Last week, we hosted a webinar with EKATO on the science behind capsule shell mass manufacture. It brought together a host of formulation scientists, process engineers, and manufacturing professionals from across the industry. The strong turnout reflects something we hear constantly in practice: that shell mass is where a surprising share of softgel quality problems begin, and by the time a mass reaches the die rolls, most of what defines its behaviour has already been decided.
To cover both sides of shell mass manufacture, the session paired two perspectives. Yanitsa Miteva, founder of The Science of Soft Capsules and partner at Trias Pharma, covered the formulation science and the critical quality attributes that determine whether a mass will run at all. Andreas Reimer, Product Manager of UNIMIX at EKATO Systems, walked through the manufacturing process.
Gelatin, Plasticizers and Critical Quality Attributes
Yanitsa opened with a rather curious yet apt analogy: shell mass manufacture is a little like baking a cake. To continue with her metaphor, she elaborated by saying that you essentially need the recipe, the ingredients, the equipment, the oven, and the right temperature. Naturally, a lot can go wrong here, just like when you bake a cake.
On gelatin itself, two points stood out. The USP and EP definitions are broad enough that materials with meaningfully different properties all satisfy them. Type A (acid-processed) and Type B (alkaline, typically bone) differ in acidic amino acid composition, isoelectric point, and molecular weight distribution. Moreover, bloom and viscosity are not interchangeable, as bloom characterises the gel strength in solid state, while viscosity characterizes the flowability in liquid state.
Gelatin alone melts above 100 °C, while encapsulation runs at roughly 38–42 °C at the wedge. To bring the melting temperature of the gelatin to lower ranges, a plasticizer is added. Glycerol is the strongest candidate here, she argued, though unsuitable for some formulations; water is effective but too volatile to be used alone. The rule is to bring the melting range into the processing window and no further, and here, over-plasticising is a common mistake because it can bring stickiness among other effects.
She also explained why shell mass has both a minimum and a maximum hold time. At around 60 °C, hydrolysis reduces molecular weight while the helical network continues to build: use the mass too early or too late, and gel strength may be insufficient.
The attributes that usually go unmeasured
Most shell mass is released on viscosity (typically 8,000–15,000 mPa·s) and appearance. Both are useful, and both describe the liquid state of the mass, which is why a shell mass can comply with the viscosity specification and still have poor processability. But two further attributes describe the gel state, and neither is routinely characterised:
Elasticity: resistance to deformation. Faster cooling at the casting drums forms smaller triple helical structures and gives higher elasticity.
Tensile strength: stress withstood before the ribbon ruptures. More, longer and stronger helical structures give higher tensile strength. They are formed under slower cooling.
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Manufacturing the Shell Mass
Andreas took the process end to end, using the EKATO UNIMIX gel melter as the example. Because gelatin is shear-sensitive, the gel melter uses a Paravisc agitator without the homogenizer found in the standard design; in a 50-litre comparison with a high-viscosity carbopol gel, it mixed roughly ten times faster than a standard cross-beam design.
The process breaks into five controlled steps:
Liquid phase preparation. Water and plasticizer heated above 60–70 °C. Uneven heating here affects gelatin wetting later.
Gelatin addition. Gelatin is drawn in under vacuum, with a guiding tube preventing deposits on the shaft and vessel wall. The target is wetting without lumps.
Dissolution. A double jacket plus secondary heating loop, for complete dissolution without local overheating.
Deaeration. The most critical step. Vacuum must remove entrapped air, but excessive vacuum leads to excessive evaporation of water.
Discharge. Checked against defined criteria for homogeneity, viscosity, temperature and absence of lumps and bubbles.
Andreas closed with a diagnostic summary as well:
Viscosity too high: too high gelatin concentration / or water loss under vacuum
Lumps: rapid gelatin addition, insufficient wetting, or insufficient mixing / mixing duration
Air bubbles: insufficient vacuum, inadequate deaeration time, excessive agitation, or air entering through the transfer system
The underlying point, though, is that shell mass quality is never controlled by a single parameter. It emerges from the interaction between formulation, temperature exposure, agitation, and deaeration, which is why defects chased one variable at a time tend to return.
Questions from the Audience About CDMOs
The Q&A surfaced several recurring themes worth highlighting:
What is softgel capsule shell mass made of?
Gelatin forms the structural matrix, purified water acts as solvent, and a plasticizer keeps the shell flexible. Colourants are added depending on the product. The exact composition depends on the fill mass properties and the target capsule properties.
What is the difference between Type A and Type B gelatin?
Type A is acid-processed, typically from pig skin or bovine hide tissue; Type B is alkaline-processed, typically from bovine bones. Both comply with the pharmacopoeias and share the same principal amino acids (glycine, proline and hydroxyproline) that determine the gelling capacity. They differ in acidic amino acid composition, which shifts the isoelectric point into the alkaline range for Type A and the acidic range for Type B, and in molecular weight distribution..
Why do softgel shell formulations need a plasticizer?
Gelatin alone has a melting and glass transition range above 100 °C, while encapsulation runs. A plasticizer lowers those ranges into the processing window on the encapsulation machine ( approximately 38–42 °C at the wedge) and keeps the film elastic. Water is highly effective but volatile, so it evaporates during encapsulation and drying and cannot serve as the sole plasticizer. Glycerol is the most widely used plasticizer.
What is the most critical process parameter in capsule shell mass manufacture?
Mixing duration: the gelatin has to be completely dissolved in the water/plasticizer mix.
Deaeration. Air entrapped during gelatin dissolution has to be removed under vacuum, with axial circulation carrying bubbles to the surface and sufficient headspace for foam to develop. The difficulty is that the step pulls in two directions: too little vacuum leaves bubbles that compromise ribbon quality and shell integrity, while too much evaporates water and alters viscosity and the final shell properties.
Holding time: a minimum holding time is required to allow the formation of a three-dimensional network and support gel strength, but too long holding times at elevated temperatures may counteract this and decrease processability.
Why does a shell mass fail to process even when viscosity is within specification?
Because viscosity describes the shell mass characteristics in its liquid state. How it behaves on the machine also depends on two gel-state attributes that are rarely characterised: elasticity, the resistance to deformation, and tensile strength, the stress the mass withstands before breaking. Both depend on the triple helical structures in the gel, and they respond to the molecular weight distribution of gelatin in the shell mass, which in turn depends on holding time and temperature, as well as to the cooling rate on the machine.
This webinar was made possible through collaboration between The Science of Soft Capsules and EKATO Systems. EKATO will host an in-house seminar in the US early next year featuring a live gel melting process, with details to follow on their LinkedIn page.
Stay tuned for our next webinar! Follow us on LinkedIn or subscribe to our newsletter to be the first to know about our upcoming expert sessions on softgel capsule development.
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FAQs: CDMOs in Softgel Capsules
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Out of 759 mapped pharma CDMOs worldwide, only 82 offer softgel capabilities, and just 8 are fully dedicated to softgels. In Europe, 32 CDMOs operate softgel facilities, distributed evenly across regions.
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The global softgel market is expected to grow at approximately 7.5% CAGR, while contract manufacturing within the segment is growing faster at 8.6%.
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The most frequent mistakes include inflated cost calculations padded "just to be safe," insufficient understanding of the competitive landscape, lack of a proper RFQ and costing tool, and weak cross-functional alignment within the CDMO itself.
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Know-how, track record, and team experience matter as much as equipment. Documentation quality and review processes are often underestimated but frequently determine project success. Analytical development capacity, particularly for dissolution, is a common bottleneck. Soft factors like responsiveness and transparency during the RFQ phase tend to predict execution quality.
