#capsulemanufacturing

Capsules have long been one of the most adaptable dosage forms in pharmaceuticals - capable of delivering everything from fine powders and pellets to semisolids and liquids. For decades, gelatin has been the go-to material for capsule shells, prized for its biocompatibility, robustness, and compatibility with high-speed filling lines. Gelatin capsules typically disintegrate within minutes in biological media, making them reliable performers for immediate-release formulations.

Yet as the pharmaceutical landscape evolves, so do its demands. Patient preferences, regulatory scrutiny, and the rise of complex, moisture-sensitive molecules are prompting manufacturers to look beyond gelatin. Hydroxypropyl Methylcellulose (HPMC) - a plant-derived, cellulose-based polymer - has emerged as a compelling alternative that addresses many of gelatin's inherent limitations.

The Limitations Driving Change

Despite gelatin's widespread adoption, it carries a set of challenges that can complicate modern formulation development.

Moisture sensitivity is among the most significant. Gelatin capsule shells contain an inherent moisture content of 13–16%, which creates compatibility issues with hygroscopic or moisture-sensitive active pharmaceutical ingredients (APIs). Water is one of the most potent accelerants of drug degradation, and a high-moisture shell puts vulnerable formulations at risk from the moment of encapsulation.

Chemical reactivity is another concern. Gelatin's amino acid and protein composition makes it susceptible to cross-linking reactions - most notably the Maillard reaction - when free amino groups interact with carbonyl-containing compounds in the capsule fill. Cross-linking can compromise capsule solubility, delay disintegration, and ultimately alter drug release profiles in ways that are difficult to predict or control.

Safety and regulatory concerns add another layer of complexity. Gelatin is derived from animal collagen, raising concerns about Transmissible Spongiform Encephalopathy (TSE) and Bovine Spongiform Encephalopathy (BSE). These issues create regulatory hurdles and restrict the use of gelatin capsules in markets where animal-derived excipients face stricter scrutiny.

Finally, gelatin is incompatible with vegetarian, vegan, and halal/kosher-conscious consumers - a growing demographic in both pharmaceutical and nutraceutical markets.

Why HPMC Is the Answer

HPMC directly addresses each of these pain points, offering a scientifically sound and commercially practical alternative.

Superior Moisture Control

HPMC capsule shells contain only 3–8% inherent moisture - roughly half that of gelatin. This dramatically reduced moisture content makes HPMC capsules far more suitable for hygroscopic APIs and moisture-sensitive formulations. Crucially, HPMC capsules maintain their mechanical integrity and elasticity even in low-humidity environments, ensuring product stability across varying storage and distribution conditions. This is a material advantage across the entire pharmaceutical supply chain, from the manufacturing floor to the patient's medicine cabinet.

No Cross-Linking Risk

As a cellulose derivative, HPMC contains no proteins or amino acids, making it chemically inert relative to capsule fill components. Cross-linking reactions - including the Maillard reaction - simply cannot occur. The result is a capsule that maintains consistent solubility, reliable disintegration, and predictable drug release rates throughout the product's shelf life. For long-term storage scenarios, this stability is not just convenient - it is essential.

Broad Formulation Compatibility

HPMC capsules are pH-independent and non-ionic in nature, making them compatible with a wider range of formulation types than gelatin. They work effectively without the addition of gelling agents, and are well-suited to liquid-fill applications, hygroscopic compounds, and APIs that interact adversely with gelatin components. This versatility gives formulators more latitude in design without the need to re-engineer around shell compatibility.

Regulatory and Safety Advantages

Because HPMC is plant-derived, it eliminates the TSE/BSE concerns associated with animal-sourced gelatin. HPMC capsules also present a lower risk profile in the context of nitrosamine formation - an area of increasing regulatory focus globally. Unlike gelatin, HPMC lacks the amino groups that can react with nitrosating agents, reducing the likelihood of nitrosamine-related contamination. This makes regulatory submissions cleaner and gives manufacturers greater confidence in meeting the evolving requirements of bodies like the FDA and EMA.

Clean Label and Consumer Appeal

HPMC capsules contain no gelatin, gluten, wheat, starch, or animal by-products, making them suitable for vegetarian, vegan, halal, and kosher applications. As consumer demand for clean-label, plant-based healthcare products continues to accelerate, HPMC capsules allow pharmaceutical and nutraceutical brands to align their formulations with these preferences - without compromising on technical performance.

