Navigating Oral Solid Dosage Manufacturing: From Traditional Batch to Advanced Continuous Operations

The Foundation of Modern Drug Delivery

When patients take a tablet or capsule, they’re receiving one of the most reliable drug delivery systems ever developed. Oral solid dosage (OSD) forms—tablets, capsules, soft gels, and other ingested products—account for the majority of pharmaceutical prescriptions worldwide. This dominance stems from three fundamental advantages: ease of administration, product differentiation, and a century of refined manufacturing expertise.

The history of oral solid dosage manufacturing dates back to 1842, when Englishman William Brockedon patented compressed tablets of sodium and potassium carbonate for use as a calcium supplement and antacid. Today, manufacturers have perfected this delivery system into a sophisticated science involving precise formulation, advanced equipment, and validated processes.

Understanding the Core Components of OSD

Every oral solid dosage product consists of an active pharmaceutical ingredient (API)—the drug substance itself—combined with various excipients, fillers, and dry powder ingredients. These components must be mixed, processed, and formed into a final product that delivers consistent drug performance across every single dose.

The two predominant OSD forms are tablets and capsules. Tablets are created through compression and can be coated or uncoated, while capsules are constructed through a coating process where the drug substance and supporting ingredients layer around a seed material. Each form can offer different bioavailability profiles and release characteristics—some medications are designed for immediate release, while others use sustained, controlled, or extended-release mechanisms depending on therapeutic requirements.

The overarching manufacturing objective remains constant: ensure that every individual tablet or capsule contains the same distribution of ingredients with consistent dissolution and bioavailability to guarantee safety and efficacy.

Processing Platforms: Choosing the Right Approach

Oral solid dosage manufacturing employs several distinct processing platforms, each suited to different formulation requirements and product characteristics. The four most widely adopted platforms in modern facilities are wet granulation, dry granulation, direct compression, and particle coating.

Wet Granulation: Combining Liquids and Solids

Wet granulation joins powder particles together using a liquid binder solution—typically aqueous—sprayed into the process vessel. This platform operates through either high-shear or low-shear mechanisms.

High-shear wet granulation employs a motor-driven blade or impeller system that creates intense mixing forces, typically implemented in vertical or horizontal high-shear granulators. Low-shear wet granulation introduces the binding solution via spray atomization in a fluid bed granulator, creating a gentler interaction.

Key benefits of wet granulation:

• Reduces fine particles and dust during processing
• Improves powder flowability for downstream operations
• Enables predetermined granule sizing with uniform ingredient distribution
• Facilitates tablet core compaction by binding granules together
• Provides controlled dissolution profiles through granule structure
• Increases bulk density for optimized body absorption

Essential equipment:

• Granulator (high-shear or fluid bed models)
• Solution delivery system with spray nozzles
• Fluid bed dryer for post-granulation drying

Dry Granulation: Solid-to-Solid Compaction

Dry granulation creates dense granules by compacting powders under high-force pressure without adding liquid binders. A roller compactor—the primary equipment—applies variable-intensity compression through adjustable press rolls, creating a ribbon of compacted material that is then sized.

This platform is especially valuable for moisture-sensitive APIs and formulations where water introduction is problematic.

Key benefits of dry granulation:

• Eliminates dust through particle densification
• Improves bulk density and powder flow characteristics
• Maintains predetermined granule size and ingredient consistency
• Enables effective tablet core formation
• Controls dissolution profiles through granule density
• Accommodates APIs incompatible with wet processing

Essential equipment:

• Roller compactor with integrated sizing capability

Direct Compression: Minimal Processing

Direct compression homogeneously blends powders through gentle tumbling in a blender without physically altering the starting granules. This low-intensity mixing process uniformly distributes ingredients through particle movement and rotation.

This platform is ideal for formulations where ingredient stability is paramount and minimal processing is preferred.

Key benefits:

• Straightforward ingredient combination and homogeneity
• Eliminates physical transformation of powder particles
• Reduced processing time and equipment complexity

Essential equipment:

• Tumble blender (various configurations available)
• Charging and discharging systems

Particle Coating: Building Layered Formulations

Particle coating applies active drugs and/or sealers onto individual granules or beads through atomized liquid spraying in a fluid bed processor. This platform creates sophisticated multi-layer compositions for encapsulation.

Key benefits:

• Creates smooth, low-abrasion surfaces
• Improves powder flowability
• Masks taste and odor characteristics
• Protects ingredients from light, air, and moisture
• Enables systematic, delayed release of active components

Essential equipment:

• Fluid bed coater for layer application
• Solution delivery and drying systems

The Manufacturing Workflow: Critical Unit Operations

Oral solid dosage manufacturing follows a well-defined progression of unit operations that has remained fundamentally consistent for over a century, though equipment and technologies continue to advance.

Ingredient Dispensing and Formulation

The first operation involves accurately weighing APIs, excipients, fillers, and miscellaneous materials, then dispensing them into process vessels. Because powder handling generates dust, this operation must occur in controlled environments using local exhaust ventilation (LEV) enclosures, downflow booths, or isolators.

