Isobutylphenylpropionic acid suspension drop and preparation method thereof
By using xanthan gum with different particle sizes, the problem of poor stability in isobutylphenylpropionic acid liquid formulations was solved, resulting in improved stability and user experience of the suspension drops.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-29
- Publication Date
- 2026-03-31
AI Technical Summary
Existing isobutylphenylpropionic acid liquid formulations have poor stability, especially suspension drops, which affects the safety and efficacy of the medication for patients.
Xanthan gum of different particle sizes was used as a thickener and suspending agent, and was formulated into a suspension droplet with isobutylphenylpropionic acid and other excipients. The suspension droplet consisted of xanthan gum 1 with a D90 of 10-40 μm and xanthan gum 2 with a D90 of 150-220 μm, in a ratio of 1.5 to 3.5:1.
This improves the stability of the suspension drops, making the product less prone to sedimentation and ensuring the long-term stability of the drug and the user experience.
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Abstract
Description
Technical Field
[0001] This application belongs to the field of pharmaceutical formulation technology, and more specifically, relates to an isobutylphenylpropionic acid suspension drop and its preparation method. Background Technology
[0002] Ibuprofen, also known as isobutylphenylpropionic acid, is a commonly used antipyretic and analgesic drug for children, primarily used to reduce fever in infants and young children and to relieve mild headaches, sore throats, and toothaches caused by colds, influenza, etc. Ibuprofen suspension exerts its antipyretic and analgesic effects by inhibiting the synthesis of prostaglandins in the body. Specifically, it mainly acts on the central nervous system and inflamed tissues, reducing prostaglandin synthesis by inhibiting the activity of cyclooxygenase. Prostaglandins are important inflammatory mediators that can cause fever, pain, and inflammatory responses. Therefore, by inhibiting prostaglandin synthesis, isobutylphenylpropionic acid can effectively lower body temperature, relieve pain, and reduce inflammation.
[0003] Isobutylphenylpropionic acid is available in various dosage forms, including tablets, capsules, and granules. However, for children and elderly people with swallowing difficulties, liquid formulations remain the first choice due to their ease of administration and rapid onset of action. However, isobutylphenylpropionic acid has poor water solubility; this water-insoluble active drug is prone to sedimentation, stratification, or even flocculation in liquid formulations, making it difficult to prepare stable and readily usable isobutylphenylpropionic acid liquid formulations. This is especially true for suspension drops, a thermodynamically and kinetically unstable system, where product stability cannot be guaranteed, impacting patient safety and efficacy. Summary of the Invention
[0004] This application provides an isobutylphenylpropionic acid suspension drop, which has stable performance and better condition.
[0005] This application provides an isobutylphenylpropionic acid suspension drop, comprising, by weight percentage: 4% isobutylphenylpropionic acid, 1.18-1.66% xanthan gum 1 and xanthan gum 2, 0%-0.075% polysorbate 80, 0.18% anhydrous citric acid, 0.2% sodium benzoate, 30% sucrose, 10% glycerin, 0.04% fragrance, and 53.845-54.4% water; the D90 of xanthan gum 1 is 10-40 μm, and the D90 of xanthan gum 2 is 150-220 μm.
[0006] In one specific embodiment of the present invention, the ratio of xanthan gum 1 to xanthan gum 2 is 1.5 to 3.5:1.
[0007] In one specific embodiment of the present invention, the ratio of xanthan gum 1 to xanthan gum 2 is 2:1.
[0008] In one specific embodiment of the present invention, the particle size D90 of xanthan gum 1 is 30 μm.
[0009] In one specific embodiment of the present invention, the particle size D90 of xanthan gum 2 is 180 μm.
[0010] In one specific embodiment of the present invention, the particle size D90 of xanthan gum 1 is 30 μm, the particle size D90 of xanthan gum 2 is 180 μm, and the ratio of xanthan gum 1 to xanthan gum 2 is 2:1.
[0011] In one specific embodiment of the present invention, the total weight ratio of xanthan gum 1 to xanthan gum 2 is 1.44%.
[0012] This invention also provides a method for preparing isobutylphenylpropionic acid suspension drops, comprising:
[0013] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0014] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0015] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0016] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0017] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0018] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0019] 7) Let stand to remove air bubbles, then fill into containers to obtain the final product.
[0020] Beneficial effects:
[0021] Xanthan gum plays a crucial role in improving viscosity, maintaining stability, and enhancing the user experience of isobutylphenylpropionic acid (ABSA) suspension drops. The inventors conducted experiments with xanthan gum of different particle sizes and unexpectedly discovered that changes in particle size significantly affect the stability of ABSA suspension drops. This invention utilizes a compound of two xanthan gums with different particle sizes as a thickener and suspending agent, formulated together with the active ingredient ABSA and other excipients to create an ABSA suspension drop with stable performance and improved consistency. Detailed Implementation
[0022] The technical solutions in the embodiments of this application are clearly described below. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.
