Pharmaceutical composition containing potassium chloride and preparation method of preparation of pharmaceutical composition
By preparing a pharmaceutical composition containing potassium chloride, the problem of poor stability of existing potassium chloride oral preparations is solved, and a more stable potassium chloride oral solution is achieved, which is suitable for clinical applications.
Patent Information
- Application Number
- CN202411973136.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-30
- Publication Date
- 2025-03-18
AI Technical Summary
The current oral preparations of potassium chloride are poor in stability and are difficult to meet the stability requirements in clinical applications.
By preparing a pharmaceutical composition containing potassium chloride, the composition comprising potassium chloride, flavoring agent, bacteriostatic agent, pH adjusting agent, flavoring agent, coloring agent and solvent, the specific formulation is 10 parts by weight of potassium chloride, 2 parts by weight of glycerin, 0.072 parts by weight of sucralose, 0.05 parts by weight of sodium benzoate, 0.16 parts by weight of anhydrous citric acid, 0.24 parts by weight of sodium citrate, 0.04 parts by weight of orange essence, 6 parts by weight of sunset yellow and purified water, it is prepared into a liquid preparation or an oral solution.
The oral solution of this pharmaceutical composition has better stability and can maintain the stability of appearance traits, pH values and content under high temperature and light conditions, and is suitable for clinical applications.
Smart Images
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Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technology, and more particularly to a pharmaceutical composition containing potassium chloride and a preparation method thereof. Technical Background
[0002] Potassium chloride is an electrolyte supplement. Potassium is the main cation in cells and an important component for maintaining intracellular osmotic pressure. + , K + , and ATPase to maintain K inside and outside the cell + 、Na + The acid-base balance in the body affects potassium metabolism. For example, in acidosis, H + Entering the cell, in order to maintain the potential difference between the inside and outside of the cell, K + Released outside the cell, causing or aggravating hyperkalemia. The normal potassium ion concentration and concentration difference inside and outside the cell are closely related to certain functions of the cell. Potassium participates in the regulation of acid-base balance. The synthesis of sugar and protein and the conversion of adenosine diphosphate to triphosphate require a certain amount of potassium. Potassium participates in the excitation process between nerves and their innervated organs and neurons, and participates in the formation of nerve terminal transmitters (acetylcholine). The potassium content in the heart can affect its activity. When potassium is low, the excitability of the heart increases. Clinically, patients with low blood potassium mainly suffer from arrhythmia. Potassium is an ion necessary to maintain normal tension of skeletal muscle. Insufficient potassium ions manifest as muscle weakness and convulsions.
[0003] The main effects of oral potassium chloride preparations are: (1) Treatment of hypokalemia: hypokalemia caused by various reasons, such as insufficient food intake, vomiting, severe diarrhea, use of potassium-excreting diuretics, hypokalemic familial periodic paralysis, long-term use of glucocorticoids and supplementation of hypertonic glucose, etc. (2) Prevention of hypokalemia: When patients have potassium loss, especially if hypokalemia is harmful to the patient (such as patients using digitalis drugs), preventive potassium salt supplementation is required, such as eating very little, severe or chronic diarrhea, long-term use of adrenocorticoids, potassium-losing nephropathy, Bartter syndrome, etc. (3) Digitalis poisoning causes frequent, multifocal premature beats or rapid arrhythmias.
[0004] Potassium chloride oral solution is one of the dosage forms of potassium chloride oral preparations, which is suitable for patients with dysphagia and children. However, it is found in clinical applications that this type of product has poor stability. Therefore, it is of great significance to research and develop new potassium chloride oral solutions with better stability. Summary of the invention
[0005] Based on the above reasons, the applicant has obtained a new pharmaceutical composition containing potassium chloride as an active ingredient after several creative efforts, wherein the pharmaceutical composition comprises potassium chloride, flavoring agent, antibacterial agent, pH adjusting agent, flavoring agent, coloring agent, and solvent; more specifically, the pharmaceutical composition comprises 10 parts by weight of potassium chloride, 2 parts by weight of glycerol and 0.072 parts by weight of sucralose as flavoring agent, 0.05 parts by weight of sodium benzoate as antibacterial agent, 0.16 parts by weight of anhydrous citric acid and 0.24 parts by weight of sodium citrate as pH adjusting agent, 0.04 parts by weight of orange essence as flavoring agent, 6 parts by weight of sunset yellow as coloring agent, and purified water as solvent. The potassium chloride oral solution of the present invention has better stability.
