List of Excipients in Branded Drug ASPIRIN AND OMEPRAZOLE DELAYED-RELEASE TAB

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Innovida Phamaceutique Corporation	ASPIRIN AND OMEPRAZOLE DELAYED-RELEASE TAB	aspirin and omeprazole	71800-014	CARNAUBA WAX	2033-01-02
Innovida Phamaceutique Corporation	ASPIRIN AND OMEPRAZOLE DELAYED-RELEASE TAB	aspirin and omeprazole	71800-014	CELLULOSE, MICROCRYSTALLINE	2033-01-02
Innovida Phamaceutique Corporation	ASPIRIN AND OMEPRAZOLE DELAYED-RELEASE TAB	aspirin and omeprazole	71800-014	FD&C BLUE NO. 2	2033-01-02
Innovida Phamaceutique Corporation	ASPIRIN AND OMEPRAZOLE DELAYED-RELEASE TAB	aspirin and omeprazole	71800-014	FERRIC OXIDE YELLOW	2033-01-02

Aspirin and Omeprazole Delayed-Release Tablets: Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: August 19, 2026

Aspirin and omeprazole delayed-release tablets, marketed in the United States as Yosprala, combine immediate-release aspirin with delayed-release omeprazole in a single oral dosage form. The product is designed for patients who require aspirin for secondary cardiovascular prevention and who also need omeprazole to reduce the risk of aspirin-associated gastric ulcers. Its commercial value depends on dose-specific prescribing, formulation complexity, regulatory substitution, and the ability to reproduce the dual-release profile.

The principal opportunity is a generic or licensed product that matches the reference product's aspirin release, omeprazole enteric protection, stability, tablet architecture, and labeling. The principal technical barrier is preventing aspirin and omeprazole from interacting during storage while maintaining reliable separation of their release profiles.

What is aspirin and omeprazole delayed-release tablets?

Yosprala contains aspirin and omeprazole in a fixed-dose combination tablet. The FDA-approved strengths are:

Strength	Aspirin	Omeprazole	Intended use
Low dose	81 mg	40 mg	Secondary prevention of cardiovascular and cerebrovascular events in patients requiring gastric protection
High dose	325 mg	40 mg	Same clinical setting where higher-dose aspirin is prescribed

Aspirin is released rapidly to provide antiplatelet activity. Omeprazole is delayed-release because it is acid-labile and must pass through the stomach before dissolution in the higher-pH environment of the small intestine. The product is therefore a combination of two different release systems in one tablet rather than a conventional immediate-release fixed-dose combination.[1]

The FDA indication is limited. Yosprala is not a general-purpose aspirin product, an over-the-counter gastrointestinal-protection product, or a substitute for independently titrated aspirin and proton-pump inhibitor therapy.[1]

How does the Yosprala formulation work?

The formulation separates the two active pharmaceutical ingredients through physical and functional design.

Aspirin release

The aspirin component is intended to dissolve promptly after oral administration. The relevant formulation requirements include:

• Rapid disintegration or dissolution of the aspirin portion
• Protection against premature interaction with omeprazole
• Control of aspirin degradation to salicylic acid and acetic acid
• Uniformity across the 81-mg and 325-mg strengths

Aspirin is moisture-sensitive and hydrolytically unstable. Moisture ingress can reduce assay, increase degradation products, alter tablet hardness, and create odor or packaging problems. Excipient selection therefore must support low water activity and robust moisture protection.

Omeprazole delayed release

Omeprazole is typically delivered through enteric-coated particles, pellets, granules, or a protected subunit embedded in the tablet. A functional design generally requires:

1. An omeprazole-containing core.
2. An alkaline or protective separation layer.
3. An enteric polymer layer.
4. A tablet structure that prevents damage to the delayed-release particles during compression and storage.

The enteric system must resist dissolution in gastric fluid and release omeprazole at intestinal pH. Common enteric-polymer families include methacrylic acid copolymers and cellulose-based phthalate or acetate phthalate systems. The selected polymer, plasticizer, coating weight, pore structure, and curing conditions determine dissolution performance.

What excipients are used in aspirin and omeprazole delayed-release tablets?

