Suspension particle size detection method

Abstract

The invention relates to the technical field of pharmacy, and discloses a suspension particle size detection method, which comprises the following steps: preparing a dispersion medium: mixing 2.0-3.0 g of polysorbate 80 and 4500-5500 ml of water, and stirring to form a uniform mixed solution; ibuprofen is added into the dispersion medium to form a saturated aqueous solution; the preparation method comprises the following steps: taking an ibuprofen suspension drop, adding 1-3ml of a high-concentration pigment aqueous solution for dyeing, centrifuging, taking an upper-layer ibuprofen raw material medicine, abandoning a dyed auxiliary material solution, and putting into a beaker; according to the method disclosed by the invention, the inactive ingredients are effectively removed from the suspension by utilizing a reverse dyeing technology and a centrifugal separation step, and the purity of the ibuprofen raw material medicine is remarkably improved. By removing potential interference components, the accuracy of measured data and the reliability of analysis are ensured, and meanwhile, by strictly controlling the power, the frequency, the processing time and the stirring speed of ultrasonic waves, the aggregation of particles is greatly reduced, and the consistency and the repeatability of measurement results are ensured.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, in particular to a method for detecting suspension particle size. Background Art

[0002] In modern industry and scientific research, the particle size in the suspension directly affects the quality and performance of its products. Especially in the pharmaceutical industry, the size and distribution of the particle size have a significant impact on the release rate, absorption efficiency and stability of the drug. Therefore, developing a reliable and accurate particle size determination method is the key to improving product quality. However, existing particle size determination technologies face several major problems:

[0003] Particle dispersion problem: In many traditional particle size determination methods, such as dynamic light scattering (DLS) or laser diffraction, the sample must be highly uniformly dispersed before measurement. Insufficient dispersion will cause particle aggregation, which will affect the accuracy and repeatability of the measurement results.

[0004] Complexity of sample pretreatment: To prevent particle aggregation, traditional methods often require the use of chemical dispersants or long-term physical stirring. These pretreatment steps are not only cumbersome, but some chemical dispersants may also affect the surface properties of the particles, thereby indirectly affecting the measurement results.

[0005] Interference from inactive ingredients: In complex suspensions, inactive ingredients such as stabilizers or suspending agents may have a particle size similar to that of the active ingredients. Traditional measurement techniques have difficulty distinguishing these ingredients, which complicates data interpretation and affects the accuracy of the results.

[0006] Therefore, the present invention proposes a suspension particle size detection method to solve the deficiencies of the prior art. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention provides a method for detecting the particle size of a suspension. The present invention significantly improves the separation efficiency of inactive ingredients and active ingredients by using reverse staining technology, and optimizes the dispersibility of particles by combining ultrasonic treatment and mechanical stirring technology, thereby simplifying the sample pretreatment process. The comprehensive application of these technologies not only improves the accuracy of the measurement, but also improves the simplicity of operation and the reliability of the measurement, so that the present invention has significant application prospects and practical value in related fields.

[0008] To achieve the above objectives, the present invention is implemented by the following technical scheme: A method for detecting the particle size of a suspension comprises the following steps:

[0009] a. a saturated aqueous solution of ibuprofen, comprising mixing 2.0 to 3.0 g of polysorbate 80 with 4500 to 5500 ml of water and stirring to form a uniform mixture; adding 5 g of ibuprofen thereto and stirring for 60 minutes to form a saturated aqueous solution;

[0010] b. Prepare a dispersion medium and filter the saturated aqueous solution of ibuprofen using a filter membrane with a pore size of 0.45 μm to remove incompletely dissolved particles.

[0011] c. Take ibuprofen suspension drops, add 1-3 ml of high concentration pigment aqueous solution for dyeing, centrifuge, take the upper ibuprofen API, and discard the dyed excipient solution, and place in a beaker;

[0012] d. Then 150-200 ml of the dispersion medium is added to a beaker and treated by ultrasonic treatment and mechanical stirring to disperse the active ingredient particles in the suspension in the dispersion medium;

[0013] e. Use a laser particle size analyzer to measure the particle size of the treated samples.

[0014] Preferably, the refractive index of the dispersion medium is set between 1.30 and 1.35, and the refractive index of the active ingredient particles is set between 1.40 and 1.45.

