List of Excipients in Branded Drug YOSPRALA

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Genus Lifesciences Inc	YOSPRALA	aspirin and omeprazole	64950-424	CARNAUBA WAX	2033-01-02
Genus Lifesciences Inc	YOSPRALA	aspirin and omeprazole	64950-424	CELLULOSE, MICROCRYSTALLINE	2033-01-02
Genus Lifesciences Inc	YOSPRALA	aspirin and omeprazole	64950-424	FD&C BLUE NO. 2	2033-01-02
Genus Lifesciences Inc	YOSPRALA	aspirin and omeprazole	64950-424	FERRIC OXIDE YELLOW	2033-01-02
Genus Lifesciences Inc	YOSPRALA	aspirin and omeprazole	64950-424	GLYCERYL MONOSTEARATE	2033-01-02

Yosprala Excipient Strategy and Commercial Opportunities

Last updated: August 13, 2026

Yosprala is a fixed-dose, two-strength combination of aspirin and delayed-release omeprazole designed to reduce gastrointestinal risk associated with chronic aspirin therapy. Its commercial differentiation depends on the formulation architecture, not the active ingredients. The principal opportunities are generic or 505(b)(2) development, lactose-free and smaller-tablet reformulation, manufacturing-cost reduction, improved stability, and alternative gastroprotection strategies.

Yosprala received FDA approval in September 2016 under NDA 208673. The product is available as 81 mg aspirin/40 mg omeprazole and 325 mg aspirin/40 mg omeprazole delayed-release tablets.[1]

What is Yosprala and how does its formulation work?

Yosprala combines immediate-release aspirin with delayed-release omeprazole in a single tablet. Aspirin provides antiplatelet activity, while omeprazole reduces gastric acid secretion and is intended to reduce the risk of aspirin-associated gastric ulcers in selected patients.

The product’s formulation has three commercial objectives:

1. Deliver aspirin without delaying its antiplatelet effect.
2. Protect omeprazole from degradation in the acidic stomach environment.
3. Provide a single-tablet alternative to separately prescribed aspirin and proton-pump inhibitor therapy.

The two active strengths are:

Product	Aspirin dose	Omeprazole dose	Dosage form
Yosprala 81/40	81 mg	40 mg	Delayed-release tablet
Yosprala 325/40	325 mg	40 mg	Delayed-release tablet

The product is intended for patients who require aspirin for secondary cardiovascular prevention and are considered appropriate candidates for concomitant omeprazole therapy. It is not positioned as a general substitute for low-dose aspirin in all cardiovascular patients.[1]

What excipients are used in Yosprala?

Public FDA labeling identifies a conventional oral solid-dose excipient system containing fillers, binders, lubricants, coating materials and acid-protection components. The inactive ingredients listed in FDA labeling include lactose monohydrate, hypromellose, glyceryl behenate, magnesium stearate, povidone, talc, titanium dioxide, polyethylene glycol, methacrylic acid copolymer, sodium lauryl sulfate and other processing excipients.[1]

The excipients can be grouped by function:

Excipient function	Representative materials	Commercial purpose
Diluent or filler	Lactose monohydrate	Tablet mass, compressibility and content uniformity
Binder	Povidone, hypromellose	Granule and tablet strength
Lubricant	Magnesium stearate, glyceryl behenate	Ejection and manufacturing efficiency
Film former	Hypromellose	Functional and protective coating
Enteric polymer	Methacrylic acid copolymer	Delayed release and gastric protection
Plasticizer	Polyethylene glycol	Coating flexibility
Opacifier or pigment	Titanium dioxide, talc	Appearance and light protection
Surfactant	Sodium lauryl sulfate	Wetting and dispersion
Processing aid	Colloidal silicon dioxide and related materials	Flow and handling

The precise role of each excipient depends on the manufacturing subunit. Yosprala’s technical challenge is the coexistence of aspirin and omeprazole, which have different stability and release requirements. Omeprazole is acid-labile, while aspirin can hydrolyze to salicylic acid in the presence of moisture. Moisture control, coating integrity, particle distribution and compression conditions are therefore central to product performance.

