Plasticizers in Soft Gelatin Capsule Shell Formulations
Plasticizers in Soft Gelatin Capsule Shell Formulations
Gelatin alone cannot form films suitable for manufacturing soft gelatin capsules. Therefore, plasticizers need to be added to modify its properties — such as fluidity, elasticity, or rigidity — thereby improving the processability of gelatin films during production and the stability of the final soft capsule products throughout their shelf life.
The amount of plasticizer used depends on the type of gelatin material, capsule size, and filling type; however, using high concentrations of plasticizers may cause physical repulsion between the plasticizer and the gelatin polymer structure. Water is always used as a plasticizer component in shell formulations (accounting for 30–40% w/w in wet shell formulations), which is essential for forming the gelatin structure and obtaining gelatin masses with appropriate viscosity.
Due to its volatility (only 4–10% w/w remains in the final product), non-volatile plasticizers are also added to shell formulations, comprising 15–30% w/w of the wet shell and 0.3–1.0% w/w of dry gelatin.
The presence of non-volatile plasticizers is particularly critical during the drying step: plasticizers with high water content will migrate to the external environment, which alters the formed gelatin shell and subjects it to stress. Glycerol (85% and 98% w/w) is regarded as a reference plasticizer regardless of the gelatin type used. This is because it has a low molecular weight, high hygroscopicity, strong plasticizing efficiency, good compatibility, and low volatility — properties that enable the formation of a stable thermoreversible gel network. Nevertheless, it is typically used in oil-based filler formulations. Its plasticizing ability mainly stems from direct interaction with gelatin, while its hygroscopicity provides an additional indirect moisturizing effect.
Gelatin films using glycerol as a plasticizer exhibit low moisture resistance and high oxygen permeability. Sorbitol is primarily used in capsule formulations based on polyethylene glycol (PEG), as PEG is insoluble in sorbitol, which reduces the migration of PEG to the capsule shell.
Additionally, it is suitable for capsule formulations containing volatile components to minimize their permeation through gelatin capsules. Sorbitol acts as an indirect plasticizer: it does not interact with gelatin but functions as a humectant.
Its plasticizing ability is lower than that of glycerol, and it may crystallize under medium to low humidity conditions. Different grades of non-crystalline sorbitol exhibit varying compatibility with gelatin and plasticizing capacities; these differences depend on the content of hydrogenated galacto-oligosides and sorbitan (i.e., sorbose). Sorbitol products with high sorbose content — such as Sorbitol Special (SPI Pharma) and Anidrisorb or Polysorb (Roquette) — possess high plasticizing ability, comparable to that of glycerol.
On the other hand, combining sorbitol containing large amounts of hydrogenated oligosaccharides (e.g., maltitol) with glycerol can enhance the chewability and dissolution rate of soft capsules, making this combination an excellent choice for chewable products. Other plasticizers that can be used include propylene glycol (PG), low-molecular-weight polyethylene glycol (PEG), xylitol, maltitol, and mannitol. Compared with glycerol and sorbitol, PG has a stronger plasticizing capacity but also brings negative effects — it makes film formation more difficult.
In fact, shells containing PG exhibit high viscosity, and a lower encapsulation temperature must be used to form an optimal ribbon structure. Furthermore, due to PG’s high volatility, PG can negatively impact the film formation and mechanical properties of gelatin ribbons during the stabilization period.
Regarding PEG: low-molecular-weight PEGs (200, 300, or 400 kDa) have higher plasticizing capacity because these PEGs possess a higher ratio of hydroxyl groups that form hydrogen bonds with gelatin chains and a higher hygroscopicity grade. Over time, these PEGs migrate to the exterior of the gelatin film, causing phase separation (blooming or reddening) and rendering the transparent gelatin film opaque. High-molecular-weight PEGs inherently have higher opacity.
To avoid these incompatibilities, low-and high-molecular-weight PEGs should be used in combination with saccharin or PG. Oleic acid, triethyl citrate, acetyl triethyl citrate, tributyl citrate, and acetyl tributyl citrate can also serve as plasticizers. Although oleic acid has poorer plasticizing capacity and compatibility with gelatin materials compared to hydrophilic plasticizers — and may cause phase separation during drying — this phase separation can be reduced by adding emulsifiers such as lecithin. Additionally, the use of hydrophobic plasticizers usually results in opaque gelatin, and the opacity is proportional to the plasticizer concentration.
Reference:
Naharros-Molinero, A., Caballo-González, M. Á., de la Mata, F. J., & García-Gallego, S. (2024). Shell formulation in soft gelatin capsules: Design and characterization. Advanced Healthcare Materials, 13(1), 2302250. https://doi.org/10.1002/adhm.202302250