[0006] The present invention is achieved through the following technical solutions.
[0007] A pharmaceutical composition containing potassium chloride comprises potassium chloride, a flavoring agent, an antibacterial agent, a pH regulator, a flavoring agent, a colorant and a solvent.
[0008] The pharmaceutical composition containing potassium chloride comprises potassium chloride, flavoring agents are glycerol and sucralose, antibacterial agent sodium benzoate, pH regulators are anhydrous citric acid and sodium citrate, flavoring agent is orange essence, coloring agent is sunset yellow, and solvent is purified water.
[0009] The pharmaceutical composition containing potassium chloride comprises 10 parts by weight of potassium chloride, 2 parts by weight of glycerol and 0.072 parts by weight of sucralose as flavoring agents, 0.05 parts by weight of sodium benzoate as an antibacterial agent, 0.16 parts by weight of anhydrous citric acid and 0.24 parts by weight of sodium citrate as pH adjusting agents, 0.04 parts by weight of orange essence as a flavoring agent, 6 parts by weight of sunset yellow as a coloring agent, and purified water as a solvent.
[0010] The pharmaceutical composition is prepared into a liquid preparation.
[0011] The pharmaceutical composition is prepared as an oral solution.
[0012] The preparation method of the oral solution is as follows:
[0013] Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, sodium benzoate to the above solution in turn, stir until dissolved and clear; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clear; then add purified water, stir to dissolve, filter, and fill. DETAILED DESCRIPTION
[0014] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention.
[0015] Test 1: Raw material stability and compatibility of raw and auxiliary materials
[0016] Table 1 Sample formula of raw material and auxiliary material compatibility test
[0017]
[0018]
[0019] Note: Component A contains 100g potassium chloride, 1.6g anhydrous citric acid and 2.4g sodium citrate.
[0020] Table 2 Preparation method of raw material and auxiliary material compatibility test samples
[0021]
[0022] Note: Preparation of buffer solution: Dissolve 16000mg of anhydrous citric acid and 24000mg of sodium citrate in pure water to 250ml for later use;
[0023] Table 3 Compatibility test results of raw materials and auxiliary materials
[0024]
[0025]
[0026] Compatibility test results of the original drug and excipients: (1) Full prescription solution: Under the conditions of high temperature of 60°C (30 days) and illumination of 4500lx (5 days, 10 days, and 12 days), the appearance, pH value, sodium benzoate, and content of the full prescription solution did not change significantly, and it was relatively stable. (2) Raw material + buffer solution and glycerol: Under the conditions of high temperature of 60°C (5 days, 10 days, and 30 days) and illumination of 4500lx (5 days, 10 days, and 12 days), the appearance, pH value, and content of the full prescription solution did not change significantly, and it was relatively stable. (3) Raw material + buffer solution and sodium benzoate: Under the conditions of high temperature of 60°C (5 days, 10 days, and 30 days) and illumination of 4500lx (5 days, 10 days, and 12 days), the appearance, pH value, sodium benzoate, and content did not change significantly, and it was relatively stable. (4) Raw materials + buffer solution and sucralose: Under the conditions of high temperature of 60°C (5 days, 10 days, 30 days) and illumination of 4500lx (5 days, 10 days, 12 days), the appearance, pH value and content did not change significantly, and were relatively stable. (5) Raw materials + buffer solution and flavor: Under the conditions of high temperature of 60°C (5 days, 10 days, 30 days) and illumination of 4500lx (5 days, 10 days, 12 days), the appearance, pH value and content did not change significantly, and were relatively stable. (6) Raw materials + buffer solution and sunset yellow: Raw materials and sodium benzoate under the conditions of high temperature of 60°C (5 days, 10 days, 30 days) and illumination of 4500lx (5 days, 10 days, 12 days), the appearance, pH value and content did not change significantly, and were relatively stable. (7) Raw materials + buffer solution: Under the conditions of high temperature of 60°C (5 days, 10 days, and 30 days) and illumination of 4500 lx (5 days, 10 days, and 12 days), the appearance, pH value, and content did not change significantly and were relatively stable.
