Dry granulation is to directly make powder raw materials into granular products that meet user requirements. After granulation, the bulk density increases significantly, which can not only control pollution, but also reduce powder waste, improve the appearance and fluidity of materials, and facilitate storage and transportation. , can control the solubility, porosity and specific surface area and other purposes. Dry granulation is especially suitable for water-sensitive ingredients and heat-sensitive ingredients. This article intends to discuss the common problems of dry granulation from two aspects of process and equipment.
1.1 Selection of excipients
Dry granulation excipients should have good fluidity and compression molding properties, that is, dry adhesion function.1.1.1 Microcrystalline cellulose
It is also used as an excipient for wet granulation. The product made by the spray drying method has better fluidity and larger drug holding capacity (that is, adding more drugs will not have a serious adverse effect on its fluidity and compression formability).
1.1.2 Pregelatinized starch
Partially pregelatinized starches are called compressible starches. It has good fluidity, angle of repose <40°, good compression molding performance, and disintegration effect. The compressed tablet disintegrates quickly and has good drug release performance. Although the hardness of the tablet pressed with pregelatinized starch as the diluent is better, the friability of the tablet is not very good. If it is used in combination with microcrystalline cellulose, the effect will be better. Pregelatinized starch has its own lubricity, and its fluidity is better than that of starch, microcrystalline cellulose, and dextrin.
1.1.3 Magnesium stearate
It is recommended to add 1.0% to 1.5% magnesium stearate before dry granulation to solve the sticky roller problem. For granules, a little more hard magnesium can be added inside; if tablets or capsules are dry granulated, as long as it can improve or solve the problem of material sticking to the roller, add less hard magnesium, because the tables or capsules will also be compressed or filled, and hard magnesium will be added for anti-sticking, so that the total amount of hard magnesium in the prescription will be increased.
1.1.4 Direct pressure accessories
If you want convenience, directly use direct-pressed excipients, such as direct-pressed lactose from JRS, direct-pressed starch from Colorcon, direct-pressed microcrystalline cellulose from FMC, direct-pressed mannitol, xylitol, sorbitol and other polyols from Roquette. The effect of this kind is very good, and the varieties with anti-moisture absorption need to add micropowder silica gel.
1.1.5 Composite accessories
There are a variety of excipients for direct tablet compression abroad, which are mainly composed of sugars. For example, "Ludipress" is composed of lactose, PVP, and cross-linked PVP, and is formed into fine particles; another example is "Di-Pac", which is mainly composed of sucrose; "Soludexl5" is composed of maltodextrin, etc.; "Emdex" contains 90% to 92% of glucose and 2.25% of maltose. The angle of repose of the first-class composite excipients is around 30° or <30°, the fluidity is good, the compression formability is good, the appearance of the tablet, disintegration and drug dissolution are all good, which can greatly simplify the tablet production process.
1.1.6 Lactose
Lactose, calcium hydrogen phosphate, calcium sulfate, copovidone, PEG, etc. can be used for dry granulation and direct compression of powder.
1.2 Particles are too hard
It should be noted that if the roller pressure is too high during the dry granulation process, the pressed dry granules will be too hard. If the next step is to make tablets, the dry granules will be too hard and the compressibility will be lost. As a result, a larger pressure will be required to compress the tablet. For forming, the machine vibrates greatly; if it is a capsule, the dry granules are too hard and the compressibility is lost, which leads to the material being thrown away during the capsule filling process due to the failure of the powder column, so that the difference in the filling volume far exceeds the standard.