Preparation method of enrofloxacin suspension with high stability and release rate
By using the combination of sodium phenylapropionate, disodium ethylenediaminetetraacetate, Pluronic F68, sodium lactate and other ingredients in the enrofloxacin suspension, multiple protection mechanisms are formed, and the enrofloxacin suspension is solved in a high-temperature environment. The stability issues under this have achieved the improvement of high drug release rate and therapeutic effect.
Patent Information
- Application Number
- CN202411396996.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-09
- Publication Date
- 2025-01-07
AI Technical Summary
Enrofloxacin suspension has stability problems in high temperature environments, especially under cold chain transportation conditions, the drug is easy to decompose, affecting the efficacy of the drug.
By combining sodium phenylapropionate, disodium ethylenediaminetetraacetate, Pluronic F68, sodium lactate, carboxymethylcellulose, glycerol, propylene glycol and enrofloxacin with water, multiple protection mechanisms are formed, the formulation and emulsification process are optimized, and the formulation and emulsification process are improved. Thermal stability and release rate of the drug.
Under 40℃, the drug content is significantly improved, the release rate is accelerated, the treatment effect is significant, the cure rate and efficiency are improved, meeting the drug use needs in high temperature environments.
Smart Images

Figure CN119258017A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of medical technology, and in particular designs a method for preparing an enrofloxacin suspension with high stability and release rate. Background Art
[0002] Enrofloxacin is a fluoroquinolone antibiotic widely used in veterinary clinics. It has a broad-spectrum antibacterial activity, especially against Gram-negative and Gram-positive bacteria. Therefore, it is widely used in the treatment of respiratory, digestive and urinary tract infections in poultry and livestock. Enrofloxacin is usually used in the form of tablets, injections and suspensions for animal medication. Among them, suspension preparations have become a common way of administration in animal husbandry because of their convenience and good palatability.
[0003] However, with global warming and the frequent occurrence of high temperatures, especially in summer and some tropical and subtropical regions, the transportation and storage conditions of drugs are under severe test. The stability of enrofloxacin suspension is highly sensitive to temperature. In a high temperature environment, it is easy to decompose, degrade and other unstable phenomena, which will affect the efficacy of the drug.
[0004] Currently, due to the influence of high temperature weather, cold chain transportation conditions are limited in many areas, especially in remote areas and developing countries, where low-temperature storage and transportation conditions are difficult to guarantee. This places higher demands on the stability of enrofloxacin suspension. Therefore, how to improve the heat stability of enrofloxacin suspension under high temperature conditions to ensure that the drug can maintain its effectiveness and safety for a long time under high temperature conditions, especially under non-cold chain transportation conditions, has become one of the current research focuses in the pharmaceutical field. Summary of the invention
[0005] The object of the present invention is to provide an enrofloxacin suspension having high thermal stability under high temperature environment and a preparation method thereof.
[0006] To achieve the above object, the present invention provides the following technical solutions:
[0007] Firstly, the present invention provides an enrofloxacin suspension with high thermal stability and high drug release rate. The enrofloxacin suspension consists of sodium phenylpropionate, disodium ethylenediaminetetraacetate, Pluronic F68, sodium lactate, carboxymethyl cellulose, glycerol, propylene glycol, enrofloxacin and water.
[0008] Preferably, in terms of mass percentage, the enrofloxacin suspension consists of 1wt% sodium phenylpropionate, 2.5wt% disodium ethylenediaminetetraacetate, 0.5wt% Pluronic F68, 1wt% sodium lactate, 1wt% carboxymethyl cellulose, 10wt% glycerol, 20wt% propylene glycol, 5-10wt% enrofloxacin and 54-59wt% water.
[0009] Preferably, in terms of mass percentage, the enrofloxacin suspension consists of 1wt% sodium phenylpropionate, 2.5wt% disodium ethylenediaminetetraacetate, 0.5wt% Pluronic F68, 1wt% sodium lactate, 1wt% carboxymethyl cellulose, 10wt% glycerol, 20wt% propylene glycol, 5wt% enrofloxacin and 59wt% water.
