A high-throughput nanosuspension co-crystal preparation device based on acoustic resonance

Abstract

The utility model provides a kind of high-throughput nanometer suspension agent eutectic preparation equipment based on acoustic resonance, mainly relates to drug nanocrystallization and eutectic preparation technical field.A kind of high-throughput nanometer suspension agent eutectic preparation equipment based on acoustic resonance, including mixing container, sealing cover, acoustic resonance system, the sealing cover shape is compatible with mixing container, several recessed holes are opened in the mixing container, several convex columns are equipped on the sealing cover, the convex column lateral wall is equipped with annular sealing ring, the acoustic resonance system includes resonance platform and fixing device, supporting device, the resonance platform includes vibration table surface, drive machine, the drive machine is fixedly arranged at resonance table surface bottom.The utility model has the beneficial effect that: the equipment composition is simple, low in cost, can realize the preparation of single batch multiple groups of drug nanometer suspension agent or eutectic, is conducive to the efficient screening of nanometer suspension agent stabilizer and eutectic formation.

Description

Technical Field

[0001] This utility model mainly relates to the field of drug nano-suspension and co-crystal preparation technology, specifically a high-throughput nano-suspension co-crystal preparation device based on acoustic resonance. Background Technology

[0002] With the increasing proportion of poorly soluble drugs in the pharmaceutical field (approximately 40% of candidate drugs have solubility defects), nanocrystal technology and drug co-crystal development have become core strategies for improving bioavailability. The screening of stabilizers for nanosuspensions is mainly based on trial and error, a complex process involving multivariate optimization that requires systematic experimental design.

[0003] However, most existing commercial high-shear wet mills and high-pressure homogenizers only support single-batch operation, resulting in low efficiency (only supporting single-batch operation) and uneven particle size between batches. On the other hand, traditional eutectic preparation methods (such as solvent evaporation and grinding) suffer from low efficiency, poor batch repeatability, and difficulty in high-throughput screening. While mechanochemical methods (such as ball milling) can achieve solvent-free eutectic preparation, they suffer from high energy consumption and localized overheating leading to drug degradation. In existing technologies, sonochemical methods (such as ultrasound-assisted methods) can be used for eutectic preparation, but traditional ultrasonic equipment cannot perform multiple parallel experiments, and high-frequency ultrasound can easily cause molecular structure damage. Furthermore, conventional acoustic resonance equipment uses metal or polymer containers, which are prone to energy loss due to material resonance damping, and long-term use can lead to wear and contamination of drugs. Therefore, there is an urgent need to develop a high-throughput, high-efficiency nanosuspension and eutectic preparation device to overcome the low-throughput and material compatibility bottlenecks of traditional technologies. Utility Model Content

[0004] To address the shortcomings of existing technologies, this invention provides a high-throughput nano-suspension eutectic preparation device based on acoustic resonance, which mainly solves the problems of low efficiency, high energy consumption, and easy sample contamination in existing technologies.

[0005] To achieve the above objectives, this utility model employs the following technical solution:

[0006] A high-throughput nano-suspension eutectic preparation device based on acoustic resonance includes a mixing container, a sealing cap, and an acoustic resonance system. The sealing cap is shaped to fit the mixing container, and the mixing container has several recessed holes. The sealing cap has several protruding posts, and the sidewalls of the protruding posts are provided with annular sealing rings. The acoustic resonance system includes a resonance platform, a fixing device, and a support device. The resonance platform includes a vibration table and a drive motor. The drive motor is fixedly installed at the bottom of the resonance table. The mixing container, the sealing cap, and the resonance platform are fixedly installed together by the fixing device. The fixing device includes a square saddle clip, in which the mixing container and the sealing cap are installed. A square clamp is installed on the outer side of the square saddle clip and the side end of the vibration table. Screws are installed on the upper and lower sides of the square clamp.

[0007] Several of the aforementioned protruding posts are adapted to the concave holes.

[0008] The annular sealing ring can be made of either polytetrafluoroethylene or medical-grade silicone.

[0009] The mixing container has concave holes arranged in an array, with a diameter of 10-20 mm, a depth of 0.75-15 mm, and a hole spacing of ≥1.0 times the hole diameter.

[0010] The support device includes a base, on which a vibration spring is fixedly installed, and the bottom of the vibration table is fixedly connected to the vibration spring.

[0011] Rotate the screw to press the end of the square saddle clip together with the side end of the vibration table.

[0012] Compared with the existing technology, the beneficial effects of this utility model are:

[0013] High-throughput processing: ≥60 different formulations can be screened simultaneously in a single batch, resulting in a significant improvement in efficiency;

[0014] Energy-saving and environmentally friendly: Low-frequency sound wave energy consumption is reduced by more than 40%;

[0015] Quality controllable: Zirconia containers ensure efficient energy transfer and good product uniformity;

[0016] Multifunctionality: Suitable for a variety of poorly soluble drugs (ibuprofen, griseofulvin, etc.) and eutectic formations (saccharin, caffeic acid, etc.). Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the overall structure of this utility model;

[0018] Figure 2 This is a top view and a front perspective structural schematic diagram of the mixing container of this utility model;

[0019] Figure 3This is a top view and a front view structural schematic diagram of the sealing cover of this utility model.

