Ibuprofen suspension and preparation method thereof

Abstract

The invention provides an ibuprofen suspension and a preparation method thereof, the ibuprofen suspension comprises 2.0-5.0% of ibuprofen and 0.1-0.5% of karaya gum, and also comprises 2-4% of a sweetening agent and 0.5-2.0% of a suspending aid, the suspending aid is selected from one or more of sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose and sodium alginate, and the suspending aid is selected from one or more of sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose and sodium alginate. The sweetening agent is selected from one or more of cane sugar, stevioside and proteoglycan, the pH value of the suspension is 4.5-5.5, a specific auxiliary material adding sequence is adopted, and the suspension has excellent acid stability and pH adaptability, more excellent suspension capacity and pure natural and unique rheological characteristics.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, in particular to a suspension of ibuprofen and a preparation method thereof. BACKGROUND

[0002] Ibuprofen is an effective non-steroidal anti-inflammatory drug, widely used for antipyretic and analgesic in children and adults. Due to its extremely low solubility in water, it is usually formulated as a suspension to facilitate administration. However, ibuprofen suspension has long been plagued by physical stability problems, such as particle settling, caking, difficulty in re-dispersion, and poor mouthfeel (gritty sensation), which directly affect the accuracy of medication and patient compliance.

[0003] Xanthan gum is commonly used as a suspension stabilizer in the prior art. Xanthan gum can form a three-dimensional network structure, effectively slowing down particle settling. However, conventional xanthan gum has the following inherent defects: 1) its suspending ability is limited in low ionic strength environments, and slow settling may still occur; 2) its solution has a certain "pseudo-plasticity", with high viscosity when standing, which may cause difficulty in pouring, while the viscosity rapidly decreases after stirring or shaking, although it is easy to take, but once standing, the newly established network structure may not be sufficient to completely prevent the flocculation and settling of fine particles; 3) the wettability and steric hindrance effect on the surface of ibuprofen particles are not ideal.

[0004] To solve these problems, the prior art often uses a composite stabilization system, for example, the ibuprofen suspension in CN119606878A includes ibuprofen, microcrystalline cellulose, stearate and citrate, or the one in CN112516083B contains a prescription amount of ibuprofen, xanthan gum, glycerol, soluble starch, sucrose, anhydrous citric acid, polysorbate, sodium benzoate, allura red, sunset yellow, orange flavor, strawberry flavor and purified water, and the ibuprofen has a particle size in the range of 35-65 μm. These methods have improved stability to some extent, but have increased the complexity of the formula and may introduce new problems, such as microcrystalline cellulose may cause bad mouthfeel, and xanthan gum may adsorb drugs affecting bioavailability. Therefore, there is an urgent need in the art for a new technology of ibuprofen suspension with simpler formula, more outstanding stability, and significantly improved mouthfeel. SUMMARY

[0005] The present application relates to a suspension of ibuprofen and a preparation method thereof.

[0006] A suspension of ibuprofen, comprising: 2.0-5.0% of ibuprofen and 0.1-0.5% of gum from the genus Anogeissus, based on the total weight of the suspension.

[0007] The ibuprofen suspension also contains 2-4% sweetener and 0.5-2.0% suspending agent selected from one or more of sodium carboxymethylcellulose, hydroxypropyl methylcellulose and sodium alginate.

[0008] The ibuprofen suspension, the sweetener is selected from one or more of sucrose, stevioside and acesulfame potassium.

[0009] The ibuprofen suspension, the pH of the suspension is 4.5-5.5.

[0010] The method for preparing the ibuprofen suspension comprises the following steps:

[0011] a) dispersing the gum and the suspending agent in part of purified water under heating and stirring to form an aqueous phase colloid;

[0012] b) dissolving the sweetener in part of purified water to form a sugar syrup;

[0013] c) mixing the sugar syrup obtained in step b) with the aqueous phase colloid obtained in step a);

[0014] d) adding ibuprofen to the mixture obtained in step c) and stirring to disperse uniformly;

[0015] e) adding a preservative and a flavoring agent and adjusting the pH of the system;

[0016] f) adjusting the volume, homogenizing to obtain the final product.

[0017] The method, the heating temperature in step a) is 70-80℃.

[0018] The method, the homogenization in step f) adopts high-pressure homogenization method, the pressure is 20-50 MPa, and the cycle is 1-3 times.

[0019] The present application provides an ibuprofen suspension and a preparation method thereof, which has the following beneficial effects:

[0020] 1. The present application has excellent acid stability and pH adaptability: ibuprofen suspension is usually an acidic system (pH about 4.0-5.0) to maintain the solubility of ibuprofen and reduce the discomfort of taste. The gum is very stable in acidic environment, and its viscosity and suspension capacity will not decrease significantly. Although xanthan gum is also relatively stable under acidic conditions, the gum performs better, especially in long-term resistance to acidic environment, which is crucial to ensure the stability of the drug during the entire shelf life.