[0027] The mixed samples of raw materials and single excipients under high temperature 60℃ (10 days, 30 days) and illumination 4500lx (10 days, 12 days) showed no significant changes in appearance, pH value, sodium benzoate and content compared with 0 day. The stability results of the mixed samples of raw materials and excipients were consistent with the stability results of the raw materials under the same storage conditions. The compatibility of the main drug and excipients was good.
[0028] Experiment 2: Stability study of samples with different sodium benzoate dosages
[0029] Prepare sodium benzoate with a concentration of 0.45 mg / ml (batch number: 230222-1): 10 g potassium chloride, 2 g glycerol and 0.072 g sucralose as flavoring agents, 0.045 g sodium benzoate as antibacterial agent, 0.16 g anhydrous citric acid and 0.24 g sodium citrate as pH adjusters, 0.04 g orange flavor as flavoring agent, 6 g sunset yellow as coloring agent, and 100 ml of purified water as solvent.
[0030] Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, and sodium benzoate to the above solution in turn, and stir until dissolved and clarified; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clarified; then add purified water to 100 ml, stir to dissolve, filter, and fill.
[0031] Sample of 0.5mg / ml (batch number: 230222-2): potassium chloride 10g, flavoring agents are glycerol 2g and sucralose 0.072g, antibacterial agent is sodium benzoate 0.05g, pH adjuster is anhydrous citric acid 0.16g and sodium citrate 0.24g, flavoring agent is orange flavor 0.04g, coloring agent is sunset yellow 6g, and solvent is purified water added to 100ml.
[0032] Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, and sodium benzoate to the above solution in turn, and stir until dissolved and clarified; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clarified; then add purified water to 100 ml, stir to dissolve, filter, and fill.
[0033] The key quality attributes of the samples were tested, and the stability of the samples was investigated by retaining samples of influencing factors. The test results were compared with the reference preparations, and the key quality attributes of the samples were not significantly different from the original research. The test results are shown in the table below.
[0034] Table 4 Stability test results of samples with different sodium benzoate concentrations
[0035]
[0036] Investigation on the antibacterial efficacy of samples with different sodium benzoate dosages
[0037] Sodium benzoate is used as an antibacterial agent in the prescription, with a dosage of 0.5 mg / ml. Samples were prepared according to the designed prescription to examine the antibacterial efficacy. The antibacterial efficacy of potassium chloride oral solution was developed and verified by methodology using the provisions of the "1121 Antibacterial Efficacy Test Method" in the General Rules of Part Four of the 2020 Edition of the Chinese Pharmacopoeia. Because sodium benzoate is pH-dependent and relatively inactive when the pH is greater than 5, in order to confirm whether the antibacterial efficacy of sodium benzoate samples meets the requirements under high pH conditions, pH4.5 samples were prepared to examine whether the antibacterial efficacy still meets the requirements; in order to confirm whether the antibacterial efficacy meets the requirements after the sodium benzoate content is reduced, samples with 90% of the prescription amount of sodium benzoate (concentration of 0.45 mg / ml) were prepared to examine whether the antibacterial efficacy still meets the requirements. The antibacterial efficacy of the tested samples all met the requirements. The test results are as follows.
[0038] Table 5 Antibacterial efficacy test results of sodium benzoate samples at different pH conditions
[0039]
[0040]
[0041] Test conclusion: The key quality attributes of the sample are consistent with the reference preparation, the stability is not significantly different from the reference preparation, the antibacterial efficacy of the sample meets the requirements, and the selected dosage of sodium benzoate is 0.5 mg / ml.
[0042] Content detection method: Take about 0.15g of this product, weigh accurately, add 50ml of water to dissolve, add 5ml of 2% dextrin solution, 2ml of 2.5% borax solution and 5-8 drops of fluorescent yellow indicator solution, and titrate with silver nitrate titration solution (0.1mol / L). Each 1ml of silver nitrate titration solution (0.1mol / L) is equivalent to 7.455mg of potassium chloride. Calculated on the basis of dry product, the potassium chloride content shall not be less than 99.5%.
[0043] Preparation Example
[0044] Example 1
[0045] Potassium chloride 100g, flavoring agents are glycerol 20g and sucralose 0.72g, antibacterial agent is sodium benzoate 0.5g, pH adjuster is anhydrous citric acid 1.6g and sodium citrate 2.4g, fragrance agent is orange flavor 0.4g, colorant is sunset yellow 60g, solvent is purified water added to 1000ml.