The FDA prescribing information identifies inactive ingredients for the commercial product, while the complete manufacturing formula and supplier grades are generally controlled by the sponsor. Publicly identified excipient categories include:

Excipient function	Likely or disclosed role
Diluent	Lactose, microcrystalline cellulose, or another compressible filler
Binder	Supports granule or tablet strength
Disintegrant	Promotes breakup of the aspirin-containing tablet matrix
Glidant	Improves powder flow during compression
Lubricant	Reduces sticking and ejection force
Alkalinizing or protective agent	Protects omeprazole from acidic and reactive environments
Enteric polymer	Prevents omeprazole release in the stomach
Plasticizer	Improves flexibility of the enteric film
Anti-tacking agent	Prevents coating-particle adhesion
Opacifier or colorant	Supports product identification and light protection

Representative excipient families used in comparable formulations include microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, hypromellose, methacrylic acid copolymers, triethyl citrate, talc, and polysorbates. The exact excipient list and quantity should be taken from the current FDA label and the applicable chemistry, manufacturing, and controls record rather than inferred from comparable proton-pump inhibitor products.[1]

Why alkaline excipients matter

Omeprazole degrades rapidly under acidic conditions. An alkaline microenvironment can improve stability, but excessive alkalinity can create compatibility problems with aspirin or alter the dissolution behavior of the enteric system. Formulators must balance:

• Omeprazole stabilization
• Aspirin hydrolysis control
• Tablet hardness
• Enteric-coating integrity
• Dissolution reproducibility
• Long-term impurity growth

This balance creates an opportunity for proprietary excipient systems, especially where the formulation uses a multilayer tablet, coated pellets, or a specialized barrier layer.

Why lubricant selection is commercially important

Magnesium stearate is widely used in tableting but can adversely affect wetting and dissolution when over-lubrication occurs. A formulation containing coated omeprazole particles must also avoid excessive shear and compression force. Lubricant concentration, blending time, particle-size distribution, and compression speed can materially affect delayed-release performance.

Alternative lubricant systems, including sodium stearyl fumarate or lower-level magnesium stearate, may support a differentiated manufacturing process. These changes require comparative dissolution, stability, and bioequivalence evidence.

What formulation patents protect aspirin and omeprazole tablets?

The relevant intellectual-property estate is centered on combination composition claims, dosage-form architecture, and methods of reducing gastrointestinal injury associated with aspirin therapy. U.S. patent protection for Yosprala has included patents assigned to or associated with the product's development and commercialization chain, including U.S. Patent Nos. 8,858,996 and 9,480,663.[2][3]

The commercial scope of these patents may cover:

• A tablet containing aspirin and omeprazole
• Immediate-release aspirin combined with delayed-release omeprazole
• Specific dose combinations
• Physical separation of the active ingredients
• Enteric-coated omeprazole particles
• Use of the combination to reduce aspirin-associated gastrointestinal injury
• Particular manufacturing or compression configurations

Patent claims must be reviewed claim by claim. A formulation that changes the enteric polymer, particle architecture, tablet layering, or excipient system may avoid some composition claims while remaining exposed to method-of-use or combination claims.

What patent claims are most difficult to design around?

The highest-risk claims are broad claims that cover the functional combination rather than a narrow supplier-specific formulation. A generic developer faces greater exposure where the reference product's claims recite:

• Both active ingredients in a single dosage form
• A defined aspirin-to-omeprazole dose relationship
• Aspirin release before omeprazole release
• Omeprazole protection in gastric fluid
• A therapeutic method involving patients receiving chronic aspirin

A narrow coating-composition claim is easier to design around than a claim directed to the overall dual-release concept. The strength of the estate therefore depends on claim breadth, prosecution history, terminal disclaimers, patent-term adjustments, and the status of Orange Book listings.

What is the Orange Book status of aspirin and omeprazole delayed-release tablets?

The FDA Orange Book identifies approved products, reference-listed-drug status, therapeutic-equivalence information, and listed patents where applicable. Yosprala is an NDA product rather than an ordinary unbranded aspirin or omeprazole product. Its regulatory relevance includes:

• Reference product status for an ANDA applicant
• Patent certifications under Section 505(j)
• Possible Paragraph IV challenges
• Potential 30-month litigation stays
• Patent listing and delisting disputes
• Product-specific labeling requirements

The Orange Book must be checked for the current patent list and expiration dates because patent listings, corrections, and regulatory determinations can change. A commercial launch analysis should not rely solely on the earliest patent priority date or a public patent-family database.[4]

When does aspirin and omeprazole lose exclusivity?

The product's commercial exclusivity has several layers:

Exclusivity layer	Commercial effect
FDA approval exclusivity	Restricts certain abbreviated applications for the statutory period
Listed patents	May delay or block commercial generic launch
Pediatric exclusivity	Can add six months where granted
Regulatory exclusivity for the combination	Depends on the original approval pathway and applicable FDA determination
Patent litigation	Can delay approval or create launch-risk costs
Formulation know-how	Can remain commercially relevant after formal patent expiry

Yosprala was approved by the FDA in 2016.[1] The key commercial question is not simply the expiration date of a single patent. It is whether a generic applicant can obtain approval, resolve Paragraph IV litigation, and launch without infringing enforceable claims.

