Dry granulation purpose and granulation method

The purpose and method of granulation most solid dosage forms need to go through the "granulation" process Granulation technology is not only used in the preparation process of tablets, capsules, granules, etc., but also often needs to be made into granules in order to facilitate the processing of powders Moreover, auxiliary materials for direct tablet pressing are often required to be made into granules to ensure the quality and smooth production of drugs (1) the purpose of granulation (1) to make particles have good fluidity, and it is easy to realize automation, continuity and quantification in drug delivery, packaging and filling; (2) to prevent the separation phenomenon caused by the difference of particle size and density, which is conducive to the uniform mixing of various components (3) prevent dust flying in the operation process and adhesion on the wall of the device, avoid environmental pollution and loss of raw materials; (4) adjust the stack density, improve the solubility; (5) make the pressure transfer uniform in the tablet pressing process; (6) improve the efficacy and stability of the drug when the formula and operation are appropriate; (7) easy to take, etc Particles may be intermediates, such as pelletizing during tablet production, or products, such as granules The purpose of granulation is different, and the requirements are different or focused For example, the main purpose of tablet pressing particles is to improve the fluidity and compression formability, while the main purpose of granule and capsule preparation process is to improve the fluidity, prevent adhesion and flying, improve the mixing uniformity and improve the appearance In recent years, with the development of pharmaceutical industry, granulation technology has been greatly improved (2) the classification of granulating methods widely used in pharmaceutical production can be divided into two categories That is, wet granulation and dry granulation (1) wet granulation: a method for preparing particles by adding a binder to the raw material powder and making the powder agglomerate by the bridging or bonding effect of the binder Extrusion granulation, rotating granulation, fluidized bed granulation, stirring granulation, etc belong to wet granulation (2) dry granulation: no liquid is added into the raw material powder, and the combination force is generated by the effect of compression force to make the distance between particles close to each other The particles are directly compressed into the required particles according to a certain size and shape, or the powder is first compressed into flakes or plates, and then re crushed into the required size particles (3) the binding force between particles is formed by the aggregation of numerous particles (or crystalline particles) by a certain binding force In order to distinguish the original particles of raw materials from the manufactured particles, the former are called * particles and the latter are called second particles or particles In the process of granulation, the binding force between the * particles directly affects the strength, particle size, density and other powder properties of the second particle During granulation, the binding force between particles can be summarized as follows: (1) solid bridge - the solidification of local molten liquid due to pressure or friction, the crystallization of inter particle solution after drying and the solidification of inter particle adhesive (2) adhesion and adhesion of non flowing liquid -- binding force produced by the adsorption of adhesive (such as sugar, gum, gum, etc.); (3) bridging effect of flowing liquid -- binding force produced by capillary suction and surface tension of liquid between particles (4) attraction between particles -- mainly the intermolecular attraction (van der Waals force), electrostatic force, etc produced in the process of fine powder treatment; (5) mechanical tooth force -- when stirring or compressing fibrous and massive particles, the particles are combined by tooth, which is related to the particle structure In the above discussion, the binding force of solid bridge is strong UI, while the gravitational force between particles is weak UI Although the mechanical tooth force is large, it has little effect on the strength of particles Granulation technology and experience 1 Concept of granulation technology Granulation technology: it is a technology to process materials in the state of powder, melt, water solution, etc into particles of a certain shape and size The purpose of granulation: ① to improve the fluidity and facilitate the separation and tablet pressing; ② to prevent the segregation of components due to the difference of particle size density; ③ to prevent dust flying and adhesion on the wall of the device; ④ to adjust the bulk density and improve the solubility; ⑤ to improve the uniformity of pressure transmission in tablet production; ⑥ to be easy to take, carry and improve the commodity value Granulation methods: wet granulation and dry granulation (also known as one-step granulation) Among them, wet granulation uses more UI (most domestic and foreign pharmaceutical, food and chemical enterprises are using dry granulation) Application of granulation technology: UI is widely used in solid preparations, especially in granules and tablets 2 Granulation method (I) Wet granulation (most pharmaceutical, food and chemical enterprises at home and abroad are using dry granulation) Wet granulation: first, the soft material is made by adding adhesive or wetting agent into the drug powder, and then the wet particles are made by sieving, and then the whole particles are made after drying The particles made by wet method have the advantages of good surface modification, beautiful appearance, strong wear resistance, good compression formability, etc., and are widely used in the pharmaceutical industry Mechanism of wet granulation: first, the liquid in the binder wettes the surface of the drug powder to produce adhesive force between the powder particles, and then under the action of liquid bridging and external mechanical force, the particles of certain shape and size are made After drying, the UI is finally consolidated in the form of solid bridge Wet granulation mainly includes the process of making soft materials, making wet particles, drying wet particles and the whole particles 1 Soft material preparation: mix the raw and auxiliary materials weighed according to the prescription, and