Ibuprofen composition suspension and preparation method thereof
By using a sieving method in the preparation of ibuprofen suspension, the problems of complex equipment and low production efficiency in the existing technology have been solved, and the uniformity of the drug solution and the production efficiency have been improved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-19
- Publication Date
- 2026-03-10
AI Technical Summary
The existing ibuprofen suspension preparation process requires sophisticated workshop equipment and complex mixing procedures, resulting in low production efficiency.
Xanthan gum and active pharmaceutical ingredient (API) are added to the mixing tank by sieving, and continuous sieving is used to ensure that the xanthan gum swells completely and the API is dispersed evenly, so that the content uniformity of the drug solution at different locations is within 2%.
It simplifies the feeding process, reduces equipment usage and cleaning needs, improves production efficiency, and ensures the uniformity of the liquid medicine.
Smart Images
Figure CN121622571A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of medicine preparation, and particularly relates to a composition of ibuprofen suspension and a preparation method thereof. BACKGROUND
[0002] Ibuprofen, chemical name: 2- (4-isobutylphenyl) propionic acid. Molecular formula: C13H18O2, structural formula as follows: Ibuprofen, also known as isobutylphenylpropionic acid, is an aryl propionic acid non-steroidal anti-inflammatory drug, which is a non-selective cyclooxygenase inhibitor, can reduce the synthesis of prostaglandin, and has antipyretic, analgesic and anti-inflammatory effects. Ibuprofen is a racemic mixture of S (+) and R (-) enantiomers. In vivo and in vitro studies have shown that the S (+) isomer is responsible for clinical activity.
[0003] Ibuprofen has good stability, and its dosage forms are usually divided into 10 types, including tablets, capsules, granules, syrup, suspension, suppositories, tea, cream, gel, oral solution and the like. Its effects are as follows: 1. It can relieve mild to moderate pain such as headache, toothache, joint pain and the like; 2. It can reduce body temperature and is suitable for discomfort caused by fever; 3. It can inhibit inflammatory reaction and reduce inflammatory symptoms such as redness and pain. The action characteristics are as follows: 1. Fast antipyretic effect. High fever above 39℃ must be treated with antipyretic therapy as soon as possible, and the antipyretic effect of ibuprofen on patients with body temperature above 39.2℃ is much better than that of other non-steroidal anti-inflammatory drugs. The antipyretic effect of ibuprofen is faster and more durable than that of acetaminophen and aspirin of the same dosage; 2. Strong analgesic effect. The analgesic effect of ibuprofen is 16-32 times that of traditional drugs such as aspirin, and even replaces morphine which has been used for more than 100 years, and is used for the treatment of toothache, postoperative pain and cancer pain.
[0004] The original research patent US05374659 discloses a suspension containing ibuprofen and a preparation method thereof. In the preparation process, xanthan gum, pregelatinized starch and 20% sucrose of the prescription amount are mixed to obtain a dry mixed mixture, then water and glycerol are mixed, the dry mixed mixture is added to the liquid, and the xanthan gum is dispersed by stirring, then sucrose is added, and after the sucrose is completely dissolved, polysorbate 80, anhydrous citric acid and sodium benzoate are added and dissolved by stirring. Then, the ibuprofen is added to the stirring tank through a 40-mesh sieve and stirred and mixed to disperse. Finally, the essence and pigment are added and stirred uniformly, and then the volume is adjusted. In addition to the conventional liquid preparation tank used in the oral liquid workshop, the mixing machine equipment with mixing function used in the oral solid preparation workshop is also required, which has high requirements for the workshop.
[0005] To this end, the present application proposes a suspension of ibuprofen composition and a preparation method thereof. SUMMARY
[0006] The present application aims to provide a suspension of ibuprofen composition and a preparation method thereof to solve the problems raised in the background art.
[0007] To achieve the above-mentioned object, the present application provides the following technical solution: a suspension of ibuprofen composition, the raw material formula comprising 20 g / L of ibuprofen, 13.1 g / L of pregelatinized starch, 2.2 g / L of xanthan gum, 300 g / L of sucrose, 100 g / L of glycerol, 2 g / L of sodium benzoate, 1.8 g / L of anhydrous citric acid, 0.5 g / L of polysorbate 80, 0.005 g / L of alluring red, 0.025 g / L of sunset yellow, 0.561 g / L of orange essence, and 0.208 g / L of strawberry essence.