Patent expiration is determined by the applicable patent term, patent-term adjustment, terminal disclaimers, pediatric extensions, and any relevant litigation outcome. The oldest listed patent is not always the final barrier to entry.

Which companies are challenging aspirin and omeprazole delayed-release tablets?

Generic competition would most likely arise from companies with established capabilities in:

• Complex oral solid-dose development
• Enteric-coated multiparticulates
• Proton-pump inhibitor formulations
• ANDA litigation
• High-volume aspirin manufacturing
• Moisture-controlled packaging

Potential participants include large generic manufacturers and specialty companies with experience in delayed-release omeprazole products. A company does not need to reproduce the branded excipient system exactly. It must demonstrate pharmaceutical equivalence and bioequivalence while satisfying applicable quality and performance requirements.

Publicly available information does not establish that a specific challenger has obtained final FDA approval for an AB-rated generic of Yosprala. A Paragraph IV certification, tentative approval, or litigation filing should be distinguished from commercial approval and actual market entry.

What Paragraph IV risks exist for Yosprala?

A Paragraph IV applicant could assert that listed patents are invalid, unenforceable, or not infringed. The principal possible arguments include:

• Lack of novelty or obviousness over aspirin-proton-pump inhibitor combinations
• Written-description or enablement defects
• Non-infringement through a different particle or coating architecture
• Non-infringement through separate tablets packaged together rather than a single tablet
• Invalidity based on prior art involving enteric-coated omeprazole and aspirin
• Patent-listing challenges involving method-of-use scope

The branded sponsor could respond with an infringement action, triggering the statutory stay associated with a qualifying Paragraph IV notice. The timing of litigation matters because a generic may receive tentative approval before it can lawfully launch.

What commercial opportunities exist in excipients?

The largest excipient opportunities are tied to stability, controlled release, and manufacturing yield rather than basic tablet fillers.

Enteric-coating systems

Excipient suppliers can offer prequalified systems using methacrylic acid copolymers, plasticizers, anti-tacking agents, and optimized coating protocols. A supplier that reduces coating weight while preserving acid resistance can lower tablet mass and improve manufacturing economics.

Protective separation layers

A proprietary barrier layer between aspirin and omeprazole may reduce degradation and extend shelf life. Opportunities include:

• Alkaline polymer matrices
• Low-moisture protective coatings
• Film barriers with controlled permeability
• Excipient combinations that reduce direct active-to-active contact

Moisture-control systems

Packaging and excipient strategy are closely linked. Commercial options include:

• High-barrier blister films
• Desiccant-containing bottles
• Low-moisture excipient grades
• Oxygen and humidity scavengers
• Improved tablet-film coatings

A formulation that achieves equivalent stability with less expensive packaging can produce meaningful cost savings.

Compression-protective multiparticulates

Omeprazole pellets can fracture during compression. Excipients that improve pellet elasticity, cushion particles, or reduce interparticle shear may improve yield and dissolution consistency. This is a practical area for platform licensing and contract-development partnerships.

Pediatric and geriatric dosage forms

The approved product is a tablet, but age-specific opportunities may include:

• Sprinkle-capable multiparticulates
• Sachets
• Orally disintegrating tablets
• Lower-dose aspirin combinations
• Alternative packaging for adherence-sensitive patients

These products would require separate regulatory strategies and may raise distinct patent and exclusivity questions.

How does Yosprala compare with separate aspirin and omeprazole products?

Factor	Fixed-dose aspirin/omeprazole tablet	Separate aspirin and omeprazole
Dosing convenience	One dosage form	Two products
Dose flexibility	Limited to marketed strengths	Greater titration flexibility
Adherence	Potentially improved	More opportunities for missed doses
Formulation complexity	High	Lower for each individual product
Generic substitution	Product-specific	Broad product availability
Development risk	Dual-release and compatibility risk	Established individual dosage forms
Commercial differentiation	Combination convenience and gastric protection	Lower product-specific differentiation

The fixed-dose product has a clinical and commercial rationale where aspirin use is chronic and gastrointestinal protection is part of the treatment plan. Its disadvantage is reduced dosing flexibility and higher manufacturing complexity.

What biosimilar risk exists for aspirin and omeprazole tablets?