[0021] 2. Superior suspending ability: Kari gum can form a high viscosity, high yield value gel network structure. This means that, in a static state, it can provide enough internal strength to support the ibuprofen particles, almost completely eliminating the "top water separation" phenomenon, and effectively preventing the formation of hard, not easy to re-disperse sediment. Xanthan gum has good suspending ability, but its solution is more of a pseudoplastic fluid, with a relatively low yield value. Under long-term static or temperature fluctuations, the risk of slight water separation or the formation of soft sediment is higher than that of the Kari gum system.

[0022] 3. Pure natural: Kari gum is a pure natural plant-derived colloid, and xanthan gum is produced by microbial fermentation (Xanthomonas campestris), although it is safe, but it is not as good as Kari gum in terms of "natural" attributes.

[0023] 4. Unique rheological properties: Kari gum solution exhibits significant shear thinning behavior. When shaken (high shear), the viscosity drops rapidly, making it easy to pour from the bottle and take; once static (low shear), the viscosity immediately recovers, quickly suspending the particles. This "shake-thin, static-thick" feature is very ideal. Xanthan gum also has shear thinning, but the gel network built by Kari gum sometimes provides a more distinct "gel-sol" transition experience. DETAILED DESCRIPTION

[0024] In order to make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions of the embodiments of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the described embodiments of the present application, all other embodiments obtained by a person of ordinary skill in the art without creative labor fall within the scope of protection of the present application.

[0025] Embodiment 1: A preparation method of an ibuprofen suspension, comprising the following steps:

[0026] a) Disperse 3g of Kari gum and 10g of suspending agent carboxymethylcellulose sodium in part of purified water under heating and stirring conditions, the heating temperature is 75°C, to form an aqueous phase colloid;

[0027] b) Dissolve 20g of sucrose in part of purified water to form a sugar syrup;

[0028] c) Mix the sugar syrup obtained in step b) with the aqueous phase colloid obtained in step a);

[0029] d) Add 40g of ibuprofen to the mixture obtained in step c) and stir to disperse uniformly;

[0030] e) Add a preservative, a flavoring agent, and adjust the pH value of the system to 5.0;

[0031] f) Dilute to 1000 g, homogenize, pressure 40 MPa, cycle 2 times, to obtain the final product.

[0032] Example 2: A preparation method of ibuprofen suspension, comprising the following steps:

[0033] a) Disperse 1 g of Kunming rose gum and 20% suspending agent hydroxypropyl methyl cellulose in part of purified water under heating and stirring conditions, the heating temperature is 70°C, to form an aqueous phase colloid;

[0034] b) Dissolve 4 g of sweetener stevioside in part of purified water to form a sugar syrup;

[0035] c) Mix the sugar syrup obtained in step b) with the aqueous phase colloid obtained in step a);

[0036] d) Add 20 g of ibuprofen to the mixture obtained in step c) and stir to disperse uniformly;

[0037] e) Add preservatives and flavoring agents, and adjust the pH value of the system to 5.5;

[0038] f) Dilute to 1000 g, homogenize, pressure 20 MPa, cycle 3 times, to obtain the final product.

[0039] Example 3: A preparation method of ibuprofen suspension, comprising the following steps:

[0040] a) Disperse 5 g of Kunming rose gum and 5 g of suspending agent sodium alginate in part of purified water under heating and stirring conditions, the heating temperature is 70°C, to form an aqueous phase colloid;

[0041] b) Dissolve 4 g of sweetener protein sugar in part of purified water to form a sugar syrup;

[0042] c) Mix the sugar syrup obtained in step b) with the aqueous phase colloid obtained in step a);

[0043] d) Add 20 g of ibuprofen to the mixture obtained in step c) and stir to disperse uniformly;

[0044] e) Add preservatives and flavoring agents, and adjust the pH value of the system to 4.5;

[0045] f) Dilute to 1000 g, homogenize, pressure 50 MPa, cycle 1 time, to obtain the final product.

[0046] Comparative Example 1: A preparation method of ibuprofen suspension, comprising the following steps:

[0047] a) Disperse 3 g of xanthan gum and 10 g of suspending agent carboxymethyl cellulose sodium in part of purified water under heating and stirring conditions, the heating temperature is 75°C, to form an aqueous phase colloid;

[0048] b) Dissolve 20 g sucrose in partially purified water to form a sugar syrup;

[0049] c) Mix the sugar syrup from step b) with the aqueous colloidal phase from step a);

[0050] d) Add 40 g ibuprofen to the mixture from step c) and stir to disperse evenly;

[0051] e) Add preservatives, flavoring agents, and adjust the pH of the system to 5.0;

[0052] f) Adjust the volume to 1000 g, homogenize at a pressure of 40 MPa for 2 cycles to obtain the final product.