[0008] A preparation method of a suspension of ibuprofen composition, using the above-mentioned raw material formula, the specific method comprising: S1: adding 60% of the prescription amount of purified water to the liquid preparation tank, slowly adding pregelatinized starch under stirring, after the addition is completed, stirring for ≥10 min; turning on the heating to gelatinize the pregelatinized starch; S2: adding the prescription amount of sucrose to the liquid preparation tank, stirring for 10 min to make it completely dissolved; S3: turning on the tank cooling, when the temperature of the liquid medicine is cooled to ≤50℃, slowly adding xanthan gum through a 40-mesh screen into the stirring tank under stirring, after the addition is completed, continuing to stir for ≥30 min, then turning on the self-circulation through a 5-mm screen for 30 min, and then replacing the 20-mesh screen to continue the circulation stirring for 30-60 min; S4: after the swelling of the xanthan gum is completed, adding glycerol into the stirring tank under the stirring and circulation, and continuing to stir and circulate for 5 min; S5: continuing to add sodium benzoate, anhydrous citric acid, and polysorbate 80 into the stirring tank, and continuing to stir and circulate for 10 min to make them dissolved; S6: slowly adding ibuprofen through a screen into the stirring tank under stirring and circulation, after the addition of the raw medicine is completed, continuing to stir and circulate for ≥90 min, and then stopping; S7: adding sunset yellow, alluring red, orange essence, and strawberry essence into the stirring tank, and stirring and circulating for ≥30 min; S8: according to the content of the concentrated liquid, adding water to make the suspension reach the final volume, and stirring and circulating for ≥30 min to obtain an intermediate product; S9: calculating the weight of the liquid medicine for filling according to the relative density and the filling amount, and performing the filling.
[0009] Preferably, in S6, the mesh number of the circulating screen is 20.
[0010] Preferably, in the S1, the temperature of the liquid heating reaches 90±5℃, and the heating is stopped.
[0011] Preferably, in the S6, the mesh size of the screen for sieving ibuprofen is 40 mesh.
[0012] Compared with the prior art, the present application has the following beneficial effects: In the present application, the xanthan gum and the raw drug are added to the stirring tank by sieving, and the drug solution is sieved by continuous circulation to ensure that the xanthan gum is completely swollen and the raw drug is uniformly dispersed, so that the content uniformity RSD% of the drug solution at different positions is within 2%, and the drug solution has good uniformity. The present application simplifies the feeding process to a certain extent, reduces the use and cleaning of equipment, and improves the production efficiency. BRIEF DESCRIPTION OF DRAWINGS
[0013] Figure 1 The present application is a flowchart. DETAILED DESCRIPTION
[0014] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.
[0015] Embodiment 1 Table 1 Prescription confirmation information Please refer to Figure 1 Suspension preparation steps: S1: Add 60% of the prescription amount of purified water to the liquid preparation tank, slowly add pregelatinized starch under stirring, and after the addition is completed, stir for ≥10 min; turn on the heating, and when the temperature of the liquid reaches 90±5℃, stop heating to make the pregelatinized starch gelatinize; S2: Add the prescription amount of sucrose to the liquid preparation tank, and stir for 10 min to make it completely dissolved; S3: Turn on the tank cooling, and when the temperature of the liquid is ≤50℃, slowly add the xanthan gum to the stirring tank through a 40-mesh screen under stirring, and after the addition is completed, continue stirring for ≥30 min, then turn on the self-circulation through a 5-mm screen for 30 min, and then replace the 20-mesh screen to continue the stirring and circulation for 30-60 min; S4: After the swelling of the xanthan gum is completed, add glycerol to the stirring tank under the condition of maintaining the stirring and circulation, and continue stirring and circulation for 5 min; S5: Continue to add sodium benzoate, anhydrous citric acid and polysorbate 80 to the stirring tank, and continue to stir and circulate for 10 min to make them dissolved; S6: Ibuprofen was slowly added to the stirring tank through a 40-mesh sieve under stirring circulation. After the addition of the raw material was completed, the stirring circulation was continued for ≥90 min before stopping (circulation sieve mesh: 20 mesh).
[0016] S7: Sunset yellow, temptation red, orange essence, and strawberry essence were added to the stirring tank, and the stirring circulation was continued for ≥30 min. S8: Water was added to the concentrated liquid according to the content to make the suspension reach the final volume, and the stirring circulation was continued for ≥30 min to obtain an intermediate product. S9: The weight of the liquid to be filled was calculated according to the relative density and the filling amount, and filling was performed.
