Theory and Factors of Caking in Powder Formulations
The theory of caking in crystalline powders is based on the crystal bridge theory and capillary adsorption theory, which describes a process of “hard caking” related to the surface processes (adsorption, solidification) of the powder. It is generally believed to be caused by the internal properties of the powder, formed at the contact points of particles, primarily depending on the surface state (physical and chemical properties of the surface).
Caking in amorphous powders is mainly related to the secondary thermodynamic transitions of the powder, representing a process of “soft caking”. Therefore, it is more dependent on the thermal properties of the powder (microscopically manifested as molecular thermal motion), relying more on the overall properties of the powder rather than its shape and particle size. Factors such as moisture, molecular weight, and molecular structure inherently affect the glass transition temperature, making them significant influences on the caking of amorphous powders.
Most powder formulations contain both crystalline and amorphous powders, with factors affecting caking including internal and external factors. Internal factors include the particle size and strength of the powder; if the powder particles have high strength, uniformity, and smooth surfaces with minimal dust, and if the storage time is short, the contact points between powder particles will be reduced, thereby decreasing the likelihood of crystal bridge formation and caking. External factors refer to humidity, temperature, pressure, and storage time. As temperature, pressure, and humidity change during production, storage, and use, the area of crystal interlinking between grains and the frequency of product dissolution and recrystallization increase, leading to more crystal bridges forming between particles, thus causing caking. Therefore, in general, powder formulations should not be stored in humid and hot environments; the greater the pressure during storage, the closer the particles are to each other, making it easier to form “bridges”; and the longer the storage time, the more severe the caking phenomenon.
Current Methods for Preventing Caking in Powder Formulations
Optimization of production processes. By optimizing production operations, the factors contributing to caking in powder formulations can be mitigated. Different drying processes can be employed for different products to reduce moisture content, improve packaging conditions and methods, use moisture-proof packaging materials, and control the temperature, relative humidity, stacking height and weight, and storage time of the products.
Use of anti-caking agents. Anti-caking agents are substances that can maintain the flowability of materials during storage and handling. In the production process of powder formulations, anti-caking agents can be applied through surface spraying or direct addition, forming a hydrophobic protective film on the powder surface, which prevents the product from exchanging moisture with the environment and hinders the formation of crystal bridges during the recrystallization process of crystalline powders, ultimately preventing caking. Anti-caking agents can be classified into five major categories based on the raw materials used.
Inert powders are a type of anti-caking agent that consists of water-insoluble substances with a large surface area, which do not dissolve in water and do not chemically react with the raw materials. They are used in appropriate proportions to dust the product, allowing them to adsorb onto the powder surface. Although they cannot form a continuous inert layer on the powder surface to completely prevent caking, they can limit moisture exchange between powder particles or between the product and the atmosphere, thereby reducing caking. Common inert powders are mostly inorganic substances, such as diatomaceous earth, kaolin, clay, talc, and aluminum silicate. This method is cost-effective but requires a large amount of addition and has poor water solubility, which can affect product quality, making it less commonly used.
Inorganic salt anti-caking agents are certain inorganic salts that can partially or completely hydrate the moisture in the product, inhibiting crystal bridging and capillary adsorption caused by moisture changes, making them most suitable for crystalline powder formulations.
Organic surfactants or surface-active agents are chemical substances that alter surface phenomena by reducing the surface tension of solvents. The molecules of surfactants have both hydrophilic and hydrophobic functional groups, which can reduce the surface tension between the liquid and solid phases, allowing the liquid phase to combine and penetrate into the mixed powder particles.
Non-surfactant or hydrophobic anti-caking agents work by forming a waterproof film on the surface of powder particles to prevent moisture absorption. These anti-caking agents are mainly organic hydrophobic agents, such as paraffin, mineral oil, and various resin polymers, which do not exhibit surface activity and work better at lower temperatures. However, at higher temperatures, the effectiveness of the hydrophobic layer decreases rapidly, as it cannot completely prevent moisture absorption by powder particles. When temperatures are high, this can lead to the destruction of the hydrophobic layer, resulting in severe caking. These anti-caking agents are more expensive and difficult to handle.
Composite anti-caking agents are mixtures primarily composed of surfactants, combining the advantages of the aforementioned anti-caking agents while compensating for their disadvantages, thus providing the best anti-caking effect and being widely used.
Current Application Status of Anti-Caking Technology in Powder Formulations
Currently, veterinary pharmaceutical companies undergo GMP reviews, but some companies, due to concerns about cost and output, use relatively low-end equipment and simpler processes, resulting in poor moisture control. Additionally, the temperature and humidity differences between northern and southern regions, as well as significant variations in temperature and humidity within the same region across different seasons, make it nearly impossible to completely prevent moisture absorption during production, sales, and use. Relying solely on optimizing production processes to prevent caking in powder formulations yields limited results and can only serve as a supplementary measure.
Anti-caking agents not only effectively solve the caking problem in powder formulations, improving product flowability, but also enhance the aesthetic quality of the products. They have been adopted by most powder formulation manufacturers. However, there are still several issues in the research and application of anti-caking agents: there is currently no unified standard for powder caking theory, and in-depth research is needed on the mechanisms of caking and the action mechanisms of anti-caking agents to provide a theoretical basis for the development of anti-caking agents; there is no targeted use of anti-caking agents during production, with most employing simple mixing processes that make uniform mixing difficult, leading to reduced anti-caking performance; high usage costs hinder the widespread application of anti-caking agents; and there is no comprehensive standard for measuring the quality of anti-caking agents used by various manufacturers, nor are there established standards for quality testing of treated powder formulations.
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