Dry granulation technology First, the purpose of the dry granulation operation is as follows: 1. Make the material into the desired structure and shape; 2. For accurate quantification, formulation and management; 3. Reduce the dust pollution of the powder; 4. A non-segregation mixture of different types of particle systems; 5. Improve the appearance of the product; 6. Prevent agglomeration during the production of certain solid phase materials; 7. Improve the flow characteristics of the separated raw materials; 8. Increase the volumetric quality of the powder for easy storage and transportation; 9. Reduce the risk during handling of toxic and corrosive materials; 10. Control the dissolution rate of the product; 11. Adjust the void ratio and specific surface area of ​​the finished product; 12. Improve heat transfer and help burn; 13. Adapt to different biological processes. Second, the powder material particle shape properties In the granulation process by the strong pressure granulation method, the powder is compacted into a compact state by applying an external force in a defined space. The forces that produce stable agglomeration are bridging forces, low viscosity liquid adhesion, surface forces, and interpolymerization. The success of the agglomeration operation depends, on the one hand, on the efficient use and transfer of the applied external force and on the other hand on the physical properties of the particulate material. Particle shape refers to the image formed by the contour boundary of a particle or the points on the surface. The shape of the particles directly affects other properties of the powder, such as fluidity, filling, etc., and is also directly related to the behavior of the particles in the mixing, storage, transportation, sintering and other unit processes. In the project, people have different requirements on the shape of the particles according to different purposes. For example, the high-speed dry-pressing method of wall and floor slab powder requires rapid filling and smooth exhaust in the mold, so spherical particles are suitable; concrete aggregate requires high strength and tight filling structure, so the shape of the gravel is hoped. It is a regular polyhedron. Conversely, the shape of the particles varies depending on the process of formation. For example, a simple oscillating jaw crusher produces more flake products; a powder prepared by spray drying is mostly spherical particles. Therefore, various particle shapes need to be quantitatively described to show the difference. On the other hand, in theoretical research and industrial practice, irregularly shaped particles are often assumed to be spherical to facilitate calculation of particle size, and experimental results are easily reproduced. For this reason, it has become one of the main reasons for the great difference between theoretical calculations and actual situations. Therefore, it is generally necessary to multiply the particle size in the theoretical formula by the coefficient indicating the influence of the shape. Particles encountered in nature and industrial production are not ideal rule bodies, such as spheres, which vary in shape: spherical, cubic, platy, discs, prismoidal, scaly (flaky), granular, rodlike, needle-like, acicular, fibrous, dendritic, sponge, blocky, sharp angle Sharp, round, porous, aglomelate, hollow, rough, smooth, fluffy, nappy. Geometry described in mathematical language requires at least two types of data and combinations thereof, in addition to three types of data for special occasions. The commonly used data includes representative values ​​of the particle size in the three-axis direction, a contour curve of the two-dimensional image projection, and related data of the solid geometry such as the surface and the volume. It is customary to refer to various dimensionless combinations of particle sizes as shape indices, and the relationship of various variables of solid geometry is defined as shape factors. 1 shape index 1) Uniformity (proportion) The ratio of the two dimensions of the particle - the elongation N and the flatness M can be derived from the ratio between the three axes L, B, T: Length N = long diameter / short diameter = L / B (≥ 1) Flatness M = short diameter / thick height = B / T (≥ 1) When L=B=T, the above two indices of the cube are equal to 1 2) space filling factor The volume fullness Fv, also known as the volume factor, represents the ratio of the volume of the circumscribed cube of the particle to the volume V of the particle, namely: Fv=LBT/V (≥1) The reciprocal of Fv can be seen as the extent to which the particles are close to the cube, with a limit of 1. The area fullness Fb, also known as the shape magnification factor, represents the ratio of the projected area A of the particle to the area of ​​the small circumscribed rectangle of the zui, namely: Fb=A/LB (≤1) Degree of sphericity The sphericity or true sphericity indicates the extent to which the particles are close to the sphere: Ψ0=πDV2/S (≤1) DV=(6V/π)1/3 Where DV means that the volume of the particles of the particles is comparable, S is the surface area of ​​the particles, and V is the volume of the particles. For irregularly shaped particles, when it is difficult to determine the surface area, practical sphericity can be used, namely: Ψ0′= diameter of a circle equal to the projected area of ​​the particle/diameter of the small circumscribed circle of the particle projection (≤1) Degree of circularity Circularity, also known as the contour ratio, indicates the extent to