There is no biosimilar pathway for this product. Aspirin and omeprazole are small-molecule active ingredients. Competitive entry would proceed primarily through the ANDA pathway, 505(b)(2) applications, or, in some cases, a new NDA for a differentiated formulation.

A 505(b)(2) product could pursue a modified dose, delivery system, or formulation with reliance on FDA findings for one or both active ingredients. This route may support commercial differentiation but could face patent certification and exclusivity issues.

What manufacturing and IP barriers affect generic entry?

The main manufacturing barriers are:

• Omeprazole sensitivity to acid, moisture, heat, and light
• Aspirin hydrolysis
• Interaction between the two active ingredients
• Damage to enteric-coated particles during compression
• Batch-to-batch dissolution variability
• Stability failures at accelerated conditions
• Need for specialized coating and compression equipment
• Packaging requirements that protect against moisture

The main IP barriers are:

• Combination-composition patents
• Delayed-release architecture claims
• Method-of-use patents
• Manufacturing-process claims
• Orange Book patent certifications
• Potential litigation before launch

A generic applicant may reduce risk by using a distinct tablet architecture, such as a bilayer tablet, coated mini-tablets, or a capsule-in-tablet configuration. Each alternative introduces new scale-up and bioequivalence risks.

What is the commercial outlook for aspirin and omeprazole delayed-release tablets?

The product occupies a narrow but defensible niche. Revenue depends on the number of patients who need both chronic aspirin and gastric protection, physician willingness to prescribe a branded combination, payer coverage, and the price gap versus separate generic products.

Commercial opportunities include:

1. An AB-rated generic with lower manufacturing cost.
2. A licensed product using an established enteric-coating platform.
3. A lower-cost formulation with improved moisture stability.
4. A 505(b)(2) product with new dosing or delivery characteristics.
5. Regional licensing in markets where fixed-dose cardiovascular combinations are accepted.
6. Contract manufacturing of coated omeprazole particles and finished tablets.
7. Excipient licensing for barrier layers and compression protection.

A generic launch would likely pressure net pricing rapidly because both aspirin and omeprazole are widely available as low-cost individual products. The combination's value proposition is adherence and convenience, not ingredient scarcity.

Key Takeaways

• Aspirin and omeprazole delayed-release tablets combine immediate-release aspirin with enteric-protected omeprazole.
• The core technical challenge is maintaining omeprazole stability without compromising aspirin stability or release.
• Excipient value is concentrated in enteric coatings, alkaline protection, barrier layers, moisture control, and compression-protective systems.
• Yosprala's patent estate includes combination and formulation-related protection, with U.S. Patent Nos. 8,858,996 and 9,480,663 among the identified patents.[2][3]
• Generic entry would use the ANDA pathway and could involve Paragraph IV litigation.
• Biosimilar competition is not relevant because both active ingredients are small molecules.
• The most credible commercial opportunities are generic development, formulation licensing, specialized excipients, and improved delivery systems.
• Separate generic aspirin and omeprazole products remain the principal price competitor.

FAQs

Can aspirin and omeprazole be combined in a standard immediate-release tablet?

No. Omeprazole requires acid protection. An immediate-release tablet that exposes omeprazole to gastric acid would not reproduce the intended delayed-release performance.

Why is omeprazole usually formulated with an enteric coating?

Omeprazole is acid-labile. The enteric coating prevents release in the stomach and enables dissolution after the dosage form reaches the higher-pH environment of the intestine.

Is a bilayer aspirin and omeprazole tablet automatically non-infringing?

No. A different physical architecture may avoid some formulation claims, but it could still fall within broader combination, method-of-use, or functional claims.

Can an excipient supplier patent an omeprazole barrier layer?

Yes. A supplier may seek patent protection for a defined excipient composition, coating sequence, particle structure, manufacturing process, or stability improvement. Enforceability depends on claim scope and patent validity.

Would a separate aspirin tablet plus an omeprazole capsule compete directly with Yosprala?

Yes. Separate generic products provide a lower-cost alternative, although they do not provide the same single-tablet dosing convenience or identical release architecture.

References

1. U.S. Food and Drug Administration. (2016). Yosprala: Aspirin and omeprazole delayed-release tablets, prescribing information. FDA Drugs@FDA.

2. U.S. Patent No. 8,858,996. (2014). Pharmaceutical compositions comprising aspirin and a proton pump inhibitor. United States Patent and Trademark Office.

3. U.S. Patent No. 9,480,663. (2016). Pharmaceutical compositions comprising aspirin and a proton pump inhibitor. United States Patent and Trademark Office.

4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.