[0010] Preferably, the high thermal stability is stability in an environment of 40°C.
[0011] Preferably, the enrofloxacin suspension is prepared according to the following preparation method:
[0012] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0013] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 24 wt % of purified water are added and stirred evenly;
[0014] 3) adjusting the pH value to 6.6, placing in a homogenizer, 1000 rpm, emulsifying for 100 min, to obtain an enrofloxacin suspension.
[0015] Secondly, the present invention provides a method for preparing an enrofloxacin suspension with high thermal stability and high drug release rate, the preparation method comprising the following steps:
[0016] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0017] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5-10 wt % of enrofloxacin and 19-24 wt % of purified water are added and stirred evenly;
[0018] 3) After adjusting the pH value, the mixture is placed in a homogenizer for emulsification to obtain an enrofloxacin suspension.
[0019] Preferably, the pH value is adjusted to 6.6;
[0020] The emulsification conditions are 1000 rpm and emulsification time is 100 min.
[0021] Preferably, in step 2), the amount of enrofloxacin added is 5 wt %, and the amount of purified water added is 24 wt %.
[0022] Preferably, the high thermal stability is the stability in an environment of 40°C.
[0023] The beneficial effects of the present invention are:
[0024] 1. The enrofloxacin suspension of the present invention forms multiple protection mechanisms through the reasonable combination of sodium phenylpropionate, disodium ethylenediaminetetraacetate (EDTA-2Na), Pluronic F68, sodium lactate, glycerol and propylene glycol, which significantly improves the stability of the drug in a high temperature environment. Experiments show that at 40°C, the drug content is as high as 96.84%, far exceeding other formulas, proving that the synergistic effect of the combination effectively delays the degradation of the drug.
[0025] 2. The synergistic effect of different ingredients not only improves stability, but also accelerates the release rate of the drug. Experiments show that the cumulative release rate of the enrofloxacin suspension of Example 10 in the first 2 hours is significantly higher than that of other examples, especially in the early release stage (such as the release rate at 1 hour is 60.3%, much higher than 35.2% of Example 1). This shows that the optimized formula can ensure that the drug enters the body quickly and effectively and exerts a therapeutic effect.
[0026] 3. After high temperature treatment, the enrofloxacin suspension can still maintain excellent therapeutic effects. In the E. coli infection experiment, it showed significant therapeutic effects, with a cure rate of up to 80% and an effective rate of 92%. Therefore, this suspension is more suitable for drug use in high temperature environments.
[0027] In conclusion, the present invention enables the enrofloxacin suspension to have better drug stability, release performance and therapeutic effect under high temperature environment through the optimized combination and synergistic effect of the components, thus meeting the needs in practical applications. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 These are pictures of the liver and heart after dissection in the blank control group;
[0029] Figure 2 Pictures of the liver and heart after dissection for the model group;
[0030] Figure 3 This is the picture of the liver and heart after dissection in experimental group a;
[0031] Figure 4 These are pictures of the liver and heart after dissection in experimental group b. DETAILED DESCRIPTION
[0032] The optional embodiments of the present invention will be described in more detail below. Although the optional embodiments of the present invention have been described, it should be understood that the present invention can be implemented in many forms and should not be limited to the specific embodiments described herein.
[0033] Example 1
[0034] 1) Add 1 wt% sodium phenylpropionate to 35 wt% purified water and stir to dissolve;
[0035] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 28 wt % of purified water are added and stirred evenly;
[0036] 3) adjusting the pH value to 6.6, placing in a homogenizer, emulsifying at 1000 rpm for 100 min, to obtain enrofloxacin suspension a.
[0037] Example 2
[0038] 1) adding 1 wt% sodium phenylpropionate and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0039] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 27 wt % of purified water are added and stirred evenly;
[0040] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension b.
