Seal Coating Before Enteric Coating: Is It Necessary?

Introduction

Enteric coating is a widely used pharmaceutical technology designed to protect drug substances from the acidic environment of the stomach and delay drug release until the dosage form reaches a suitable region of the gastrointestinal tract. However, the successful development of an enteric-coated tablet depends not only on the enteric polymer but also on the interaction between the tablet core, coating materials, tablet manufacturing process.

One important formulation consideration is whether a film seal coat, also known as a subcoat or intermediate coating layer, should be applied before the enteric coating.

Is film coating mandatory before enteric coating?

The answer is no. A separate film seal coat is not universally mandatory for all enteric-coated tablets. However, it may be beneficial or necessary for specific formulations to improve compatibility, reduce interfacial interactions, support coating adhesion, and maintain the intended drug-release characteristics.

The decision should be based on formulation development studies, compatibility assessments, process performance, and dissolution results rather than a universal manufacturing rule.

Understanding the Difference Between Film Seal Coating and Enteric Coating

Although both processes involve applying a polymer film to a tablet, their primary functions are different.

What is Film Seal Coating?

Film seal coating is an intermediate coating layer applied to the tablet core before the functional enteric coating.

Depending on the formulation, it may serve several purposes:

Separate the drug-containing core from the enteric polymer.
Reduce direct chemical or physicochemical interactions between the core and the enteric coating.
Limit the migration of certain components across the coating interface.
Improve surface characteristics and support subsequent coating application.
Provide a degree of protection against moisture or the coating medium when the selected film has suitable barrier properties.

Hydroxypropyl methylcellulose (HPMC), also known as hypromellose, is one example of a polymer that may be used for an intermediate coating, depending on compatibility and the intended function.

A seal coat should not automatically be considered a complete moisture barrier. Its protective performance depends on the polymer, film thickness, formulation, and processing conditions.

What is Enteric Coating

Enteric coating is a functional coating designed to resist the acidic gastric environment and permit drug release under specified intestinal or higher-pH conditions.

Common enteric-coating polymers include:

Methacrylic acid copolymers.
Hydroxypropyl methylcellulose phthalate (HPMCP).
Cellulose acetate phthalate (CAP).
Polyvinyl acetate phthalate (PVAP).

The selection of the polymer depends on the desired dissolution threshold, drug properties, manufacturing process, and product performance requirements.

Unlike a conventional seal coat, the enteric layer provides the principal pH-dependent gastro-resistant function.

Tablet Coating Structure

A simplified structure of an enteric-coated tablet containing a separate seal coat is shown below:

Layer 1: Enteric coat
The outer functional layer responsible for resistance to gastric conditions and pH-dependent drug release.

Layer 2: Film seal coat
An optional intermediate layer that may provide separation or protection between the core and enteric polymer.

Layer 3: Tablet core
Contains the active pharmaceutical ingredient (API) and excipients.

The seal coat is located between the core and the enteric layer. Its inclusion should be justified by the specific formulation and manufacturing requirements.

Not every enteric-coated tablet requires all three layers. A formulation may be successfully developed with a direct enteric coating if the core, polymer, and coating process are compatible.

Five Scientific Reasons to Apply a Film Seal Coat Before Enteric Coating

1 Reducing Direct Interaction Between the API and Enteric Polymer

One important reason for applying a seal coat is to reduce direct contact between the tablet core and the enteric polymer.

Certain enteric polymers contain acidic functional groups. If the tablet core contains an alkaline API or excipient, an undesirable interaction may occur at the core–coating interface.

Such interactions may influence the coating properties, adhesion, stability, or drug-release behaviour.

An appropriately selected intermediate film can provide physical separation between the core and the enteric layer, potentially reducing these interactions.

However, the benefit must be established experimentally because not every API–polymer combination presents a compatibility problem.

2 Limiting API or Excipient Migration

During aqueous coating, water can penetrate the tablet surface and mobilize soluble components within the core.

Depending on the physicochemical properties of the formulation, an API or excipient may migrate toward the tablet surface or into the developing coating layers.

This migration can alter the composition of the coating interface and potentially affect coating performance.

A suitable seal coat may reduce such migration by providing an intermediate barrier. Nevertheless, its effectiveness depends on the permeability of the film, the solubility and mobility of the migrating component, and the coating conditions.

It should not be assumed that every seal coat prevents API migration completely.

3 Controlling Interfacial pH Effects

The local chemical environment at the interface between the tablet core and enteric coating can influence polymer behaviour.