Manufacturing Considerations

A common misconception is that switching from gelatin to HPMC capsules requires significant changes to existing filling equipment or processes. In reality, HPMC capsules are designed to run on standard high-speed capsule filling machinery with minimal adjustment. Their dimensional consistency and mechanical properties closely match those of gelatin capsules, allowing manufacturers to transition smoothly without major capital expenditure.

That said, the lower moisture content of HPMC shells does require attention to humidity control during processing and storage, particularly in dry climates. Proper environmental controls ensure that the capsules maintain their optimal physical characteristics throughout the manufacturing process.

The Strategic Business Case

Beyond formulation science, the shift to HPMC capsules makes strategic sense for manufacturers looking to future-proof their portfolios. Key drivers include:

Expanding market access: Vegetarian and clean-label compliance opens doors to consumer segments and geographic markets where gelatin-based products face barriers.

Regulatory readiness: A proactive approach to animal-derived excipient risks and nitrosamine compliance reduces late-stage development surprises.

Supply chain resilience: Plant-based raw materials diversify sourcing away from animal-derived supply chains, which are subject to disease outbreaks, geopolitical risk, and fluctuating commodity prices.

Pipeline alignment: As the industry moves toward more complex biologics, peptides, and moisture-sensitive molecules, HPMC capsules are structurally better suited to protect next-generation APIs.

Conclusion

HPMC capsules represent more than a material upgrade - they are a strategic response to the evolving demands of pharmaceutical manufacturing. By addressing the moisture, chemical reactivity, and safety limitations of gelatin, HPMC enables manufacturers to formulate with greater confidence, serve broader patient populations, and navigate a tightening regulatory environment with less friction.

Why Wurster systems strain under high-dose substrate loading

Within a Wurster process, pellets cycle vertically through a spray column where solution is layered incrementally. Fluidising air circulates particles between the spray region and the drying zone.

As layer thickness increases, solvent evaporation becomes the primary constraint. Raising concentration to reduce solvent increases viscosity and nozzle blockage risk, while lowering concentration raises overages and extends drying time.

PEPT and CFD-DEM studies demonstrate that particles spend only 12–29% of each cycle inside the Wurster tube. The remaining time involves circulation and heat/mass transfer outside the spray zone, slowing the overall spray-dry rhythm relative to rotor systems.

Tangential rotor spraying integrates wetting and drying

Modern Wurster-capable fluid beds often allow rotor integration for tangential spraying. Rotor operation fundamentally reshapes particle motion. With airflow, centrifugal force, and gravity acting together, particles follow a spiral path around the chamber.

Shear forces and particle collisions distribute droplets effectively, increasing exposed surface and limiting local solvent pooling.

Unlike intermittent Wurster exposure, all pellets remain in continuous motion. Therefore, layering, mixing, and drying proceed in parallel.

Synchronised rotary variables are essential

Spray rate, atomisation pressure, and rotor speed govern PSD and growth patterns. High spray rates combined with low atomisation pressure yield larger droplets that evaporate slowly, forming larger agglomerates and broadening PSD5. Higher pressures generate finer droplets that narrow PSD.

Rotor speed adds a moisture-dependent mechanical influence. At low spray rates, high speeds break apart dry agglomerates. At high spray rates, high speeds densify wet, deformable pellets, enlarging them5.

Rotor systems tolerate elevated deposition, but independently increasing either parameter can destabilise the process.

Dry powder layering shifts liquid to adhesive function

Even in tangential spraying, evaporation governs process limits. Dry powder layering changes the liquid’s role from carrier to binder.

By co-spraying binder and API powder, liquid per pellet is minimised and drying time shortened.

Relative to solution spraying, powder layering can reduce solvent consumption by up to 80% and decrease process duration by nearly 50%.

60% shorter processing for a global CDMO

A regulated-market CDMO recently developed a Wurster process for Lansoprazole Capsules.

Spray concentration was limited to 25% to avoid clogging. Lower concentration required more solvent for the same drug loading, while overages were capped at 5%. Increasing solution volume was not acceptable.

Partnering with ACG Laboratories, they transitioned to rotor-based dry powder layering.

A rotor and powder feeder were added to the existing unit, enabling rapid mass increase with minimal changes and modest investment.

Results included:

60% reduction in process time (12 to nearly 5 hours) 70% reduction in solvent usage Removal of 5% material overage 100% pellet coating efficiency

Conclusion

Wurster systems deliver uniform coatings effectively. Yet high-dose layering is constrained by evaporation and intermittent exposure.