Which excipient attributes are most important for Yosprala?

Moisture control

Moisture is a high-priority formulation variable. It can accelerate aspirin hydrolysis and compromise omeprazole stability. Commercial developers should evaluate:

• Water activity and residual moisture in granules.
• Moisture permeability of the bottle or blister.
• Desiccant requirements.
• Coating weight gain and defect rate.
• Stability after opening and repeated patient handling.

A lower-cost excipient is commercially unattractive if it increases impurity formation or shortens shelf life. The strongest cost-reduction candidates are excipients with equivalent moisture performance, not simply lower unit prices.

Enteric-coating performance

The delayed-release component requires reproducible resistance to gastric acid and release at intestinal pH. Critical variables include:

• Polymer grade and molecular weight.
• Coating thickness.
• Plasticizer concentration.
• Spray rate and inlet temperature.
• Tablet surface roughness.
• Curing conditions.
• Mechanical damage during packaging.

An enteric system that passes dissolution at release but fails under accelerated stability conditions presents a material regulatory and recall risk.

Compression and segregation

A fixed-dose tablet containing two pharmacologically distinct components must maintain dose uniformity across the manufacturing run. Differences in particle size, density and flow can cause segregation. Developers should characterize:

• Aspirin particle-size distribution.
• Omeprazole particle-size distribution.
• Blend uniformity.
• Granule density.
• Tablet hardness and friability.
• Compression force.
• Weight variation.
• Content uniformity for both actives.

The 81/40 and 325/40 strengths also create a ratio challenge. The omeprazole dose remains constant while aspirin changes fourfold. A platform process that works for one strength may require different granulation or compression parameters for the other.

Lubrication

Over-lubrication can reduce tablet tensile strength and alter dissolution. Magnesium stearate concentration, mixing time and shear should be treated as critical process variables. Glyceryl behenate may offer useful lubrication and hydrophobicity, but its impact on wetting and release must be measured against the selected coating system.

Lactose content

Lactose is a potential commercial limitation for patients with lactose intolerance, although lactose intolerance is not equivalent to clinically significant milk-protein allergy. A lactose-free version could provide a differentiated product, particularly in hospital formularies, specialty pharmacies and markets with high demand for excipient-reduced formulations.

Replacing lactose is not a simple substitution. Candidate fillers such as microcrystalline cellulose, mannitol, dibasic calcium phosphate or selected co-processed excipients can change:

• Tablet size.
• Disintegration.
• Compression force.
• Moisture uptake.
• Granule flow.
• Bioequivalence risk.
• Manufacturing throughput.

A lactose-free version is most attractive if it also reduces tablet size or improves stability.

What formulations are protected by Yosprala’s product design?

Yosprala’s core commercial value lies in a coordinated formulation that combines aspirin with delayed-release omeprazole. The relevant protection is likely to involve composition, dosage form, release profile, manufacturing process and therapeutic use rather than the old active ingredients themselves.

The active ingredients are established drugs. Aspirin and omeprazole have long histories of generic use, and their basic compound patents have expired. Any remaining differentiation must therefore arise from the combination and delivery system.

Potential protected features include:

• A single dosage form containing aspirin and omeprazole.
• Immediate-release aspirin with delayed-release omeprazole.
• Specific aspirin-to-omeprazole ratios.
• Enteric protection of omeprazole.
• Stability controls for co-formulation.
• Pharmaceutical compositions for reducing aspirin-associated gastric injury.
• Manufacturing processes that preserve aspirin and omeprazole potency.
• Specific dissolution or release characteristics.

The scope and remaining term of each patent must be confirmed against the current USPTO, FDA Orange Book and applicable national registers. Patent family members can differ materially by jurisdiction, and an expired composition patent does not eliminate potential exposure under process or method-of-use claims.