[0023] The terms "first," "second," etc., used in the specification and claims of this application are used to distinguish similar objects and not to describe a specific order or sequence. Furthermore, the words "and / or" in the specification and claims indicate at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.
[0024] This application is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of this application.
[0025] This application provides an isobutylphenylpropionic acid suspension drop, comprising, by weight percentage: 4% isobutylphenylpropionic acid, 1.18-1.66% xanthan gum 1 and xanthan gum 2, 0%-0.075% polysorbate 80, 0.18% anhydrous citric acid, 0.2% sodium benzoate, 30% sucrose, 10% glycerin, 0.04% fragrance, and 53.845-54.4% water; the D90 of xanthan gum 1 is 10-40 μm, and the D90 of xanthan gum 2 is 150-220 μm. The D90 of xanthan gum 1 can be 10 μm, 30 μm, or 40 μm, and the D90 of xanthan gum 2 can be 150 μm, 200 μm, or 220 μm.
[0026] In one specific embodiment of the present invention, the ratio of xanthan gum 1 to xanthan gum 2 is 1.5 to 3.5:1, and the ratio of xanthan gum 1 to xanthan gum 2 can be 1.5:1, 2:1, or 3.5:1.
[0027] In one specific embodiment of the present invention, the particle size D90 of xanthan gum 1 is 30 μm, the particle size D90 of xanthan gum 2 is 180 μm, and the ratio of xanthan gum 1 to xanthan gum 2 is 2:1.
[0028] In one specific embodiment of the present invention, the total weight ratio of xanthan gum 1 to xanthan gum 2 is 1.44%.
[0029] This invention also provides a method for preparing isobutylphenylpropionic acid suspension drops, comprising:
[0030] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0031] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0032] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0033] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0034] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0035] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0036] 7) Let stand to remove air bubbles, then fill into containers to obtain the final product.
[0037] The isobutylphenylpropionic acid suspension drops prepared by the method provided in this invention are stable and do not easily settle.
[0038] The sources and standards of raw materials and auxiliary materials used in the following embodiments and comparative examples are shown in Table 1.
[0039] Table 1. Sources and Standards of Raw and Auxiliary Materials
[0040] name Manufacturer Implementation Standards Isobutylphenylpropionic acid Shandong Xinhua Pharmaceutical Co., Ltd. Internal control standard filing registration number Y20180001074 Xanthan Gum Jiangsu Shenhua Pharmaceutical Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV glycerin Jiangxi Hanjiang Pharmaceutical Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV sucrose Shijiazhuang Qianxu Pharmaceutical Technology Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV Anhydrous citric acid Shijiazhuang Qianxu Pharmaceutical Technology Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV Sodium benzoate Shijiazhuang Qianxu Pharmaceutical Technology Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV Polysorbate 80 Guangdong Runhua Chemical Co., Ltd. Chinese Pharmacopoeia 2020 Edition, Part IV strawberry flavoring Mans (Shanghai) Flavors & Fragrances Co., Ltd. National Standard GB30616 Purified water - Chinese Pharmacopoeia 2020 Edition, Part IV
[0041] Example 1
[0042] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 2.
[0043] Table 2 Raw and auxiliary materials used in Example 1
[0044]
[0045] 2) Preparation process:
[0046] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0047] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0048] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0049] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0050] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0051] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0052] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 1.
[0053] Example 2
[0054] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 3.
[0055] Table 3 Raw and auxiliary materials used in Example 2
[0056]
[0057] 2) Preparation process:
[0058] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0059] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0060] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0061] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0062] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0063] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0064] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 2.
[0065] Example 3
[0066] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 4.
[0067] Table 4 Raw and auxiliary materials used in Example 3
[0068]
[0069] 2) Preparation process
[0070] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0071] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0072] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0073] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0074] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0075] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0076] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 3.
[0077] Example 4
[0078] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 5.
[0079] Table 5. Raw and auxiliary materials used in Example 4
[0080]
[0081]
[0082] 2) Preparation process
[0083] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0084] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0085] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0086] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0087] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0088] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0089] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 4.
[0090] Example 5
[0091] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 6.
[0092] Table 6 Raw and auxiliary materials used in Example 5
[0093]
[0094]
[0095] 2) Preparation process
[0096] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0097] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0098] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0099] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0100] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0101] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0102] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 5.