Rotor-based tangential spraying enables simultaneous wetting, mixing, and drying. Dry powder layering further lowers solvent requirements by redefining liquid as adhesive.

Summit Rx transforms your product ideas into market-ready supplements through our expert capsule manufacturing services. We combine advanced technology, skilled craftsmanship, and strict quality protocols to produce capsules that stand out for their quality and reliability. Our capabilities include a variety of capsule types—gelatin, vegetarian, delayed-release, and colored options—so your product can meet specific functional and branding needs. At Summit Rx, capsule manufacturing isn’t just about production; it’s about creating supplements that consumers trust and return to. Our process ensures that active ingredients are preserved for maximum efficacy, with consistent dosing in every capsule. We provide packaging solutions that enhance shelf appeal while maintaining product integrity. Whether you’re a growing brand or a large-scale manufacturer, our flexible production volumes and competitive pricing make us an ideal partner. Summit Rx is dedicated to helping you succeed in the competitive supplement industry with capsules that deliver both performance and appeal.

Bilayer tablets offer a refined solution for delivering multiple drugs within a single dosage form. By integrating two distinct formulations, each layer can release its contents at a different rate or respond to specific physiological conditions. This dual-delivery approach has become a staple for complex therapies where compatibility and release timing are essential.

This format allows for the integration of immediate and extended-release mechanisms, which enhances therapeutic outcomes while simplifying patient regimens. Though the concept is elegant, the execution requires deep technical understanding and robust process control.

Production Insights: How Bilayer Tablets Are Made

Manufacturing begins with a rotary press fitted with a dual-feeding system. The bottom layer is partially compressed to retain its surface texture for adhesion. The second layer follows, and the entire tablet is fully compressed to form a uniform and robust unit.

Although the steps appear simple, challenges quickly emerge. These include inconsistent layer weights, poor adhesion between layers, and contamination risks. Of these, delamination—a separation of layers—remains the most critical quality concern.

Manufacturing Pitfalls

Delamination typically stems from insufficient bonding, different material behaviors, or poor compression control. The result is a compromised tablet that may not deliver drugs as intended. Environmental influences like heat and moisture can accelerate the problem during storage and transport.

Layer weight uniformity is vital to ensure accurate dosing. Variations in granule characteristics or die fill levels can lead to dosage inconsistencies, especially in the second layer. Disparities in mechanical properties such as hardness and elasticity can lead to defects like lamination or tablet breakage.

While lubricants are crucial for preventing sticking, excessive use—especially in internal formulations—can hinder bonding. This is especially true for tablets containing polymers, which are more sensitive to lubricant interference.

Refining Formulation and Processing

Material compatibility is the cornerstone of success. Ingredients should have similar compaction profiles to prevent stress imbalances. When that's not feasible, shared excipients can improve interfacial harmony.

Compression must be finely tuned. The first layer needs only light compaction to ensure a textured surface, promoting adhesion. Too much pressure results in a slick surface that resists bonding. The second layer must then be compressed with care to secure the final structure.

Modern rotary presses offer sophisticated control over compression force and fill volume. These machines can track variations in real-time and adjust settings on the fly, reducing variability and enhancing product consistency.

An external lubrication strategy, such as coating die surfaces with lubricant, minimizes the use of internal lubricants, preserving tablet integrity and improving yield.

Technological Breakthroughs

Predictive simulation tools like finite element analysis have revolutionized tablet design. These models anticipate mechanical failures and guide optimal material and process selection, reducing trial-and-error phases in development.

Innovations such as buffer zones between APIs or the use of multi-functional excipients have further expanded the design possibilities, offering enhanced control over drug interactions and release kinetics.

Addressing Recurring Problems

A well-balanced layer weight ratio—commonly 1:1 or 1:2—can reduce interfacial stress. Light pre-compression of the first layer ensures better adhesion without compromising its ability to bond.

Weight inconsistencies are best resolved through equipment that measures and adjusts fill volumes for each layer in real-time. This guarantees dosage accuracy and helps meet regulatory quality standards.

Conclusion

Bilayer tablets reflect the evolution of pharmaceutical delivery systems. They offer a patient-friendly, efficient method of delivering complex therapies in a single dose.

Bin blenders are used for blending of dry powders during the process of tablet and capsule manufacturing in various different industries.