which the projection of the particle is close to the circle: ψc=πDH/L DH=(4A/π)1/2 L represents the perimeter of the particle projection. Roundness Indicates the degree of angular wear of the particle, which is defined as: Round angle = ∑ri/NR (≤1) Where ri is the radius of curvature on the contour of the particle; R is the radius of the inscribed circle; N is the number of angles. Shape factor Surface area shape factor Фs = surface area of ​​the particles / (average particle size) 2 = S / dp2 (> 1) Volume shape factor Фv = volume of particles / (average particle size) 3 = V / dp3 (≤ 1) 3) Specific surface area shape factor Φ=surface area shape coefficient/volume shape factor=Фs/Фv (>1) For spherical particles, the above three shape factors are: Фs=πd02/d02=π Фv =πdo3/6d03=π/6 Φ=Фs/Фv =6π/π=6 It must be pointed out that since the particle size representation method is large, different shape coefficients can be defined by different particle size representation methods. In addition, the particle size value is related to the measurement method of the particle size, and therefore the value of the shape factor varies depending on the measurement method. Therefore, when using the shape factor, it is necessary to pay attention to the specific expression of the particle diameter. 4) Roughness factor The aforementioned shape factor is a macroscopic amount. If you look at the particles microscopically, you will find that the surface of the particles tends to be uneven, with many tiny cracks and holes. The roughness of the surface is expressed by the roughness coefficient R: R = actual surface area of ​​the particle microscopic / apparently considered as the macroscopic surface area of ​​smooth particles (> 1) The roughness of the particles is directly related to the particle properties such as friction, adhesion, adsorption, water absorption and porosity between the particles and the solid wall. It is also one of the main factors affecting the wear of the workpiece in the granulation operation equipment. Therefore, the roughness factor is a parameter that cannot be ignored. At present, the import of dry granulators mainly includes Japan Friendship Company, Alexander of Germany, and Fitzpatrick Company of the United States. For dry granulation or direct compression, excipients with good adhesion and compressibility should be selected. This is conducive to the stability of the production operation and the quality of the finished product. Lactose has good compressibility, and the appearance of the tablet is good; sucrose has good compressibility, but it may absorb moisture; MCC has good adhesion; compressible starch, good compressibility, Liquidity is also good, it can be used as a must; mannitol has good compressibility and fluidity; dextrin has good adhesion. It is recommended to use compressible starch, lactose, dextrin, MCC, according to a certain proportion of the prescription, of course, also consider the nature of the main drug, it is estimated that there will be more satisfactory results. The dry granulation and powder direct compression sheeting materials should have good fluidity and compression moldability, that is, dry adhesion. Microcrystalline cellulose is also used in wet granulation excipients. The product prepared by the spray drying method has better fluidity and the medicine capacity is large (that is, the addition of more medicines does not seriously adversely affect its fluidity and compression moldability). The partially pregelatinized starch of the pregelatinized starch is called a compressible starch. This product is made of starch, its fluidity is good, the angle of repose is <40°, the compression molding is good, and it has disintegration effect. The pressed tablets disintegrate quickly and the drug release performance is good; this product has its own lubrication. The effect is small. When using this product, it should contain proper amount of water, otherwise the hardness of the tablet is insufficient. When adding lubricant to improve the appearance of the tablet, if magnesium stearate is used, the dosage should be minimized, otherwise the hardness of the tablet will be affected. Stearic acid has less effect on the hardness of the tablet. Tablets pressed with this product as a diluent have better hardness, but the friability of the tablets is not so good. For example, when combined with microcrystalline cellulose, the effect is better. Lactose (spray dried product, etc.), calcium hydrogen phosphate, calcium sulfate, etc. can be directly granulated by a dry granulation method and powder. There are a variety of excipients for direct compression in foreign countries. Most of the medicines collected by the medical education network are mainly composed of sugars. For example, the aforementioned “Ludipress†consists of lactose, PVP and cross-linked PVP, and is finely granulated; For example, "Di-Pac" is mainly made of sucrose: "Soludexl5" is composed of maltodextrin or the like: "Emdex" contains 90% to 92% of glucose and 2.25% of maltose. The repose angle of the superior composite excipients is about 30° or less than 30°, the fluidity is good, the compression molding property is good, the appearance, disintegration and drug dissolution of the tablets are good, which can greatly simplify the tablet production process. . So far, there is no domestic high-quality composite auxiliary materials listed in China, and it is urgent to fill the gap. Ganoderma lucidum extract,Senna leaf powder，Fritillaria Extract Fufeng Sinuote Biotechnology Co.,Ltd. , https://www.sntbiology.com