[0041] Example 3
[0042] 1) adding 1 wt% sodium phenylpropionate and 2.5 wt% disodium ethylenediaminetetraacetate into 35 wt% purified water and stirring to dissolve;
[0043] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 25.5 wt % of purified water are added and stirred evenly;
[0044] 3) The pH value was adjusted to 6.6, and the mixture was placed in a homogenizer at 1000 rpm for emulsification for 100 min to obtain enrofloxacin suspension c.
[0045] Example 4
[0046] 1) Add 1wt% sodium phenylpropionate and 0.5wt% Pluronic F68 to 35wt% purified water and stir to dissolve;
[0047] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 27.5 wt % of purified water are added and stirred evenly;
[0048] 3) The pH value was adjusted to 6.6, and the mixture was placed in a homogenizer at 1000 rpm for emulsification for 100 min to obtain enrofloxacin suspension d.
[0049] Example 5
[0050] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0051] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 24.5 wt % of purified water are added and stirred evenly;
[0052] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension e.
[0053] Example 6
[0054] 1) adding 1 wt% sodium phenylpropionate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0055] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 26.5 wt % of purified water are added and stirred evenly;
[0056] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension f.
[0057] Example 7
[0058] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate and 0.5 wt% Pluronic F68 to 35 wt% purified water and stirring to dissolve;
[0059] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 25 wt % of purified water are added and stirred evenly;
[0060] 3) The pH value was adjusted to 6.6, and the mixture was placed in a homogenizer at 1000 rpm for emulsification for 100 min to obtain an enrofloxacin suspension.
[0061] Example 8
[0062] 1) adding 1wt% sodium phenylpropionate, 2.5wt% disodium ethylenediaminetetraacetate, 0.5wt% PEG6000 and 1wt% sodium lactate to 35wt% purified water and stirring to dissolve;
[0063] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 24 wt % of purified water are added and stirred evenly;
[0064] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain an enrofloxacin suspension h.
[0065] Example 9
[0066] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0067] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 5 wt % of glycerol, 15 wt % of propylene glycol, 5 wt % of enrofloxacin and 34 wt % of purified water are added and stirred evenly;
[0068] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension i.
[0069] Example 10
[0070] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0071] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 24 wt % of purified water are added and stirred evenly;
[0072] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension j.
[0073] Embodiment 11
[0074] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0075] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 7.5 wt % of enrofloxacin and 21.5 wt % of purified water are added and stirred evenly;
[0076] 3) adjusting the pH value to 6.6, placing in a homogenizer, and emulsifying at 1000 rpm for 100 min to obtain enrofloxacin suspension k.
[0077] Example 12
[0078] 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve;
[0079] 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 10 wt % of enrofloxacin and 19 wt % of purified water are added and stirred evenly;
[0080] 3) adjusting the pH value to 6.6, placing in a homogenizer, 1000 rpm, emulsifying for 100 min, to obtain enrofloxacin suspension 1.
[0081] Experimental testing
[0082] The enrofloxacin suspensions prepared in Examples 1 to 6 were filled with nitrogen, sealed, and placed in a 40° C. incubator for 3 months. Five replicates were set for each example, and then the thermal stability of the enrofloxacin suspension was tested.
[0083] Determined according to the "High Performance Liquid Chromatography Operating Procedure"
[0084] The chromatographic conditions and system suitability test used octadecylsilane bonded silica gel as filler; 0.025 mol / L phosphoric acid solution (adjusted to pH 3.0 with triethylamine)-acetonitrile (83:17) as mobile phase; the detection wavelength was 278 nm. The theoretical plate number calculated based on the enrofloxacin peak should be no less than 1500.