add a proper amount of wetting agent or adhesive The problems that should be paid attention to in soft material manufacturing: (1) the type and amount of binder should be determined according to the nature of the material; (2) the concentration and mixing time of the binder should be flexibly controlled according to different varieties; (3) the quality of soft material Due to the difference of raw and auxiliary materials, it is difficult to set a unified standard Generally, it is mastered by experience It can be lumped by hand, and it can be split by fingers (4) the length of wet mixing time has a great influence on the soft material of particles The longer the wet mixing time is, the greater the viscosity is and the harder the particles are made 2 Wet particle making: make the soft material pass through the screen to form a particle When the particles fall from the sieve holes as long strips, it indicates that the soft material is too wet, and the wet mixture or wetting agent is too much On the contrary, if the soft material is powdery after passing through the sieve hole, it indicates that the soft material is too dry, it should be adjusted properly Common equipment: swing granulator, rotary granulator screen: there are nylon wire, galvanized wire, stainless steel, plate four kinds of screen 3 Drying of wet particles: the screened wet particles shall be dried immediately to avoid caking or compression deformation (stainless steel plate can be used to spread out the prepared wet particles and turn them when they are placed to solve the problem of caking and deformation during storage) Drying temperature: it depends on the nature of raw materials, generally 50-60 ℃; for some drugs with stable moisture and heat, the drying temperature can be appropriately increased to 80-100 ℃ Degree of dryness: controlled by measuring moisture content The water content of granules is required to be no more than 2%; the proper water content of tablet granules is kept according to the difference of each specific variety, generally about 3% Drying equipment: commonly used heating drying equipment such as box type (such as drying room, oven), boiling drying, microwave drying or far infrared drying 4 Whole particle: after drying, the wet particles need to be screened to break up the lumped particles, so as to meet the particle size requirements of granules or tablet pressing requirements (1) granule: the part that can't pass through the sieve hole can be properly disintegrated with the sieve mesh less than 10 mesh (No.1 sieve) used for wet granule preparation, and then the particles between 10-80 mesh can be graded according to the lower limit of granularity specification and 60 mesh or 80 mesh (No.5 sieve) according to the granularity requirements; (2) tablet: the particle can be screened with larger mesh than the wet particle (II) dry granulation: the method of directly pressing the drug powder (diluent, etc if necessary) into a block with suitable equipment and then crushing it into the required size particles The method relies on the action of compression force to produce binding force between particles It can be divided into heavy pressing method and rolling method Heavy pressing method: also known as the large-scale method, is to press the solid powder on the heavy-duty tablet press to form a 20-25 mm diameter embryo, and then break it into the required size particles Rolling method: a rolling machine is used to roll the drug powder into pieces, which are broken into particles of a certain size by a granulator Dry granulation features: commonly used in heat sensitive materials, unstable drugs in contact with water and drugs easy to be compressed and shaped, the method is simple, labor-saving and time-saving However, attention should be paid to the possible crystal transformation and activity reduction caused by compression （3） granule made of traditional Chinese medicine: generally, it is usually made by rotating granulation 1 Granule made of fine powder of traditional Chinese medicine: when the dosage of the formula is not large, the traditional Chinese medicine can be ground into fine powder of more than 100 mesh, and the appropriate wetting agent or adhesive can be added to make soft material, and the granule can be made by sieving 2 Granulation by mixing thick extract and fine powder of medicinal materials: some medicinal materials are made into thick extract, the other medicinal materials are ground into fine powder, the two are mixed into soft materials, sieved, granulating and dried This method can use thick paste instead of adhesive, which is beneficial to reduce the volume of tablets and is widely used If the adhesive force is not enough when using only thick paste as adhesive, other adhesives can be added 3 Dry extract granulation: extract and prepare the medicinal materials (except the medicinal materials containing volatile components) in the formula Grind the dry extract into particles, or grind the dry extract into fine powder, and then add appropriate wetting agent (such as alcohol of appropriate concentration) to make soft material, and then make particles 3、 Factors affecting wet granulation 1 Properties of raw and auxiliary materials (1) fine powder, loose texture, poor drying and viscosity, low solubility in water; the adhesive with strong viscosity is selected, and the amount of adhesive is more (2) high solubility in water, strong viscosity of raw and auxiliary materials; select wetting agent or adhesive with small viscosity, and the amount of adhesive is relatively small (3) it is sensitive to humidity and easy to hydrolyze; it is not allowed to use water as the solvent of adhesive, but anhydrous alcohol or other organic solvent as the solvent of adhesive (4) it is sensitive to heat and easy to decompose; try not to use water as the solvent of adhesive, and choose alcohol with certain solubility as the solvent of adhesive, so as to reduce the drying time and temperature of particles (5) it is stable to humidity and heat; water with lower cost is selected as the solvent of adhesive 2 Wetting agent and adhesive wetting agents: the liquid that makes the material wet to produce enough strength of viscosity to facilitate the preparation of particles The wetting agent itself has no viscosity or weak viscosity, but it can wet the material and induce the viscosity of the material itself, so that it can agglomerate into soft material and make particles Such as distilled water and alcohol Adhesives: it can make the adhesive less or less