When does Yosprala lose exclusivity?

Yosprala’s FDA approval occurred on September 15, 2016.[1] The active ingredients do not provide new chemical entity exclusivity because aspirin and omeprazole were previously approved. The principal regulatory exclusivity associated with the product was therefore likely the three-year exclusivity period applicable to certain new clinical investigations supporting approval of a new formulation or combination.[2]

That exclusivity would generally have expired in 2019, subject to the specific FDA determination and scope of the protected conditions of approval. Patent protection may extend beyond regulatory exclusivity.

The relevant exclusivity framework is:

Protection	Likely relevance to Yosprala	Commercial effect
NCE exclusivity	Not applicable to established aspirin and omeprazole	Does not block ANDA filing
Three-year exclusivity	Potentially applicable to the approved combination or formulation	May restrict approval of certain ANDAs relying on the protected clinical investigation
Orphan exclusivity	Not applicable	No orphan block expected
Patent protection	Combination, formulation, method or process claims	May delay or complicate generic launch
Pediatric exclusivity	Depends on FDA grant	Could add six months to qualifying exclusivity

The product’s true generic-entry date depends on current listed patents, statutory certifications, litigation and settlement terms. A single expiration date should not be used without reviewing the Orange Book listing and patent litigation history.

What is the Orange Book status of Yosprala?

Yosprala is an NDA product and may have FDA Orange Book-listed patents covering its formulation or approved use. Orange Book records are the starting point for assessing ANDA certification pathways under Hatch-Waxman.[3]

A potential generic applicant would normally evaluate:

• Paragraph I certification if no patent information is listed.
• Paragraph II certification if the listed patent has expired.
• Paragraph III certification if the applicant accepts approval after patent expiry.
• Paragraph IV certification if the applicant asserts that the patent is invalid, unenforceable or not infringed.
• A section viii statement for a method-of-use patent where the applicant carves out the protected use.

Because the active ingredients are generic, the principal ANDA risk is formulation equivalence. FDA approval would require the applicant to demonstrate pharmaceutical equivalence and bioequivalence, including the relevant aspirin and omeprazole release characteristics.[4]

Are Paragraph IV challenges likely for Yosprala?

Paragraph IV activity is commercially plausible because the product contains old active ingredients in a differentiated fixed-dose formulation. A generic company could challenge formulation or method patents while using non-infringing excipients and a different coating system.

The most likely challenge theories would involve:

• Lack of novelty in combining aspirin and omeprazole.
• Obviousness based on prior aspirin/PPI combination products.
• Non-infringement through an alternative enteric polymer or process.
• Invalidity based on inadequate written description or enablement.
• Narrow construction of release-profile claims.
• Expired or improperly listed method-of-use claims.

A Paragraph IV filing would trigger the statutory 45-day period for the NDA holder to sue. A timely patent suit can generate a 30-month stay of ANDA approval, subject to statutory exceptions and court action.[5]

What generic entry risks exist for Yosprala?

Generic entry risk is moderate to high at the active-ingredient level and more complex at the formulation level.

Risk category	Assessment	Reason
Active-ingredient competition	High	Aspirin and omeprazole are widely available generic products
Fixed-dose combination challenge	Moderate	Requires matching both components in one dosage form
Enteric-release replication	Moderate to high	Coating and dissolution performance are technically sensitive
Patent challenge	Moderate	Combination and formulation claims may be vulnerable to validity attacks
Manufacturing scale-up	Moderate	Moisture and segregation create process-development risk
Substitution risk	Moderate	Separate aspirin plus omeprazole is a practical alternative
Authorized generic risk	Unknown	Depends on sponsor strategy and commercial agreements

A generic does not necessarily need to copy every inactive ingredient. FDA generally permits differences in inactive ingredients if the product meets applicable safety, quality, equivalence and labeling requirements.[4] This creates room for design-around strategies based on lactose-free fillers, alternative enteric polymers or different coating processes.