[0085] Determination method: Take an appropriate amount of this product after shaking, weigh accurately, dilute with mobile phase and make a solution containing about 50μg of enrofloxacin per 1ml, shake well, accurately measure 10μl, inject into liquid chromatograph, record chromatogram; take an appropriate amount of enrofloxacin reference substance and determine in the same way. Calculate by peak area according to external standard method, take another product, determine relative density at the same time, convert the amount of test sample into milliliters, calculate, and get.
[0086] Table 1 Differences in thermal stability of enrofloxacin suspensions under high temperature conditions
[0087]
[0088]
[0089] Example 1: Only 1wt% sodium phenylpropionate was used as an antioxidant, and no other chelating agents, sodium lactate or surfactants were added to the basic formula. The drug content after two months was 53.24%, which was significantly lower than that of other examples, indicating that the basic formula could not provide sufficient stability, the antioxidant effect of sodium phenylpropionate alone was limited, and the drug was easily degraded.
[0090] Example 2: Based on Example 1, 1 wt% sodium lactate was added to significantly improve the pH buffering capacity of the formula, ensuring the relative stability of the pH value of the solution at high temperature. The enrofloxacin content was increased to 62.47%, indicating that the combination of sodium lactate and sodium phenylpropionate has a certain synergistic effect and delays the degradation of the drug.
[0091] Example 3: 2.5 wt% of disodium ethylenediaminetetraacetate (EDTA-2Na) was added to Example 1 to enhance the chelation effect and significantly reduce the oxidative degradation caused by metal ions. The results showed that the drug content increased to 67.16%, indicating that EDTA-2Na and sodium phenylpropionate acted together to synergistically delay the oxidative degradation of the drug.
[0092] Example 4: Based on Example 1, 0.5 wt% Pluronic F68 was added as a surfactant to enhance the stability of the suspension, and the drug content reached 64.27%. Pluronic F68 improved the dispersibility of the drug in the solution and prevented aggregation and sedimentation problems under high temperature conditions.
[0093] Example 5: Although EDTA-2Na and sodium lactate provide good chelation and pH buffering effects in Example 5, and the drug content is significantly increased, the drug stability is still insufficient without the use of Pluronic F68. In Example 10, Pluronic F68 works synergistically with other ingredients to further enhance the thermal stability of the drug.
[0094] Example 6: Example 6 lacks EDTA-2Na as a chelating agent, resulting in a drug content significantly lower than that of Example 10. In the absence of a chelating agent, the degradation rate of the drug is accelerated in a high temperature environment.
[0095] Example 7: Although Example 7 combines EDTA-2Na and Pluronic F68 to provide good chelation and surface activity, the lack of pH buffering effect of sodium lactate causes a certain degree of degradation of the drug under high temperature environment. Sodium lactate can effectively maintain the acid-base balance of the solution and prevent degradation caused by pH fluctuations. The synergistic effect of sodium lactate, EDTA-2Na and Pluronic F68 in Example 10 allows the drug to be fully protected in terms of chemical and physical stability, and the drug content is significantly higher than that in Example 7.
[0096] Example 8: In Example 8, PEG6000 was used to replace Pluronic F68. Although PEG6000 as a surfactant can improve the physical stability of the drug, it cannot exert the synergistic effect with sodium phenylpropionate, EDTA-2Na and sodium lactate like Pluronic F68 under high temperature environment.
[0097] The formulation of Example 9 is similar to that of Example 10, but the ratio of glycerol to propylene glycol in the solution is different. Example 10 further optimizes the rheology of the suspension and the dispersibility of the drug particles by fine-tuning the ratio of these solvents, thereby reducing the sedimentation problem.
[0098] In general, the combination of sodium phenylpropionate, EDTA-2Na, sodium lactate, and Pluronic F68 showed significant synergistic effects in terms of chemical stability and physical stability. EDTA-2Na chelates metal ions to reduce oxidative degradation, sodium lactate maintains pH stability, Pluronic F68 improves the dispersibility of the suspension, and sodium phenylpropionate acts as an antioxidant to provide basic protection. Compared with Examples 5-9, the components of Example 10 form a high degree of synergy at the optimal ratio, ultimately ensuring the optimal thermal stability of enrofloxacin under high temperature conditions.