[0015] Preferably, the speed adjustment range of the mechanical stirring device is 200 to 700 revolutions per minute, the power adjustment range of the ultrasonic treatment device is 250 to 550 watts, the frequency is set to 35 to 45 kHz, and the ultrasonic treatment time is 120 to 200 seconds.

[0016] Preferably, the refractive index of the dispersion medium is 1.33, and the refractive index of the ibuprofen particles in the suspension is 1.436.

[0017] Preferably, the saturated aqueous solution of ibuprofen is filtered using a filter membrane with a pore size of 0.45 micrometers to remove incompletely dissolved particles.

[0018] Preferably, the method comprises dyeing the inactive ingredients in the suspension with a pigment aqueous solution, and then separating the dyed inactive ingredients from the ibuprofen bulk drug by centrifugation.

[0019] Preferably, the method further comprises a step of manual stirring immediately after the stirring and ultrasonic treatment are completed to ensure uniform distribution of the active ingredient particles in the dispersion medium, thereby increasing the measurement accuracy.

[0020] Preferably, the amount of dispersion medium added during the ultrasonic treatment and mechanical stirring is 150 to 200 ml, so as to keep the particle size distribution of the raw material drug separated from the suspension uniform after treatment.

[0021] Preferably, the particle size determination step further comprises:

[0022] e1. Turn on the instrument according to the operating procedures of the laser particle size analyzer and stabilize it for 20-40 minutes, with the particle absorption rate set to 0.1;

[0023] e2. Adjust the pump speed to 1800-2200 rpm;

[0024] e3. Add 450-550 mL of dispersion medium to the EV beaker;

[0025] e4. Add the sample until the turbidity is within the shading range of 8%-20%;

[0026] e5. After the shading degree stabilizes, measure it within one minute, repeat the measurement twice and take the average value as the final measurement result.

[0027] The present invention provides a method for detecting the particle size of a suspension, which has the following beneficial effects:

[0028] 1. The present invention utilizes reverse staining technology and centrifugation separation steps to effectively remove inactive ingredients from the suspension, which significantly improves the purity of the ibuprofen API. By removing potential interfering components, the accuracy of the measurement data and the reliability of the analysis are ensured.

[0029] 2. The present invention combines ultrasonic treatment and mechanical stirring technology to achieve uniform and efficient dispersion of active ingredient particles in the suspension. By strictly controlling the power, frequency, treatment time and stirring speed of the ultrasonic wave, the aggregation of particles is greatly reduced, ensuring the consistency and repeatability of the measurement results.

[0030] 3. The present invention uses manual stirring to further ensure the uniform distribution of active ingredient particles in the dispersion medium and the representativeness of the sample. Manual stirring increases the flexibility of the processing process. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a flow chart of the suspension particle size detection method. DETAILED DESCRIPTION

[0032] The following will be combined with the drawings in the specification of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Example:

[0034] Please refer to the attached Figure 1 :

[0035] Example 1: Basic suspension particle size detection method

[0036] Step content:

[0037] Preparation of dispersion medium: 2.5 g of polysorbate 80 was mixed with 5000 ml of water and stirred for 5 minutes to form a uniform mixture. 5 g of ibuprofen was added to the mixture and stirred for 60 minutes to form a saturated aqueous solution of ibuprofen.

[0038] The ibuprofen saturated aqueous solution was filtered using a filter membrane with a pore size of 0.45 micrometers to remove incompletely dissolved particles, and the obtained ibuprofen saturated aqueous solution was used as a dispersion medium.

[0039] Take ibuprofen suspension drops, add 2 ml of high-concentration pigment aqueous solution for dyeing, centrifuge, take the upper layer of ibuprofen raw material, and discard the dyed auxiliary material solution.

[0040] The collected ibuprofen bulk drug was placed in a beaker, 175 ml of dispersion medium was added, and ultrasonic treatment (power 350 watts, frequency 40 kHz, treatment time 160 seconds) and mechanical stirring (rotation speed 500 rpm) were performed.

[0041] After the treatment, the particle size was measured using a laser particle size analyzer.

[0042] Summary of Examples: This example provides a basic suspension particle size detection method that combines chemical and physical processing steps to ensure uniform distribution and accurate measurement of the active ingredient.

[0043] Example 2: Enhanced dispersion effect

[0044] Step content:

[0045] The dispersion medium was prepared according to the steps of Example 1.

[0046] Ultrasonic treatment.