[0020] The following are the labels in the attached diagram: 1. Base; 2. Vibration spring; 3. Vibration table; 4. Mixing container; 5. Sealing cover; 6. Drive motor; 7. Square saddle clip; 8. Screw; 9. Square clamp; 40. Concave hole; 50. Protruding post. Detailed Implementation

[0021] The present invention will be further described in conjunction with the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent forms also fall within the scope defined in this application.

[0022] Combined with appendix Figures 1-3 A high-throughput nano-suspension eutectic preparation device based on acoustic resonance includes a mixing container 4, a sealing cover 5, and an acoustic resonance system. The sealing cover 5 is shaped to fit the mixing container 4. The mixing container 4 has several recessed holes 40. The sealing cover 5 has several protruding posts 50. The sidewalls of the protruding posts 50 are provided with annular sealing rings. The acoustic resonance system includes a resonance platform, a fixing device, and a support device. The resonance platform includes a vibration table 3 and a drive motor 6. The drive motor 6 is fixedly installed at the bottom of the resonance table 3. The mixing container 4, the sealing cover 5, and the resonance platform are fixedly installed together by the fixing device. The fixing device includes a square saddle clip 7. The mixing container 4 and the sealing cover 5 are installed in the square saddle clip 7. A square clamp 9 is installed on the outer side of the end of the square saddle clip 7 and the side end of the vibration table 3. Screws 8 are installed on the upper and lower sides of the square clamp 9.

[0023] Several of the protruding posts 50 are adapted to the concave holes 40.

[0024] The annular sealing ring can be made of either polytetrafluoroethylene or medical-grade silicone.

[0025] The mixing container 4 has concave holes 40 arranged in an array with a diameter of 10-20 mm, a depth of 0.75-15 mm, and a hole spacing of ≥1.0 times the hole diameter, so as to realize high-throughput parallel experiments.

[0026] The support device includes a base 1, on which a vibration spring 2 is fixedly installed, and the bottom of the vibration table 3 is fixedly connected to the vibration spring 2.

[0027] Rotate the screw 8 to press the end of the square saddle clip 7 against the side end of the vibration table surface 3.

[0028] The mixing container 4 is a single-sided sealed zirconia ceramic plate. The recess 40 of the mixing container 4 is used to load the drug and grinding media. The isolation design of the recess 40 prevents cross-contamination. The sealing cover 5 is a zirconia ceramic plate with a protrusion 50 that matches the recess 40. The sealing cover 5 and the mixing container 4 are mechanically pressed together. The protrusion 50 is inserted into the recess 40 to form an independent sealed reaction chamber, which enhances energy conduction. The pressure in the independent sealed reaction chamber is adjustable from 0.1 to 5 MPa to ensure efficient sound wave transmission and prevent material leakage.

[0029] The acoustic resonance system is a customized simple resonance platform that outputs low-frequency (5-50 Hz) and high-acceleration (10-150 m / s²) vertical acoustic waves, which are coupled to the mixing container 4 via a fixing device to excite the high-frequency shear motion of the grinding media and the drug in the concave hole 40, driving the drug nano-sizing or co-crystallization.

[0030] The drive unit 6 is an electromagnetic vibrator with a selectable frequency range of 0-50 Hz and an adjustable acceleration range of 10-120 m / s², to adapt to the mechanical properties of different drugs or eutectic precursors.

[0031] The grinding media are zirconia or ceramic microspheres with a particle size of 0.3-3 mm and a filling rate of 30-70% of the pore volume to optimize shearing efficiency and avoid excessive accumulation.

[0032] Instructions for using this device:

[0033] The drug to be treated and the co-crystal form or stabilizer are added to the concave hole 40 of the mixing container 4 in proportion, and grinding media are added; the sealing cap 5 is covered and the reaction chamber is sealed by mechanical pressing; the acoustic resonance system is activated and low-frequency high-acceleration sound waves are applied to drive the grinding media to generate high-frequency shear motion, so that the drug is nano-sized or co-crystal reorganized; after the treatment is completed, the grinding media is separated and the nanocrystals or co-crystal products are collected.

[0034] The acoustic treatment time is 5-60 minutes, the frequency is 0-50 Hz, and the acceleration is 10-120 m / s², in order to achieve efficient nano-sizing or eutectic formation.

[0035] The drug is a poorly soluble drug (such as ibuprofen or griseofulvin), the cocrystallization product is saccharin, caffeic acid or succinic acid, and the stabilizer is at least one of polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), sodium dodecyl sulfate (SDS) or the like.

[0036] The nano-suspension has a particle size of 300-800 nm, the crystallinity of the eutectic product is ≥85%, and ≥60 different formulations can be screened simultaneously in a single batch.