What excipient strategies create commercial opportunities?

Lactose-free Yosprala

A lactose-free tablet could target patients and prescribers seeking reduced excipient burden. The most promising development path would use a directly compressible filler system with low moisture uptake and sufficient mechanical strength.

Commercial advantages could include:

• Differentiation from the reference product.
• Broader use in patients avoiding lactose-containing medicines.
• Potential institutional formulary interest.
• Reduced dependence on lactose supply.
• Opportunity for a line extension or 505(b)(2) product.

The main risks are increased tablet size, altered disintegration and a need for new stability data.

Smaller-tablet formulation

Yosprala tablets contain a relatively high omeprazole dose compared with low-dose aspirin products. A multiparticulate or bilayer architecture could reduce tablet size or improve swallowability.

Potential approaches include:

• Higher-density granulation.
• More efficient filler selection.
• Coated omeprazole pellets compressed into a tablet.
• Bilayer compression.
• Mini-tablets within a capsule.
• Capsule-based multiparticulates.

A smaller dosage form could improve adherence in older cardiovascular patients, although any change in release architecture could increase regulatory complexity.

Improved moisture-barrier packaging

Packaging is an underused commercial opportunity. A developer could preserve the same tablet formulation while improving shelf life through:

• High-barrier aluminum-aluminum blistering.
• Unit-dose packaging.
• Desiccant-equipped bottles.
• Lower-permeability polymer containers.
• Humidity-resistant closures.

Packaging changes may be less disruptive than excipient substitution. They can also reduce aspirin degradation and protect omeprazole during distribution in hot and humid climates.

Excipient simplification

A reduced-excipient product could eliminate unnecessary colorants, reduce surfactant content or use a single multifunctional coating system. This may appeal to hospital buyers and patients who prefer simpler formulations.

The value is greatest when simplification produces measurable benefits:

• Lower manufacturing cost.
• Fewer supplier dependencies.
• Lower extractables and leachables risk.
• Improved regulatory manageability.
• Better patient acceptance.

A simplified formulation without a clinical or operational advantage may not justify development expenditure.

Pediatric or swallowing-friendly presentations

Yosprala is principally associated with adult cardiovascular prevention. A pediatric opportunity is limited because chronic aspirin use is restricted in children and the product’s approved use is not a general pediatric indication. An orally disintegrating or sprinkle formulation would therefore require a clear clinical niche and substantial regulatory justification.

How does Yosprala compare with separate aspirin and omeprazole?

Criterion	Yosprala	Separate aspirin plus omeprazole
Pill burden	One tablet	Two products
Dose flexibility	Limited to marketed strengths	High
Adherence	Potentially improved	More administration steps
Generic availability	Combination-specific	Broad
Formulation complexity	High	Lower for each individual product
Cost pressure	Combination product may carry a premium	Usually lower
Substitution risk	Meaningful	Strong
Pharmacy flexibility	Lower	Higher

Yosprala’s commercial proposition is convenience and coordinated delivery. Its weakness is limited dosing flexibility and the availability of inexpensive generic alternatives. A successful follow-on product must therefore demonstrate a clear advantage in price, tolerability, pill size, stability, packaging or adherence.

What patent litigation affects Yosprala?

Publicly available product information supports analysis of the FDA approval and formulation, but a complete current litigation assessment requires verified docket review across federal courts, the Federal Circuit and applicable settlement records. Patent litigation risk should be assessed against:

• Orange Book-listed patents.
• ANDA filing dates.
• Paragraph IV notices.
• District court complaints.
• Patent trial outcomes.
• Settlement agreements.
• Authorized-generic provisions.
• Launch dates tied to patent expiry.

Where a patent settlement exists, its economic terms can materially alter launch timing. A settlement may permit an early generic launch before the nominal patent expiry, provide a license for an authorized generic, or restrict the generic’s dosage strengths or distribution channel.