[0047] Ultrasonic treatment was performed at maximum power (550 watts) and duration (200 seconds), and mechanical stirring was adjusted to 700 rpm.

[0048] The particle size was measured using a laser particle size analyzer.

[0049] Summary of the embodiment: This embodiment effectively disperses the aggregated particles by strengthening the ultrasonic treatment, improves the dispersion, and enhances the consistency and repeatability of the measurement.

[0050] Example 3: Finely controlled suspension processing

[0051] Step content:

[0052] The dispersion medium was prepared and dyed as described in Example 1.

[0053] After centrifugation, 150 ml of dispersion medium was used to disperse the ibuprofen bulk drug obtained by centrifugation.

[0054] The pump speed was adjusted to 2100 rpm during ultrasonic and mechanical agitation to optimize the treatment effect.

[0055] Perform particle size measurement.

[0056] Summary of the Example: By finely controlling the pump speed and turbidity, this example ensures the optimal state of the suspension before measurement, thereby improving the accuracy of particle size measurement.

[0057] Example 4: Efficient processing of complex suspensions

[0058] Step content:

[0059] The dispersion medium and ibuprofen suspension were prepared according to the procedure of Example 1.

[0060] Staining and centrifugation were performed before sonication.

[0061] The separated ibuprofen API was re-processed with 200 mL of dispersion medium and manually stirred to ensure uniform distribution.

[0062] The pump speed was adjusted to 1800 rpm and two measurements were taken to determine the particle size.

[0063] Summary of Examples: This example uses a comprehensive chemical and physical method to ensure the uniformity and accurate measurement of the suspension by manual stirring and precise adjustment of the pump speed.

[0064] Example 5: Optimization of pigment dyeing and separation efficiency

[0065] Step content:

[0066] Prepare a dispersion medium and add ibuprofen according to the procedure of Example 1.

[0067] After adding a high concentration of pigment aqueous solution, centrifugation is performed to separate the inactive components of the dye.

[0068] Undyed ibuprofen bulk drug substance was collected, dispersed using 200 ml of dispersion medium, and treated with ultrasonic and mechanical stirring.

[0069] The particle size was measured using a laser particle size analyzer.

[0070] Summary of the embodiment: By optimizing the pigment dyeing and centrifugal separation steps, this embodiment effectively improves the purity of the ibuprofen API, reduces the measurement error, and improves the efficiency and accuracy of the entire particle size detection process.

[0071] Summary

[0072] These five examples demonstrate the diversity and flexibility of the present invention, from basic suspension processing to the combination of complex chemical and physical processing techniques. Each example has its own characteristics, providing the best solution in different scenarios, ensuring high-precision and high-repeatability particle size measurement results, and demonstrating the wide applicability and practical value of the present invention in the field of suspension particle size detection.

[0073] Comparative experiment:

[0074] Experiment 1: Comparison of reverse staining and centrifugation efficiency

[0075] Comparison of technical solutions:

[0076] Prior art: Generally, whole sample staining is used without specific differentiation between active and inactive ingredients, followed by separation attempts by simple physical methods such as low-speed centrifugation or gravity sedimentation, which is inefficient and often results in the loss of active ingredients.

[0077] The technical solution of the present invention is to specifically use the reverse staining technology to stain only the inactive ingredients, and then use high-speed centrifugation (3000 revolutions, 5 minutes) to effectively separate the stained inactive ingredients from the unstained active ingredients.

[0078] Experimental setup:

[0079] Sample: Suspension containing ibuprofen and various inactive suspending agents.

[0080] Colorants: Highly selective colorants for inactive ingredients.

[0081] Centrifugation: 3000 rpm, 5 min.

[0082] Data recording: The purity and size of the particles were recorded by high performance liquid chromatography (HPLC) and particle size analyzer.

[0083] Experimental data table:

[0084]

[0085] Experiment 2: Comparison of the efficiency of ultrasonic treatment and mechanical stirring

[0086] Comparison of technical solutions:

[0087] Existing technology: Usually only mechanical stirring or single ultrasonic treatment is used, and the two methods are not combined. This limits the uniform dispersion of particles, especially in highly concentrated or viscous suspensions.

[0088] The technical solution of the present invention is to combine ultrasonic treatment and mechanical stirring to synergistically enhance the particle dispersion effect. Ultrasonic treatment uses medium to high power and moderate frequency, and mechanical stirring uses optimized speed and time to achieve optimal dispersion.