[0046] Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, and sodium benzoate to the above solution in sequence, and stir until dissolved and clarified; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clarified; then add purified water to 1000 ml, stir to dissolve, filter, and fill to obtain 10 bottles of oral solution.
[0047] Example 2
[0048] 50kg of potassium chloride, 10kg of glycerol and 0.36kg of sucralose are flavoring agents, 0.25kg of sodium benzoate is an antibacterial agent, 0.8kg of anhydrous citric acid and 1.2kg of sodium citrate are pH adjusting agents, 0.2kg of orange flavor is a fragrance agent, 30kg of sunset yellow is a coloring agent, and the solvent is purified water added to 500L.
[0049] Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, and sodium benzoate to the above solution in sequence, and stir until dissolved and clarified; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clarified; then add purified water to 500L, stir to dissolve, filter, and fill to obtain 5000 bottles of oral solution.
[0050] Stability test
[0051] Example 2 is placed horizontally, and the stability under high temperature (60°C) and light (illuminance 4500lx) conditions. The inspection results show that the appearance, pH value, sodium benzoate (mg / ml), and content (%) of the small test sample under high temperature, light, and accelerated conditions all meet the requirements, and the small test sample has good stability.
[0052] In addition, the solvent loss of the small test samples under accelerated conditions (40°C, RH20%) was investigated. The solvent losses of the small test samples at 10 days, 30 days, 2 months and 3 months were 0.025%, 0.061%, 0.107% and 0.157% respectively. The retention time and solvent loss were in positive proportion. The solvent loss at 3 months was about 0.157%, which was much less than 5% and met the requirements.
[0053] Table 6 Stability test results
[0054]
[0055] Table 7 Stability test results - solvent loss
[0056]
[0057]
[0058] Test conclusion: The above test shows that the potassium chloride oral solution of the present invention has good stability.
[0059] The above embodiments are only used to illustrate the present invention, but not to limit the present invention. Although the present invention is described in detail with reference to the embodiments, it should be understood by those skilled in the art that various combinations, modifications or equivalent substitutions of the technical solutions of the present invention do not depart from the spirit and scope of the technical solutions of the present invention, and should be included in the scope of the claims of the present invention.
Claims
1. A pharmaceutical composition containing potassium chloride, characterized in that The pharmaceutical composition comprises potassium chloride, a flavoring agent, an antibacterial agent, a pH adjusting agent, a flavoring agent, a coloring agent and a solvent.
2. A pharmaceutical composition containing potassium chloride according to claim 1, wherein the pharmaceutical composition comprises potassium chloride, the flavoring agents are glycerol and sucralose, the antibacterial agent is sodium benzoate, the pH adjusting agents are anhydrous citric acid and sodium citrate, the flavoring agent is orange flavor, the coloring agent is sunset yellow, and the solvent is purified water.
3. A pharmaceutical composition containing potassium chloride according to claim 1, wherein the pharmaceutical composition comprises 10 parts by weight of potassium chloride, 2 parts by weight of glycerol and 0.072 parts by weight of sucralose as flavoring agents, 0.05 parts by weight of sodium benzoate as an antibacterial agent, 0.16 parts by weight of anhydrous citric acid and 0.24 parts by weight of sodium citrate as a pH adjusting agent, 0.04 parts by weight of orange flavor as a flavoring agent, 6 parts by weight of sunset yellow as a coloring agent, and the solvent is purified water.
4. A pharmaceutical composition containing potassium chloride according to claim 3, characterized in that The pharmaceutical composition is prepared into a liquid preparation.
5. A pharmaceutical composition containing potassium chloride according to claim 3, characterized in that The pharmaceutical composition is prepared as an oral solution.
6. A pharmaceutical composition containing potassium chloride according to claim 5, wherein the preparation method of the oral solution is: Take potassium chloride and add purified water to dissolve completely; add glycerin, sucralose, sodium benzoate to the above solution in turn, stir until dissolved and clear; then add anhydrous citric acid, sodium citrate, orange flavor, pigment, and colorant until dissolved and clear; then add purified water, stir to dissolve, filter, and fill.