For example, a highly acidic tablet core may create an acidic microenvironment near the enteric film. This can affect the dissolution behaviour of certain pH-dependent enteric polymers.

Crotts and colleagues investigated enteric-coated tablets containing a highly water-soluble organic acid. Their study demonstrated that applying a seal coat could improve drug release in phosphate buffer compared with tablets coated without a seal coat under the investigated conditions.

This finding illustrates that the tablet core can influence the performance of the enteric layer and that an intermediate coating may be useful for selected formulations.

A seal coat should not, however, be described as a universal pH-control layer. Its effect depends on the core composition, polymer chemistry, and resulting interfacial conditions.

4 Improving Surface Characteristics and Coating Uniformity

Tablet cores may exhibit surface irregularities, porosity, or local differences in wettability.

An appropriately formulated seal coat may help produce a more suitable surface for subsequent enteric coating. Depending on the formulation and process, this can support more uniform application of the functional coating layer.

Potential benefits include improved surface coverage and reduced variability associated with the underlying tablet surface.

However, coating uniformity also depends on other critical variables, including:

Tablet core quality and geometry.
Spray rate and atomization.
Inlet air temperature and product temperature.
Pan speed and tablet bed movement.
Suspension properties and coating weight gain.
Drying and curing conditions, where applicable.

Therefore, a seal coat alone cannot guarantee uniform enteric coating.

5 Providing an Additional Protective Layer During Processing

A seal coat may provide an additional degree of protection against the coating medium or processing environment.

This can be particularly relevant when the API or one or more excipients are sensitive to moisture or when direct exposure to the enteric-coating suspension creates a formulation risk.

Nevertheless, a conventional film seal coat is not necessarily an effective moisture barrier. The barrier properties must be evaluated for the selected polymer and coating thickness.

If moisture protection is the primary objective, the formulation scientist should select and evaluate a film specifically for that function rather than assuming that any film coating will provide sufficient protection.

When Is a Seal Coat More Likely to Be Necessary?

A separate seal coat deserves particular consideration when formulation development identifies one or more of the following conditions:

Formulation or process concern	Potential role of a seal coat
Alkaline API or excipients with potential interaction with acidic enteric polymers	May reduce direct contact and interfacial interaction
Highly acidic, water-soluble tablet core	May reduce undesirable core–coating interfacial effects
Water-soluble API or excipients susceptible to migration during aqueous coating	May limit migration, depending on film properties
Poor adhesion or unsuitable surface characteristics	May improve the substrate for subsequent coating
Moisture-sensitive formulation exposed to aqueous coating	May provide additional protection if the film has suitable barrier properties

These are formulation-development considerations, not automatic indications. Each proposed benefit should be assessed using relevant experimental evidence.

When May Direct Enteric Coating Be Acceptable?

Direct application of the enteric coating may be appropriate when:

The tablet core is compatible with the selected enteric polymer.
The coating medium does not adversely affect the API or excipients.
The enteric layer adheres adequately to the tablet core.
Coating uniformity and integrity are acceptable.
The finished product meets its dissolution and stability requirements.

Eliminating an unnecessary seal-coating step may simplify manufacturing, reduce processing time, and avoid additional material and operational costs.

However, process simplification should never compromise the product’s quality, safety, or intended drug-release characteristics.

The decision to omit a seal coat should be supported by development data and an appropriate control strategy.

Example: Enteric-Coated Diclofenac Sodium Tablets

Diclofenac sodium is a useful example for discussing enteric-coating formulation considerations.

A seal coat may be evaluated in a diclofenac sodium tablet formulation if development studies identify a relevant core–coating compatibility issue, migration concern, adhesion problem, or processing-related risk.

The following approach may be used during formulation development:

Step 1: Characterize the tablet core

Assess the API and excipients, including their physicochemical properties, moisture sensitivity, solubility, and potential interactions with the selected coating materials.

Step 2: Evaluate the enteric polymer

Determine whether the selected polymer and coating vehicle are compatible with the core and whether direct coating produces an acceptable film.

Step 3: Compare direct coating and seal-coated formulations

Prepare suitable development batches using a direct enteric-coating approach and, where justified, an approach incorporating a seal coat.

Step 4: Evaluate coating performance

Assess coating appearance, surface coverage, adhesion, defects, and relevant physical or chemical attributes.

Step 5: Perform dissolution testing

Evaluate acid-stage resistance and subsequent buffer-stage drug release using the applicable pharmacopoeial method and product-specific acceptance criteria.

Step 6: Assess stability

Determine whether the selected coating system maintains the required product quality throughout the proposed shelf life.