[0099] Experimental test 2
[0100] In order to detect whether enrofloxacin can be used normally for treatment after high temperature storage, the present invention selects enrofloxacin in Example 1 and Example 10 to test the cumulative release rate:
[0101] Experimental steps:
[0102] First, prepare the release medium: take 16.4 ml of dilute hydrochloric acid (equivalent to 3.84 ml of hydrochloric acid), add about 8000 ml of water and 10 g of pepsin, shake well, and dilute with water to 1000 ml to obtain simulated gastric fluid. Place the suspension (equivalent to 200 mg of enrofloxacin raw material) in a dialysis tube, and then place the dialysis tube in a container containing the release medium to release the drug;
[0103] The dialysis device was placed in a thermostatic oscillator and the drug release experiment was performed at a set temperature of 37°C ± 0.5°C and a rotation speed of 100 rpm;
[0104] At specific time points (5 min, 10 min, 20 min, 30 min, 60 min), 5 ml of sample was taken and supplemented with release medium of the same volume, temperature, and pH value to keep the volume of release medium constant;
[0105] The samples were centrifuged to separate the solid particles and the released drugs in the suspension, and the drug concentration in the supernatant was determined using high performance liquid chromatography (HPLC).
[0106] Experimental results:
[0107] The experimental results are shown in Table 2:
[0108] Table 2 Release rate of enrofloxacin suspension of Example 1 and Example 10 at different times
[0109]
[0110] It can be seen from the results that the release rate of the enrofloxacin suspension of Example 10 is significantly faster than that of the enrofloxacin suspension of Example 1, especially within the first 5 minutes, the cumulative release rate of the enrofloxacin suspension of Example 10 is significantly higher than that of Example 1. This indicates that the enrofloxacin suspension of Example 10 still has an excellent release rate after high temperature treatment.
[0111] Experimental test 3
[0112] This example tests the therapeutic effect of high temperature treated enrofloxacin on Escherichia coli infection
[0113] Experimental steps:
[0114] Randomly select 100 chicks of similar weight (not immunized with E. coli vaccine, raised normally before the experiment, fed with self-prepared complete powder feed without any drugs, and allowed to eat and drink freely);
[0115] When the rats were raised to 15 days old, they were randomly divided into 4 groups, each with 25 rats, including a blank control group (normal feeding without treatment), a model group (only inoculated with Escherichia coli without drug treatment), an experimental group a (inoculated with Escherichia coli and administered with the enrofloxacin suspension treated with high temperature in Example 1), and an experimental group b (inoculated with Escherichia coli and administered with the enrofloxacin suspension treated with high temperature in Example 10);
[0116] Referring to the above grouping, 0.15 mL of Escherichia coli solution (standard strain of Escherichia coli, serotype O78) was inoculated into the breast muscle of chickens for every 100 g of body weight;
[0117] When the chickens show the main symptoms: lethargy, head retraction and closed eyes, increased water intake, reduced food intake, and green-white loose feces, drug treatment is carried out: add 1 ml of enrofloxacin suspension to every 1L of drinking water, and administer the drug twice a day in the morning and evening in drinking water for 5 consecutive days, and calculate the mortality rate, cure rate and effectiveness rate.
[0118] Cure rate: During the test period, chickens were considered cured if their mental state, appetite, etc. returned to normal after administration.
[0119] Mortality rate: During the trial, typical symptoms of Escherichia coli disease appeared and death occurred. Autopsy of the body showed typical pathological features in the heart and liver, and it was determined that the death was caused by infection with Escherichia coli disease.
[0120] Effectiveness: After medication, both the chickens that were cured and the chickens that did not die but showed clinical symptoms were considered “effective”; that is, the ratio of the number of surviving chickens in each group to the number of experimental chickens at the end of the trial was the effective rate.