[0053] Comparative Example 2: A method for preparing an ibuprofen suspension, comprising the following steps:

[0054] a) Disperse 3 g of gum karaya, 40 g of ibuprofen, and 10 g of a suspending agent, sodium carboxymethyl cellulose, in partially purified water under heating and stirring conditions, with a heating temperature of 75°C, to form an aqueous colloidal phase;

[0055] b) Dissolve 20 g sucrose in partially purified water to form a sugar syrup;

[0056] c) Mix the sugar syrup from step b) with the aqueous colloidal phase from step a) and stir to disperse evenly;

[0057] d) Add preservatives, flavoring agents, and adjust the pH of the system to 5.0;

[0058] e) Adjust the volume to 1000 g, homogenize at a pressure of 40 MPa for 2 cycles to obtain the final product.

[0059] Comparative Example 3: A method for preparing an ibuprofen suspension, comprising the following steps:

[0060] a) Disperse 3 g of gum karaya, 20 g of sucrose, and 10 g of a suspending agent, sodium carboxymethyl cellulose, in partially purified water under heating and stirring conditions, with a heating temperature of 75°C, to form a mixture;

[0061] b) Add 40 g of ibuprofen to the mixture from step a) and stir to disperse evenly;

[0062] c) Add preservatives, flavoring agents, and adjust the pH of the system to 5.0;

[0063] d) Adjust the volume to 1000 g, homogenize at a pressure of 40 MPa for 2 cycles to obtain the final product.

[0064] Experimental Example 1: Performance Testing

[0065] 1. According to the test method of the settlement volume ratio of oral suspension in the Chinese Pharmacopoeia 2020 edition, the settlement volume ratio and pH value of the ibuprofen suspensions prepared in Examples 1-3 and Comparative Examples are determined, and the determination results are shown in Table 1 below.

[0066] In addition, the above-mentioned settled ibuprofen suspension is rotated at a speed of 20 revolutions / min, and the time required for the settlement to be uniformly dispersed in the system is observed to measure the redispersion of the prepared hydrochloric acid fexofenadine oral suspension, and the results are shown in Table 1 below.

[0067] Table 1 Settlement volume ratio and rotation time of ibuprofen suspension and pH value

[0068]

[0069] According to the detection results in Table 1 above, at 0 month, the ibuprofen suspension prepared in Examples 1-3 of the present application has good suspensibility, Comparative Example 1 does not add casuarina gum, but uses xanthan gum, the suspensibility is reduced, the pH value is increased, and the redispersibility is significantly reduced. With the passage of time, the ibuprofen suspension prepared in Examples 1-3 of the present application still has good suspensibility, while the suspensibility and dispersibility of Comparative Example 1 are significantly reduced, the pH value is increased, which shows that the effect of using casuarina gum as an excipient to prepare ibuprofen suspension is better than using xanthan gum to prepare ibuprofen suspension; Comparative Example 2 and Comparative Example 2 differ in the order of adding excipients, for example, Comparative Example 2 directly mixes casuarina gum, ibuprofen and carboxymethyl cellulose sodium, and Comparative Example 3 first mixes casuarina gum, sucrose and suspending agent carboxymethyl cellulose sodium, and then adds ibuprofen. Due to the high viscosity of the solution, it cannot be dispersed and is in the form of a lump, which causes the ibuprofen to be unable to be uniformly dispersed, the suspensibility and dispersibility are significantly reduced, and the pH value is increased, which shows that the use of casuarina gum to prepare ibuprofen suspension and the process under the specific order of adding excipients has a good effect.

[0070] The embodiments of the present application are given for the purpose of illustration and description, and are not exhaustive or limit the present application to the disclosed form. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiments are selected and described in order to better illustrate the principles and practical application of the present application, and to enable those of ordinary skill in the art to understand the present application so as to design various embodiments with various modifications for specific purposes.

Claims

1. An ibuprofen suspension, characterized in that, Based on the total weight of the suspension, it contains: 2.0-5.0% ibuprofen and 0.1-0.5% erythrina gum.

2. The ibuprofen suspension according to claim 1, characterized in that, It also contains 2-4% sweetener and 0.5-2.0% suspending agent, wherein the suspending agent is selected from one or more of sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and sodium alginate.

3. The ibuprofen suspension according to claim 2, characterized in that, The sweetener is selected from one or more of sucrose, steviol glycosides, and protein sugars.

4. The ibuprofen suspension according to claim 1, characterized in that, The pH value of the suspension is 4.5-5.

5.

5. A method for preparing an ibuprofen suspension as described in any one of claims 1-4, characterized in that, Includes the following steps: a) Disperse the ebony gum and suspending agent in partially purified water under heating and stirring conditions to form an aqueous colloid; b) Dissolve the sweetener in a portion of purified water to form a syrup; c) Mix the syrup obtained in step b) with the aqueous colloid obtained in step a); d) Add ibuprofen to the mixture obtained in step c) and stir to disperse evenly; e) Add preservatives and flavoring agents, and adjust the pH value of the system; f) Adjust the volume, homogenize, and obtain the final product.

6. The method according to claim 5, characterized in that, The heating temperature in step a) is 70-80℃.

7. The method according to claim 5, characterized in that, The homogenization in step f) is carried out using a high-pressure homogenization method with a pressure of 20-50 MPa, and the cycle is repeated 1-3 times.

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