1. Physical properties of fillers
Empty gelatin capsules are widely used in pharmaceutical and nutritional supplement fields, and one of the key factors is the physical properties of the filler. Empty gelatin capsules are usually used to encapsulate powdered, granular, liquid or gel-like substances. Powder-based fillers are usually suitable for empty gelatin capsules, but the particle size, density and flowability of different fillers will affect the filling effect of the capsule. For example, powders with larger particles may encounter difficulties during the filling process, resulting in uneven filling of the capsule or voids. Therefore, in this case, it may be necessary to add flow improvers such as silicon dioxide or talc to the filler to improve its flowability and prevent agglomeration.
In addition, the hygroscopicity of the powder may also affect the performance of the empty gelatin capsule. Some fillers have high hygroscopicity, such as herbal powders, which can cause the capsule shell to soften, swell, or even rupture. Therefore, in order to ensure the stability of the capsule, special encapsulation techniques may be required, or capsule shell materials with higher moisture resistance may be selected. Liquid fillers require special attention to the compatibility of their viscosity with the capsule shell, because high-viscosity liquids may cause the capsule to deform or rupture. In this case, you can choose a reinforced capsule, such as a double-layer capsule, to improve the capsule's carrying capacity and stability.

2. Chemical stability
Empty gelatin capsules have good chemical stability, but compatibility with different fillers still requires special attention. The active ingredients in some drugs or health products may react chemically with gelatin capsules, affecting the solubility of the capsule and the overall effect of the product. For example, the acidic components in some drugs may react with gelatin, causing the capsule shell to rupture, or changing the release rate and bioavailability of the drug. Similarly, strong alkaline substances may also have a negative impact on the stability of gelatin capsules, thereby reducing the solubility of the capsule or affecting its efficacy.
To avoid this problem, many manufacturers choose to use modified gelatin or other types of capsule materials, such as HPMC (hydroxypropyl methylcellulose capsules), which can avoid reactions with acidic or alkaline substances and have better moisture resistance and stability. In addition, some active ingredients, especially herbal extracts or plant essences, may react with gelatin to cause the active ingredients to lose their activity. Choosing capsule materials with good antioxidant capacity is also an effective way to avoid problems.

3. Effects of moisture and temperature
Empty gelatin capsules are very sensitive to moisture and temperature changes. Moisture absorption may cause the capsule shell to swell or soften, affecting the appearance and solubility of the capsule. Especially for areas with high humidity or long-term storage environments, the capsule may deform or stick, resulting in unstable release of the drug. The effect of moisture on empty gelatin capsules is not only reflected in the physical properties of the capsule shell, but may also interact with the filler, thereby affecting the quality of the drug or supplement. For example, some fillers contain ingredients that are easily affected by moisture, such as sugars or plant powders, which may deteriorate or become ineffective when humidity is high.
High temperature is also a key factor affecting the stability of empty gelatin capsules. Gelatin has a low melting point (about 35°C to 40°C). Under high temperature conditions, empty gelatin capsules may lose hardness, resulting in faster dissolution or capsule rupture. When designing the storage and transportation conditions of empty gelatin capsules, special attention should be paid to controlling humidity and temperature, and trying to avoid the effects of high temperature and humid environment on capsules. For fillers that need to withstand high temperature or high humidity environments, choosing the right encapsulation material or capsule type (such as plant capsules or modified gelatin capsules) is an effective solution.

4. Biocompatibility
The biocompatibility of empty gelatin capsules is often one of the reasons why they are widely used in the pharmaceutical and nutritional supplement fields. The main ingredient of empty gelatin capsules is animal gelatin, which is usually derived from pig skin or cow bones. It has good biocompatibility and is compatible with most drugs or nutritional supplement ingredients. However, some special ingredients, such as enzymes, proteins, or certain active chemicals, may have adverse reactions to gelatin, resulting in its stability and bioavailability being affected. For example, enzyme ingredients may react with the protein structure of gelatin capsules, causing the capsule to rupture or the drug to be unable to be effectively released.
Some people may have allergic reactions to animal-derived products (such as porcine gelatin). Therefore, in order to meet the needs of a wider range of consumers, more and more manufacturers have begun to launch plant-based capsules (such as HPMC capsules). These plant-based capsules are more friendly to vegetarians and consumers with allergies, and perform well in terms of biocompatibility. Empty gelatin capsules have good biocompatibility for most drugs and supplements, but when selecting fillers, the interaction between ingredients must be fully considered to ensure the effectiveness and safety of the product.

5. Matching of particle size and density
The particle size and density of the filler are important factors affecting the filling effect of empty gelatin capsules. Fillers with larger particle sizes (such as certain granular or crystalline substances) have poor filling effects in capsules, which may lead to uneven filling or excessive voids in the capsule, thus affecting the accuracy of the dosage. To avoid this problem, the filler usually needs to be pre-processed, such as crushing or sieving, to ensure that its particle size is suitable for the volume requirements of the capsule. By controlling the particle size of the filler, the efficiency of the filling process can be improved and the uniformity of the capsule can be guaranteed.
The density of the filler also affects the design and filling efficiency of the capsule. A higher density filler may require the use of a larger capsule to ensure sufficient space for the drug or nutrient. On the other hand, a low-density filler may require more capsules to achieve the same dosage. This means that the density of the filler needs to be matched to the capsule size to ensure dosage accuracy. Fillers with lower density (such as some herbal powders) may accumulate or clump inside the capsule, which may affect the release rate and effect of the drug. Therefore, manufacturers usually choose the appropriate capsule size based on the properties of the filler and take measures during the production process to ensure the stability and uniformity of the filler.

6. Hygroscopicity of fillers
The hygroscopicity of fillers is another important factor affecting the compatibility of empty gelatin capsules. Many natural medicines and supplement ingredients, such as plant powders and sugars, have strong hygroscopicity, which can cause deformation or cracking of the capsule shell. The absorption of moisture not only affects the structure of the capsule itself, but may also have a negative impact on the active ingredients of the drug or supplement. For example, highly hygroscopic fillers may absorb moisture from the air, causing oxidation, deterioration or unstable release rate of the ingredients.
In order to avoid the adverse effects of moisture, many manufacturers have adopted moisture-proof technologies, such as using thickened capsules or moisture-proof coatings to increase the moisture resistance of capsules. In addition, desiccants (such as silica gel bags) are also common solutions that protect the stability of capsules and fillers by absorbing moisture from the air. In terms of packaging and storage, a low humidity environment is required to prevent the capsules from being affected by humid air, thereby ensuring the quality of the empty gelatin capsules and the effectiveness of the medicine.