[0089] Experimental setup:

[0090] Sample: Ibuprofen suspension.

[0091] Ultrasonic settings: power 450 W, frequency 40 kHz, treatment time 150 s.

[0092] Stirring speed: 500rpm.

[0093] Experimental data table:

[0094]

[0095] Experiment 3: Comparison of the effects of manual stirring and filtering steps

[0096] Comparison of technical solutions:

[0097] Prior art: Conventional operations may ignore the delicate manual stirring step and directly use basic mechanical stirring before testing, which may result in uneven particle distribution.

[0098] The technical solution of the present invention is to introduce a manual stirring step, thereby ensuring that particles of all sizes are used for the final measurement, which significantly improves the accuracy and representativeness of the measurement.

[0099] Experimental setup:

[0100] Sample: Ibuprofen suspension.

[0101] Experimental data table:

[0102]

[0103] These detailed comparative experiments demonstrate that the present invention significantly optimizes the process of measuring particles in suspension by precisely controlling the processing parameters and introducing new pre- and post-processing steps.

[0104] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for detecting suspension particle size, characterized in that: The following steps are involved: a. a saturated aqueous solution of ibuprofen, comprising mixing 2.0 to 3.0 g of polysorbate 80 with 4500 to 5500 ml of water and stirring to form a uniform mixture; adding 5 g of ibuprofen thereto and stirring for 60 minutes to form a saturated aqueous solution; b. Prepare a dispersion medium and filter the saturated aqueous solution of ibuprofen using a filter membrane with a pore size of 0.45 μm to remove incompletely dissolved particles. c. Take ibuprofen suspension drops, add 1-3 ml of high concentration pigment aqueous solution for dyeing, centrifuge, take the upper ibuprofen API, and discard the dyed excipient solution, and place in a beaker; d. Then 150-200 ml of the dispersion medium is added to a beaker and treated by ultrasonic treatment and mechanical stirring to disperse the active ingredient particles in the suspension in the dispersion medium; e. Use a laser particle size analyzer to measure the particle size of the treated samples.

2. A suspension particle size detection method according to claim 1, characterized in that, The refractive index of the dispersion medium is set between 1.30 and 1.35, and the refractive index of the active ingredient particles is set between 1.40 and 1.

45.

3. A suspension particle size detection method according to claim 1, characterized in that, The speed adjustment range of the mechanical stirring device is 200 to 700 revolutions per minute, the power adjustment range of the ultrasonic treatment device is 250 to 550 watts, the frequency is set to 35 to 45 kilohertz, and the ultrasonic treatment time is 120 to 200 seconds.

4. A suspension particle size detection method according to claim 1, characterized in that, The refractive index of the dispersion medium is 1.33, and the refractive index of the ibuprofen particles in the suspension is 1.

436.

5. A suspension particle size detection method according to claim 1, characterized in that: After the stirring and ultrasonic treatment, the ibuprofen saturated aqueous solution was filtered using a filter membrane with a pore size of 0.45 micrometers to remove incompletely dissolved particles.

6. A suspension particle size detection method according to claim 1, characterized in that: The method comprises dyeing the inactive ingredients in the suspension with an aqueous solution of a pigment and then separating the dyed inactive ingredients from the ibuprofen API by centrifugation.

7. A suspension particle size detection method according to claim 1, characterized in that: The method further includes a step of manual stirring immediately after the stirring and ultrasonic treatment is completed to ensure uniform distribution of active ingredient particles in the dispersion medium, thereby increasing measurement accuracy.

8. A suspension particle size detection method according to claim 1, characterized in that: The amount of dispersion medium added during the ultrasonic treatment and mechanical stirring process is 150 to 200 ml to keep the particle size distribution of the raw material drug separated from the suspension uniform after treatment.

9. A suspension particle size detection method according to claim 1, characterized in that: The particle size determination step further comprises: e1. Turn on the instrument according to the operating procedures of the laser particle size analyzer and stabilize it for 20-40 minutes, with the particle absorption rate set to 0.1; e2. Adjust the pump speed to 1800-2200 rpm; e3. Add 450-550 mL of dispersion medium to the EV beaker; e4. Add the sample until the turbidity is within the shading range of 8%-20%; e5. After the shading degree stabilizes, measure it within one minute, repeat the measurement twice and take the average value as the final measurement result.

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