[0103] Example 6
[0104] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 7.
[0105] Table 7 Raw and auxiliary materials used in Example 6
[0106]
[0107] 2) Preparation process
[0108] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0109] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0110] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0111] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0112] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0113] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0114] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 6.
[0115] Example 7
[0116] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 8.
[0117] Table 8 Raw and auxiliary materials used in Example 7
[0118]
[0119] 2) Preparation process
[0120] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0121] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0122] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0123] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0124] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0125] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0126] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 7.
[0127] Comparative Example 1
[0128] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 9.
[0129] Table 9. Raw and auxiliary materials used in Comparative Example 1
[0130]
[0131] 2) Preparation process
[0132] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0133] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0134] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0135] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0136] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0137] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0138] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 8.
[0139] Comparative Example 2
[0140] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 10.
[0141] Table 10 Raw and auxiliary materials used in Comparative Example 2
[0142]
[0143] 2) Preparation process
[0144] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0145] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0146] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0147] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0148] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0149] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0150] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 9.
[0151] Comparative Example 3
[0152] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 11.
[0153] Table 11 Raw and auxiliary materials used in Comparative Example 3
[0154]
[0155]
[0156] 2) Preparation process
[0157] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0158] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0159] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0160] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0161] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0162] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0163] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 10.
[0164] Comparative Example 4
[0165] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 12.
[0166] Table 12 Raw and auxiliary materials used in Comparative Example 4
[0167]
[0168]
[0169] 2) Preparation process
[0170] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0171] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0172] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0173] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0174] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0175] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0176] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 11.
[0177] Comparative Example 5
[0178] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 13.
[0179] Table 13 Raw and auxiliary materials used in Comparative Example 5
[0180]
[0181] 2) Preparation process
[0182] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0183] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0184] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0185] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0186] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0187] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0188] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 12.
[0189] Comparative Example 6
[0190] 1) Weighing: Weigh the raw materials and excipients according to the prescription amount, see Table 14.
[0191] Table 14 Raw and auxiliary materials used in Comparative Example 6
[0192]
[0193] 2) Preparation process
[0194] 1) Mix xanthan gum 1 with glycerin, then add an appropriate amount of purified water and stir to make it swell;
[0195] 2) Add xanthan gum 2 to an appropriate amount of purified water and stir to disperse evenly;
[0196] 3) Add sucrose, anhydrous citric acid, sodium benzoate, and flavoring to an appropriate amount of purified water and homogenize until dissolved;
[0197] 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1) and stir until homogeneous;
[0198] 5) Dissolve polysorbate 80 in an appropriate amount of purified water, then add isobutylphenylpropionic acid and stir well, then homogenize.
[0199] 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir well, add the remaining purified water to make up to 100%, and mix well;
[0200] 7) Let stand to remove air bubbles, then fill into containers to obtain drops 13.
[0201] Table 3 shows a list of variables in Examples 1-7 and Comparative Examples 1-6.
[0202] Table 3. A list of variables in Examples 1-7 and Comparative Examples 1-6
[0203]
[0204] The stability of drops 1-13 prepared in Examples 1-7 and Comparative Examples 1-6 was tested.
[0205] Test method:
[0206] Take drops 1-13, and use the original isobutylphenylpropionic acid suspension drops (Shanghai Johnson & Johnson Pharmaceutical Co., Ltd., trade name: Motrin) as a reference. Take about 7 ml of each sample and place it in a 10 ml glass bottle. Seal the bottle and place it under the conditions of room temperature, high temperature 40℃, high temperature 60℃, and light irradiation of 4500 lx for 60 days to observe the changes in appearance.
[0207] Room temperature: Place one sample bottle at room temperature (25-30℃), take samples for observation after 60 days, and continue to store for up to 12 months.
[0208] High temperature 60℃: Place one bottle of sample in an electric thermostatic drying oven (DHG-9070A type) set at 60℃, and take samples for observation after 60 days;
[0209] Illumination at 4500 lx: Place one sample bottle in a clarity meter (CM-III type), adjust the light intensity to 4500 lx, and take samples for observation after 60 days.
[0210] The appearance of the above isobutylphenylpropionic acid suspension drops was observed, and the pH value, viscosity, content and related substances were tested. The test results are shown in Table 4.
[0211] Table 4. Results of test parameters for drops 1-13 under different environments and at different times.