A seal coat should be selected only if the results demonstrate a meaningful benefit or if it is otherwise necessary to achieve the required product performance.

This example is illustrative. It does not establish that every diclofenac sodium tablet requires a seal coat.

Critical Quality Attributes to Evaluate

The success of an enteric-coated tablet should be demonstrated through appropriate quality assessments.

Appearance and Coating Integrity

Inspect the tablets for cracking, peeling, chipping, roughness, colour variation, and other coating defects.

Acid Resistance

The enteric-coated dosage form should meet the applicable acid-stage requirements. The specific test medium, duration, and acceptance criteria should follow the relevant pharmacopoeial monograph or approved product specification.

Buffer-Stage Dissolution

After the acid stage, evaluate drug release in the specified buffer medium.

The dosage form must release the drug according to its intended delayed-release profile and applicable acceptance criteria.

Assay and Related Substances

Where appropriate, evaluate assay and degradation products to determine whether the coating process adversely affects the chemical quality of the drug product.

Stability

Assess the product under appropriate stability conditions to determine whether the coating system maintains its performance over time.

A seal coat is not a substitute for demonstrating the functionality of the final enteric-coated dosage form. Compendial testing of delayed-release products generally addresses acid-stage resistance and subsequent buffer-stage performance.

Common Misconceptions About Seal Coating

Misconception 1: Film coating is always mandatory before enteric coating.

Correction: A separate seal coat is not universally required. Its necessity depends on the formulation and process.

Misconception 2: A seal coat provides the enteric function.

Correction: The enteric layer provides the principal pH-dependent gastro-resistant function. A conventional seal coat does not replace it.

Misconception 3: Every seal coat prevents moisture penetration.

Correction: Moisture-barrier performance depends on the polymer, formulation, film thickness, and processing conditions.

Misconception 4: Applying a seal coat automatically improves dissolution.

Correction: A seal coat may improve or alter drug-release behaviour in certain formulations, but its effect must be evaluated experimentally. An unsuitable intermediate layer may introduce additional resistance to drug release or create other performance issues.

Misconception 5: If the tablet looks smooth, the seal coat is unnecessary.

Correction: Visual appearance alone cannot establish compatibility, acid resistance, dissolution performance, or long-term stability.

Regulatory and GMP Considerations

The inclusion or removal of a seal-coating step should be addressed through a science-based pharmaceutical development and quality risk management approach.

Relevant considerations include:

Documented formulation and process rationale.
API–excipient and API–polymer compatibility.
Assessment of coating process parameters and potential failure modes.
Appropriate in-process controls and finished-product testing.
Acid-stage and buffer-stage dissolution performance.
Stability data supporting the proposed coating system.
Change control and regulatory assessment when modifying an approved commercial process.

The required studies and documentation depend on the product, development stage, applicable pharmacopoeia, and regulatory requirements.

A seal coat should not be introduced or removed from an established commercial formulation solely on the basis of a general recommendation. The impact on product quality and regulatory commitments must first be assessed.

Conclusion

Film seal coating can be a valuable formulation strategy before enteric coating, particularly when the tablet core presents compatibility, migration, interfacial, adhesion, or processing challenges.

Its primary role is to provide an optional intermediate layer that may improve the interaction between the tablet core and the functional enteric coating.

However, film seal coating is not universally mandatory before enteric coating. The correct approach is to evaluate the core composition, polymer compatibility, manufacturing process, dissolution performance, and stability requirements before deciding whether an additional layer is necessary.

In pharmaceutical manufacturing, the objective is not simply to add more coating layers. It is to develop a robust, reproducible, and scientifically justified coating system that consistently meets the intended quality and performance requirements.

References

Zaid AN. A Comprehensive Review on Pharmaceutical Film Coating: Past, Present, and Future. Drug Design, Development and Therapy. 2020;14:4613–4623. Read the review.
Pharmaceutical Application of Tablet Film Coating. Pharmaceutics. 2020;12(9):853. Read the review.
Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice. Chapter on general characteristics of the pharmaceutical coating process, including seal/barrier coating.
Crotts G, Sheth A, Twist J, Ghebre-Sellassie I. Development of an enteric coating formulation and process for tablets primarily composed of a highly water-soluble, organic acid. European Journal of Pharmaceutics and Biopharmaceutics. 2001;51(1):71–76. Read the study.
United States Pharmacopeia (USP). Disintegration: Procedure and Criteria for Delayed-Release Tablets and Capsules. Read the compendial guidance.
World Health Organization. Guidelines on pharmaceutical development and quality requirements for modified-release products. Read the WHO guidance.