[0017] Example 2 The prescription was the same as in Example 1, and the liquid preparation steps were as follows: S1: Xanthan gum and 14% of the total weight of sucrose were placed in a square cone mixer and mixed for 20-30 min, and the mixture was taken out. S2: The prescription amount of 60% purified water was added to the liquid preparation tank, and pre-gelatinized starch was slowly added under stirring. After the addition was completed, stirring was continued for ≥10 min. Heating was started, and the temperature of the liquid reached 90±5°C. The heating was stopped, and the pre-gelatinized starch was gelatinized. S3: The prescription amount of sucrose was added to the liquid preparation tank, and stirring was continued for 10 min to make it completely dissolved. S4: When the temperature of the liquid was cooled to ≤50°C, the mixture of xanthan gum and sucrose was slowly added to the stirring tank under stirring. After the addition was completed, stirring was continued for ≥30 min. A 5-mesh sieve was started to circulate for 30 min, and then a 20-mesh sieve was replaced to continue stirring for 30-60 min. S5: Glycerol was added to the stirring tank under stirring circulation, and stirring was continued for 5 min. S6: Sodium benzoate, anhydrous citric acid, and polysorbate 80 were continuously added to the stirring tank, and stirring was continued for 10 min to make them dissolved. S7: Ibuprofen was slowly added to the stirring tank through a 40-mesh sieve under stirring circulation. After the addition of the raw material was completed, the stirring circulation was continued for ≥90 min before stopping (circulation sieve mesh: 20 mesh).
[0018] S8: Sunset yellow, temptation red, orange essence, and strawberry essence were added to the stirring tank, and the stirring circulation was continued for ≥30 min. S9: Water was added to the concentrated liquid according to the content to make the suspension reach the final volume, and the stirring circulation was continued for ≥30 min to obtain an intermediate product. S10: The weight of the liquid to be filled was calculated according to the relative density and the filling amount, and filling was performed.
[0019] Example 3 The prescription is the same as that of Example 1, and the solution preparation step is as follows: S1: Add 60% of the purified water of the prescription amount to the solution preparation tank, slowly add the pregelatinized starch under stirring, after the addition is completed, stir for ≥10 min; turn on the heating, and when the temperature of the solution reaches 90±5℃, stop heating and gelatinize the pregelatinized starch; S2: Add the prescription amount of sucrose to the solution preparation tank, and stir for 10 min to make it completely dissolved; S3: Turn on the tank cooling, and when the temperature of the solution cools down to ≤50℃, slowly add the xanthan gum through a 40-mesh sieve into the stirring tank under stirring, after the addition is completed, continue stirring for ≥30 min, and then turn on the self-circulation for ≥3 h; S4: After the swelling of the xanthan gum is completed, add the glycerol into the stirring tank under the condition of maintaining the stirring and circulation, and continue stirring and circulating for 5 min; S5: Continue to add the sodium benzoate, anhydrous citric acid and polysorbate 80 into the stirring tank, and continue to stir and circulate for 10 min to make them dissolved; S6: Slowly add the ibuprofen through a 40-mesh sieve into the stirring tank under the condition of stirring and circulation, after the addition of the drug substance is completed, continue stirring and circulating for ≥2 h, and then stop.
[0020] S7: Add sunset yellow, temptation red, orange essence and strawberry essence into the stirring tank, and stir and circulate for ≥30 min; S8: According to the content of the concentrated solution, add water to make the suspension reach the final volume, and stir and circulate for ≥30 min to obtain the intermediate product; S9: Calculate the weight of the filling solution according to the relative density and the filling volume, and perform the filling.
[0021] The samples at different positions after constant volume in the above Examples 1-3 are detected for the content, and the mixing uniformity is investigated, and the investigation results are as follows: Conclusion 1: In Example 1, the xanthan gum is not mixed with sucrose in advance before feeding, but is added into the stirring tank through a 40-mesh sieve in the same way as the drug substance, after the addition of the xanthan gum is completed, continue stirring for ≥30 min, then turn on the self-circulation through a 5-mm sieve for 30 min, and then replace the 20-mesh sieve to continue the stirring and circulation for 30-60 min; the drug substance is also slowly added into the stirring tank through a 40-mesh sieve, after the addition of the drug substance is completed, continue stirring and circulating for ≥90 min, and then stop (the mesh number of the circulating sieve: 20 mesh), the whole preparation process is smooth, the content detection results at different positions after constant volume and stirring and circulation for 30 min have an RSD% of <2%, and the xanthan gum and ibuprofen can ensure the uniformity of the solution after being fed and dispersed / swollen in the above way.