[0212]
[0213]
[0214] From observing Table 4, we can draw the following conclusions:
[0215] 1) Observation of drops 1-3 and drops 8-9 shows that drops 1-3 have good stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ with 4500 lx light, the properties of the drops did not change, and the changes in pH, active substance content, and related substance content were also relatively small. Drops 8-9 have relatively poor stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ with 4500 lx light, the drops showed flocculent matter and sedimentation, and the changes in pH, active substance content, and related substance content were significant. Therefore, under the same conditions, the isobutylphenylpropionic acid suspension drops prepared with xanthan gum 1 having a particle size D90 of 10-40 μm have better stability.
[0216] 2) Observation of drops 4-5 and drops 10-11 shows that drops 4-5 have good stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ with 4500lx light, the properties of the drops did not change, and the changes in pH value, active substance content, and related substance content were also relatively small. Drops 10-11 have relatively poor stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ with 4500lx light, the drops showed flocculent matter and sedimentation, and the changes in pH value, active substance content, and related substance content were significant. Therefore, under the same conditions, the isobutylphenylpropionic acid suspension drops prepared with xanthan gum 2 having a particle size D90 of 150-220μm have better stability.
[0217] 3) Observation of drops 6-7 and drops 12-13 shows that drops 6-7 have good stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ and 4500lx light, the properties of the drops did not change, and the changes in pH value, active substance content, and related substance content were also relatively small. Drops 12-13 have relatively poor stability. After 12 months of storage at room temperature and 60 days of accelerated testing at 60℃ and 4500lx light, the drops showed flocculent matter and sedimentation, and the changes in pH value, active substance content, and related substance content were relatively large. Therefore, under the same conditions, the stability of isobutylphenylpropionic acid suspension drops is better when the ratio of xanthan gum 1 to xanthan gum 2 is 1.5-3.5:1.
[0218] It is understood that the above embodiments are merely exemplary implementations used to illustrate the principles of this application, and this application is not limited thereto. For those skilled in the art, various modifications and improvements can be made without departing from the spirit and substance of this application, and these modifications and improvements are also considered to be within the scope of protection of this invention.
Claims
1. An ibuprofen suspension drop preparation, characterized in that, According to the percentage by weight, including: isobutyl ibuprofen 4%, xanthan gum 1 and xanthan gum 2 account for 1.18-1.66%, polysorbate 80 0%-0.075%, anhydrous citric acid 0.18%, sodium benzoate 0.2%, sucrose is 30%, glycerol is 10%, essence 0.04%, water 53.845-54.4%; The D90 of the xanthan gum 1 is 10-40μm, and the D90 of the xanthan gum 2 is 150-220μm.
2. A ibuprofen suspension drop preparation according to claim 1, wherein The amount ratio of the xanthan gum 1 to the xanthan gum 2 is 1.5~3.5:
1.
3. The ibuprofen suspension drops according to claim 1, wherein The amount ratio of the xanthan gum 1 to the xanthan gum 2 is 2:
1.
4. The ibuprofen suspension drops according to claim 1, wherein The particle size D90 of the xanthan gum 1 is 30μm.
5. The ibuprofen suspension drops according to claim 1, wherein The particle size D90 of the xanthan gum 2 is 180μm.
6. A ibuprofen suspension drop preparation according to claim 1, wherein The particle size D90 of the xanthan gum 1 is 30μm, and the particle size D90 of the xanthan gum 2 is 180μm, and the amount ratio of the xanthan gum 1 to the xanthan gum 2 is 2:
1.
7. The ibuprofen suspension drops according to claim 1, wherein The total weight ratio of the xanthan gum 1 to the xanthan gum 2 is 1.44%.
8. The ibuprofen suspension drops according to claim 1, wherein Including: Isobutyl ibuprofen 4%, xanthan gum 1 and xanthan gum 2 account for 1.44%, polysorbate 80 0.05%, anhydrous citric acid 0.18%, sodium benzoate 0.2%, sucrose is 30%, glycerol is 10%, essence 0.04%, water 53.845-54.4%.
9. A process for the preparation of ibuprofen suspension drops as claimed in any one of claims 1 to 8, characterized in that, Including: 1) Mix the xanthan gum 1 and glycerol uniformly, then add appropriate purified water and stir to swell; 2) Add the xanthan gum 2 to appropriate purified water and stir to disperse uniformly; 3) Add sucrose, anhydrous citric acid, sodium benzoate, and essence to appropriate purified water, and homogenize to dissolve; 4) Add the solutions obtained in steps 2) and 3) to the solution obtained in step 1), and stir uniformly; 5) Dissolve polysorbate 80 in appropriate purified water, then add isobutyl ibuprofen and stir, and then homogenize; 6) Add the solution obtained in step 5) to the solution obtained in step 4), stir uniformly, add the remaining purified water to make up to 100%, and mix uniformly; 7) Remove bubbles by standing, fill, and obtain.