Ease of swallowing, odor and taste masking, improved absorption, enhanced bioavailability, improved resistance to drug degradation, and high atmospheric stability are noted advantages of soft gel capsules for treating inflammation, cardiovascular, and other diseases. And, due to the flexibility of the substance, soft gels can perform well for complex formulations, including DEA-controlled substances, hormones, and products with multiple APIs. These benefits are driving the market landscape, valued at $7.62 billion in 2021¹ and projected to reach $13 billion by 2030.² Creating a soft gel capsule that performs as intended is extremely complicated and difficult, and truly is an art form. Skilled scientists will perform early development studies, such as gel film evaluations, gel fill compatibility, solubility evaluations, and forced degradation studies to simulate what will happen under cGMP conditions.

A key aspect of any soft gel is the gel mass quality used in the formation of the capsule shell. Make sure your CDMO has suitable vessels for gel mass manufacturing. Ensuring consistency in the formulation and reducing foaming are critical aspects. The gel mass is prepared by dissolving the gelatin in water at approximately 80°C and under vacuum.

This process is parallel to the compounding activities associated with the drug. Equipment, such as a Lee Kettle with a built-in homogenizer, can compound up to 600 liters of product. This vessel will help form the active fill matrix with dispersion and dissolution of the drug substance in the non-aqueous vehicle.

The encapsulation process occurs when two separate ribbons are cast through the rollers to form the gel ribbons. Rotary dies aid the combination of the gel ribbon with the liquid fill matrix, heating to about 40°C. The capsules are cut automatically from the gel ribbon by the rims around each of the die rollers. During encapsulation, in-process testing occurs to evaluate fill weights, seam, and ribbon thickness.

The capsules then travel to and through tumble driers to complete the drying process. The capsules are spread out onto trays and placed in drying tunnels at approximately 20% relative humidity. The soft gels can be kept in drying tunnels for two to three days or up to two weeks to ensure equilibrium in drying is achieved. Capsules will remain in a drying tunnel to check for critical quality attributes, such as moisture content and hardness, before going to primary packaging.