 25 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 1 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 2.5% of the ascorbic acid and 12.5% of potassium iodide.

[0088] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 2 ml of the standard bismuth stock solution to place in a 100 ml volumetric flask; diluting with a 1 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 55 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0089] 3) Preparation of a test solution: taking the colloidal bismuth pectin capsule;

[0090] according to a second method (paddle apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 900 ml water as dissolution medium, dissolving for 60 min with a rate of 75 r/min, and obtaining 10 ml dissolution liquid respectively at 10 min, 20 min, 30 min, 45 min and 60 min; accurately weighing 5 ml the dissolution liquid to place in a centrifugal tube; accurately adding 5 ml of 2 mol/L nitric acid solution; shaking and then centrifuging for 10 min at 8000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0091] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2 mol/L nitric acid solution; shaking for 10 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0092] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 463 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin capsule for calculating dissolution rates at different time points for drawing the dissolution curve.

[0093] According to results, average dissolution rates of six colloidal bismuth pectin capsules at 10 min, 20 min, 30 min, 45 min and 60 min are respectively 7.8%, 28.5%, 70.3%, 87.4%, and 101.3%; the dissolution curve is shown as FIG. 1.

[0094] Embodiment 10: detection of dissolution curve of colloidal bismuth pectin tablet (50 mg accounted by bismuth)

[0095] 1) Preparation of a chromogen solution: placing 10 g citric acid and 25 g potassium iodide in a 200 ml volumetric flask; adding 100 ml of water; shaking to dissolve; adding 25 ml of a nitric acid solution of 4 mol/L; adding water to dilute; dripping water to meet a scale, so as to obtain the chromogen solution containing 5% of the citric acid and 12.5% of potassium iodide.

[0096] 2) Preparation of a reference solution of bismuth: placing 275 mg accurately weighed bismuth in a 100 ml volumetric flask; adding 6.4 ml nitric acid to dissolve the bismuth; diluting with water until a scale is reached, so as to obtain a standard bismuth stock solution; weighing 1 ml of the standard bismuth stock solution to place in a 100 ml volumetric flask; diluting with a 1.2 mol/L nitric acid solution until a scale is reached, so as to obtain a solution containing about 27.5 g bismuth per 1 ml as a standard bismuth solution; accurately weighing 5 ml of the standard bismuth solution to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the reference solution of the bismuth.

[0097] 3) Preparation of a test solution: taking the colloidal bismuth pectin tablet; according to a first method (basket apparatus) of dissolution detection in Pharmacopoeia of the People's Republic of China, 2010 Edition, Volume 2, Appendix XC, using 900 ml phosphate buffer solution with a pH of 6.8 as dissolution medium, dissolving for 60 min with a rate of 100 r/min, and obtaining 10 ml dissolution liquid respectively at 10 min, 20 min, 30 min, 45 min and 60 min; accurately weighing 5 ml the dissolution liquid to place in a centrifugal tube; accurately adding 5 ml of 2.4 mol/L nitric acid solution; shaking and then centrifuging for 5 min at 10000 r/min; accurately measuring 5 ml of supernatant to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the test solution.

[0098] 4) Preparation of a blank solution: accurately measuring 5 ml water to place in a 15 ml centrifugal tube; accurately adding 5 ml of 2.4 mol/L nitric acid solution; shaking for 5 minutes; accurately measuring 5 ml to place in a 25 ml volumetric flask; diluting with the chromogen solution until a scale is reached, so as to obtain the blank solution.

[0099] 5) Measuring: taking the reference solution and the test solution of the bismuth; adopting the blank solution as a reference; applying ultraviolet-visible spectrophotometry, using a 1 cm quartz cuvette, measuring an absorbance at a wavelength of 463 nm, and calculating the colloidal bismuth pectin content accounted by the bismuth with an external standard method; comparing with a colloidal bismuth pectin nominal value of the colloidal bismuth pectin tablet for calculating dissolution rates at different time points for drawing the dissolution curve.

[0100] According to results, average dissolution rates of six colloidal bismuth pectin capsules at 10 min, 20 min, 30 min, 45 min and 60 min are respectively 12.3%, 48.9%, 86.2%, 103.6%, 101.7%; the dissolution curve is shown as FIG. 2.