[0037] The method is suitable for high-throughput eutectic screening in the laboratory, and the products can be directly used for X-ray diffraction (XRD) or differential scanning calorimetry (DSC) analysis.

[0038] This equipment is used to drive the shearing action between grinding media and drug particles through low-frequency, high-acceleration acoustic wave energy, enabling the efficient and homogenized preparation of single-batch, multi-component drug nano-suspensions or cocrystals. This equipment is suitable for the nano-sizing of poorly soluble drugs in the pharmaceutical industry (e.g., to improve bioavailability) and the development of drug-cocrystal precursors.

[0039] Example 1: Preparation of progesterone nanosuspension

[0040] 300 mg of progesterone raw material, passed through a 200-mesh sieve, was weighed and added to 30 mL of an aqueous solution containing 1% Tween. The mixture was thoroughly mixed to form a coarse suspension. Ten concave holes were randomly selected in the mixing container, and 1 mL of the coarse suspension was added to each hole. Then, 1 mL of 0.3 mm zirconia beads and one 0.5 cm diameter zirconia bead were added. After sealing with a cap, the container was fixed on a vibration table. The vibration frequency was set to 45 Hz, corresponding to an acceleration of approximately 100 g. After running the equipment for 30 minutes, the grinding media was removed, and the nano-suspension from each concave hole was collected. Dynamic light scattering (DLS) was used to characterize the average particle size of the nano-suspension. The results showed that the particle size of the nano-suspension in all 10 holes was between 800 and 950 nm. The above process was repeated twice, and the batch-to-batch average particle size difference RSD was found to be ≤5%. These experimental results indicate that this equipment can be used for high-throughput preparation of nano-suspensions and can provide reliable technical support for the efficient screening of nano-suspension stabilizers.

[0041] Example 2: Preparation of trimethoprim-sulfamethoxazole eutectic

[0042] Ten randomly selected wells in the mixing container were used. 20 mg of sulfamethoxazole and 24 mg of trimethoprim were added to each well. 5 μL of a 1:2 mixture of ethanol and ethyl acetate was added to each well, followed by 1 mL of 3 mm zirconia beads. After sealing with a cap, the container was fixed to a vibration table with a vibration frequency of 30 Hz and an acceleration of approximately 60 g. After running for 45 min, the grinding media was removed by sieving. X-ray powder diffraction (XPRD) analysis revealed new characteristic diffraction peaks and intensities. The results showed that eutectic formation occurred in all ten wells, and the positions and intensities of the characteristic diffraction peaks were essentially consistent. These experimental results indicate that this equipment can be used for high-throughput eutectic preparation and efficient screening of eutectic formations.

[0043] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this utility model, and not to limit it. Although this utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this utility model.

Claims

1. A high-throughput nano-suspension eutectic preparation device based on acoustic resonance, comprising a mixing container (4), a sealing cap (5), and an acoustic resonance system, characterized in that: The shape of the sealing cap (5) is adapted to the mixing container (4). The mixing container (4) has several recessed holes (40). The sealing cap (5) has several protruding posts (50). The side wall of the protruding post (50) is provided with an annular sealing ring. The acoustic resonance system includes a resonance platform and a fixing device and a support device. The resonance platform includes a vibration table (3) and a drive machine (6). The drive machine (6) is fixedly installed at the bottom of the resonance table (3). The mixing container (4), the sealing cap (5) and the resonance platform are fixedly installed together by the fixing device. The fixing device includes a square saddle clip (7). The mixing container (4) and the sealing cap (5) are installed in the square saddle clip (7). A square clip (9) is installed on the outer side of the end of the square saddle clip (7) and the side end of the vibration table (3). Screws (8) are installed on the upper and lower sides of the square clip (9).

2. The high-throughput nano-suspension eutectic preparation equipment based on acoustic resonance according to claim 1, characterized in that: Several of the protruding posts (50) are adapted to the concave holes (40).

3. The high-throughput nano-suspension eutectic preparation equipment based on acoustic resonance according to claim 1, characterized in that: The annular sealing ring can be made of either polytetrafluoroethylene or medical-grade silicone.

4. The high-throughput nano-suspension eutectic preparation equipment based on acoustic resonance according to claim 1, characterized in that: The concave holes (40) in the mixing container (4) are arranged in an array with a diameter of 10-20 mm, a depth of 0.75-15 mm, and a spacing of ≥1.0 times the diameter of the hole.

5. The high-throughput nano-suspension eutectic preparation equipment based on acoustic resonance according to claim 1, characterized in that: The support device includes a base (1), on which a vibration spring (2) is fixedly installed, and the bottom of the vibration table (3) is fixedly connected to the vibration spring (2).

6. The high-throughput nano-suspension eutectic preparation device based on acoustic resonance according to claim 1, characterized in that: Rotate the screw (8) to press the end of the square saddle clip (7) together with the side end of the vibration table (3).

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