A critical challenge involves managing raw materials that arrive in diverse packaging—bags, drums, boxes, and supersacks—requiring material handling equipment like lifts, inverters, and manipulators alongside careful attention to operator safety and ergonomics.

Granulation and Drying Operations

This operation combines ingredients using the selected processing platform to achieve desired granule characteristics. The workflow begins with ingredient dispensing into the granulation train (wet or dry), proceeds through the mixing/compaction process, and concludes with drying to remove residual moisture.

Space requirements present a practical challenge—granulation and drying typically demand tall spaces to utilize gravity for feeding and receiving. Many facilities address this by integrating both operations vertically or renovating existing spaces to accommodate the equipment footprint.

Blending and Premixing

The blending operation combines active ingredients with excipients and lubricants to achieve homogenous ingredient distribution. This may occur multiple times: pre-blending before granulation and post-blending (final blend) before compression.

Loading and unloading present operational challenges that can introduce inefficiencies, contaminants, and dust while potentially causing blend separation. Solutions include intermediate bulk container (IBC) systems where blending occurs in the same transfer container used upstream and downstream, requiring only a single discharge. Through-the-wall blender configurations—with drive mechanisms outside the controlled environment and only the product vessel in the process room—reduce facility space requirements and accelerate cleaning cycles.

Compression and Encapsulation Operations

This unit operation transforms the formulation into its final dosage form. Equipment includes tablet presses or encapsulators, metal detection systems, dedusters, tablet testing devices to verify weight/thickness/hardness, and containment solutions.

Like granulation, space requirements can be substantial. Strategic facility design using a high-hat configuration around the tablet press while keeping the surrounding ceiling lower enables gravity feed from transfer bins while minimizing overall room volume and associated air-handling requirements.

Tablet Coating

Following tablet compression, film or functional coatings improve taste, swallowability, and product protection. Functional coatings may incorporate additional active ingredients applied to the tablet exterior.

This operation requires careful tablet handling to prevent damage during loading and discharge. Ergonomic assist devices or gravity discharge systems effectively manage tablets moving to and from collection bins.

The Modern Frontier: Continuous Manufacturing

Traditional oral solid dosage manufacturing operates in batch mode—individual unit operations occur sequentially with manual material transfers between stages. Continuous manufacturing (CM) fundamentally reimagines this workflow by integrating individual operations into a single, continuous equipment train that feeds material through all processing steps as a closed process.

Advantages of Continuous Operations

Continuous manufacturing significantly reduces production time and eliminates several risk factors associated with batch processing:

• Removes manual material transfers between equipment, reducing ergonomic strain
• Eliminates contamination risks inherent in open batch processes
• Minimizes human operator errors in testing and quality control
• Reduces production delays from material movement and staging
• Enables rapid capacity adjustment to meet changing demands
• Produces higher quality products through integrated process control

Continuous System Architectures

Fully Integrated Continuous Systems begin at bulk powder handling and conclude with coated tablets. The entire workflow—from excipient and API feed through processing platforms (direct compression, wet granulation, or dry granulation) through conventional compression, automated testing, tablet relaxation, continuous coating, and final collection—operates as one unified, controlled process.

Partially Integrated and Hybrid Systems typically span from powder feed to tablet compression, using traditional batch operations for bulk powder handling and tablet coating. This configuration offers a more accessible entry point to continuous manufacturing while maintaining core efficiency gains.

Advanced End-to-End Systems represent the frontier of pharmaceutical manufacturing innovation. These systems integrate drug substance synthesis with drug product manufacturing for comprehensive process continuity. Raw chemical synthesis feeds directly into crystallization, filtration, drying, and sizing, which seamlessly connects to continuous drug product processing platforms, compression, testing, relaxation, coating, and collection—all within a fully controlled, integrated system.

Implementation Considerations

Fully integrated systems are among the most complex to deploy but represent an expanding number of global installations offering the widest capability range. Partially integrated and hybrid systems provide excellent entry points with balanced complexity and benefits. Direct compression configurations remain the most straightforward to implement. Advanced end-to-end systems offer transformational potential but demand the greatest technical and operational sophistication.

Strategic Success Factors

Successful oral solid dosage manufacturing—whether upgrading existing facilities or constructing new ones—depends on several universal considerations:

Collaboration and Communication: The most successful projects involve close coordination among facility owners, engineering teams, construction partners, and equipment vendors throughout planning and implementation phases.

Early Operator Involvement: Manufacturing operators understand daily operations better than engineers. Their input during decision-making stages proves critical to ultimate success.

Pre-Qualification Strategy: Comprehensive vendor evaluation includes profile compilation, budget establishment, bid solicitation, presentation review, and formal shortlisting procedures.

System Integration Planning: Addressing process, equipment, and facility integration factors early in design phases prevents costly modifications and ensures cohesive system performance.

Vendor Relationship Management: Strategic sole-sourcing of key equipment can streamline integration, support, and ongoing optimization.

Oral solid dosage manufacturing continues evolving as technology advances and regulatory expectations increase. Whether employing traditional batch operations or implementing cutting-edge continuous manufacturing systems, the fundamental goal remains constant: delivering safe, effective medications in a form that patients can easily take and trust.