[0022] Conclusion 2: The xanthan gum of Example 2 is mixed with part of the prescribed amount of sucrose in advance before feeding, and then added to the stirring tank. After the mixture is added, the stirring is continued for ≥30 min, and then the self-circulation is started for 5 mm screen for 30 min, and then the 20 mesh screen is replaced for continued stirring and circulation for 30-60 min. The raw material is also slowly added to the stirring tank by passing through a 40 mesh screen. After the raw material is added, the stirring and circulation is continued for ≥90 min, and then stopped (circulation screen mesh: 20 mesh). The whole preparation process is smooth, and the content detection results RSD% of different positions after final volume setting and stirring for 30 min are <2%. The xanthan gum and ibuprofen can also ensure the uniformity of the liquid medicine by the above feeding, dispersion / swelling method. Compared with Example 1, there is an additional mixing process, and the mixture does not need to pass through a 40 mesh screen when added to the stirring tank. This is a higher requirement for the production workshop, and a mixing machine with appropriate volume must be provided. Conclusion 3: The feeding method of xanthan gum and raw material of Example 3 is consistent with Example 1, but the xanthan gum and raw material do not pass through a screen during the stirring and circulation dispersion / swelling process. The whole preparation time is longer. The content detection results RSD% of different positions after final volume setting and stirring for 30 min are qualified but slightly high, and there is a certain risk of liquid medicine uniformity.
[0023] Although the embodiments of the present application have been shown and described in detail, as described above, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.
Claims
1. A suspension of a composition of ibuprofen, characterized in that, The raw material formula includes ibuprofen 20 g / L, pregelatinized starch 13.1 g / L, xanthan gum 2.2 g / L, sucrose 300 g / L, glycerol 100 g / L, sodium benzoate 2 g / L, anhydrous citric acid 1.8 g / L, polysorbate 80 0.5 g / L, temptation red 0.005 g / L, sunset yellow 0.025 g / L, orange essence 0.561 g / L, strawberry essence 0.208 g / L.
2. A process for the preparation of a suspension of a composition of ibuprofen, characterized in that, The specific method includes the following steps: S1: adding 60% of the purified water in the prescription amount to the liquid preparation tank, slowly adding the pregelatinized starch under stirring, and stirring for ≥10 min after the addition is completed; turning on the heating to gelatinize the pregelatinized starch; S2: adding the sucrose in the prescription amount to the liquid preparation tank, and stirring for 10 min to completely dissolve; S3: turning on the tank cooling to cool the liquid temperature to ≤50℃, slowly adding the xanthan gum to the stirring tank through a 40-mesh screen under stirring, continuing to stir for ≥30 min after the addition is completed, turning on the self-circulation through a 5-mm screen for 30 min, and then replacing the 20-mesh screen to continue the stirring and circulation for 30-60 min; S4: after the swelling of the xanthan gum is completed, adding the glycerol to the stirring tank under the stirring and circulation, and continuing to stir and circulate for 5 min; S5: continuing to add the sodium benzoate, the anhydrous citric acid and the polysorbate 80 to the stirring tank, and continuing to stir and circulate for 10 min to dissolve; S6: slowly adding the ibuprofen to the stirring tank through a screen under stirring and circulation, and stopping after continuing to stir and circulate for ≥90 min after the addition of the raw material is completed; S7: adding the sunset yellow, the temptation red, the orange essence and the strawberry essence to the stirring tank, and stirring and circulating for ≥30 min; S8: adding water according to the content of the concentrated liquid to make the suspension reach the final volume, and stirring and circulating for ≥30 min to obtain the intermediate product; S9: calculating the weight of the liquid to be filled according to the relative density and the filling amount, and performing the filling.
3. A process for the preparation of a suspension of ibuprofen composition as claimed in claim 2, wherein, In S6, the mesh number of the circulating screen is 20.
4. A process for the preparation of a suspension of ibuprofen composition as claimed in claim 2, wherein, In S1, the temperature of the liquid heating reaches 90±5℃, and the heating can be stopped.
5. A process for the preparation of a suspension of ibuprofen composition as claimed in claim 2, wherein, In S6, the mesh number of the screen for sieving the ibuprofen is 40.