[0121] The anatomical diagrams of the blank control group, model group, experimental group a and experimental group b are shown in Figure 1-4 As shown, the heart and liver of the blank control group were completely normal, while the heart and liver of the model group had obvious lesions, indicating that the infection of the present invention was successful, and the hearts and livers of the cured chickens in experimental group a and experimental group b returned to normal.
[0122] Table 3 Differences in therapeutic effects among different experimental treatment groups
[0123]
[0124] As can be seen from Table 3, although the cure rate and effective rate of the experimental group a fed with enrofloxacin prepared in Example 1 were higher than those of the model group, the overall effect was poor;
[0125] The cure rate and the effective rate of the experimental group b fed with the enrofloxacin suspension prepared in Example 10 were significantly improved compared with those of the experimental group a, especially whether the effective rate was significantly improved, indicating that the enrofloxacin suspension prepared in Example 10 of the present invention still has an excellent therapeutic effect after being placed in a high temperature environment, and can meet the needs of actual infection treatment.
Claims
1. An enrofloxacin suspension with high thermal stability and high drug release rate, characterized in that: The enrofloxacin suspension consists of sodium phenylpropionate, disodium ethylenediaminetetraacetate, Pluronic F68, sodium lactate, carboxymethyl cellulose, glycerol, propylene glycol, enrofloxacin and water.
2. The enrofloxacin suspension according to claim 1, characterized in that According to mass percentage, the enrofloxacin suspension consists of 1wt% sodium phenylpropionate, 2.5wt% disodium ethylenediaminetetraacetate, 0.5wt% Pluronic F68, 1wt% sodium lactate, 1wt% carboxymethyl cellulose, 10wt% glycerol, 20wt% propylene glycol, 5-10wt% enrofloxacin and 54-59wt% water.
3. The enrofloxacin suspension according to claim 2, characterized in that According to mass percentage, the enrofloxacin suspension consists of 1wt% sodium phenylpropionate, 2.5wt% disodium ethylenediaminetetraacetate, 0.5wt% Pluronic F68, 1wt% sodium lactate, 1wt% carboxymethyl cellulose, 10wt% glycerol, 20wt% propylene glycol, 5wt% enrofloxacin and 59wt% water.
4. The enrofloxacin suspension according to claim 3, characterized in that The high thermal stability refers to the stability in an environment of 40°C.
5. The enrofloxacin suspension according to claim 4, characterized in that The enrofloxacin suspension is prepared according to the following preparation method: 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve; 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5 wt % of enrofloxacin and 24 wt % of purified water are added and stirred evenly; 3) adjusting the pH value to 6.6, placing in a homogenizer, 1000 rpm, emulsifying for 100 min, to obtain an enrofloxacin suspension.
6. A method for preparing an enrofloxacin suspension with high thermal stability and high drug release rate, characterized in that: The preparation method comprises the following steps: 1) adding 1 wt% sodium phenylpropionate, 2.5 wt% disodium ethylenediaminetetraacetate, 0.5 wt% Pluronic F68 and 1 wt% sodium lactate to 35 wt% purified water and stirring to dissolve; 2) After 1 wt % of carboxymethyl cellulose is dissolved by stirring, 10 wt % of glycerol, 20 wt % of propylene glycol, 5-10 wt % of enrofloxacin and 19-24 wt % of purified water are added and stirred evenly; 3) After adjusting the pH value, the mixture is placed in a homogenizer for emulsification to obtain an enrofloxacin suspension.
7. The preparation method according to claim 6, characterized in that: The pH value is adjusted to 6.6; The emulsification conditions are 1000 rpm and emulsification time is 100 min.
8. The preparation method according to claim 7, characterized in that: In the step 2), the amount of enrofloxacin added is 5 wt %, and the amount of purified water added is 24 wt %.
9. The preparation method according to claim 8, characterized in that: High thermal stability refers to the stability in an environment of 40°C.