What FDA regulatory pathway would a follow-on Yosprala use?

A conventional generic would generally seek approval under section 505(j) through an ANDA. The applicant would need to demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug.

A 505(b)(2) application may be more suitable where the sponsor proposes:

• A new dosage form.
• A substantially different release system.
• A new strength.
• A new indication.
• A clinically meaningful formulation change.
• A different administration method.

A 505(b)(2) product can support differentiation but may face reliance-related patent certifications and additional clinical or pharmacokinetic requirements. The commercial choice is therefore between a lower-cost ANDA replication strategy and a higher-value differentiated formulation strategy.

How strong is the Yosprala patent estate?

The estate’s strength depends on claim scope, expiration, prosecution history and prior art. The broadest concept, aspirin plus omeprazole in one product, is likely more vulnerable than narrow claims directed to:

• Specific release sequencing.
• Defined dissolution profiles.
• Coating architecture.
• Stability under specified conditions.
• Manufacturing controls.
• Therapeutic use in a defined patient population.

A strong formulation patent should connect the claimed excipients or process to a measurable technical result, such as improved stability, reliable delayed release or reduced gastric injury. Claims that merely recite known excipients without demonstrated functional distinction face greater validity risk.

What revenue exposure does Yosprala create?

Yosprala revenue is exposed to three forms of substitution:

1. Generic aspirin and generic omeprazole prescribed separately.
2. Other aspirin/PPI combinations.
3. Cardiovascular prevention regimens that do not include chronic aspirin.

The commercial value is therefore concentrated in patients and prescribers who value single-tablet administration or gastrointestinal risk management. Revenue protection depends less on exclusivity over aspirin and omeprazole than on retaining the combination’s adherence and convenience advantages.

Public FDA approval materials do not establish a reliable current revenue figure. Revenue analysis should use verified sponsor disclosures, prescription data and payer formulary information rather than extrapolating from approval status.

Key Takeaways

• Yosprala is a fixed-dose combination of aspirin and delayed-release omeprazole approved in 2016 under NDA 208673.
• Its core formulation challenge is maintaining aspirin stability while protecting omeprazole from gastric acid.
• The principal excipient opportunities are lactose-free substitution, moisture-barrier packaging, smaller tablets, excipient simplification and alternative multiparticulate systems.
• Aspirin and omeprazole are established generic ingredients, so commercial differentiation depends on formulation, packaging, adherence and regulatory strategy.
• An ANDA is the likely pathway for a close generic equivalent; a 505(b)(2) application is more appropriate for a materially differentiated dosage form.
• Paragraph IV risk is concentrated in combination, formulation, process and method-of-use patents.
• Separate generic aspirin plus omeprazole remains the main commercial substitute.
• Current Orange Book listings, patent expiration dates, litigation and settlement terms must control any launch-timing or valuation conclusion.

FAQs

Can a generic Yosprala use different excipients?

Yes. A generic applicant can generally use different inactive ingredients if the product satisfies FDA safety, quality, pharmaceutical-equivalence and bioequivalence requirements. The alternative excipients cannot compromise release, stability or performance.

Is lactose-free Yosprala likely to receive separate patent protection?

It may, but lactose removal alone is unlikely to create strong patent protection. Patentability would be stronger if the lactose-free formulation produces an unexpected technical result, such as improved stability, reduced tablet size or superior dissolution.

Could omeprazole be replaced with another proton-pump inhibitor?

Yes, but the resulting product would no longer be a direct Yosprala equivalent. It would likely require a separate regulatory strategy and could face different clinical, patent and bioequivalence requirements.

Does improved packaging avoid formulation patent infringement?

Not necessarily. Packaging changes may avoid process or stability claims in some cases, but they do not eliminate exposure to composition, dosage-form, release-profile or method-of-use patents.

What is the highest-value excipient opportunity for a Yosprala competitor?

A lactose-free, smaller and moisture-stable tablet has the strongest combined commercial rationale. It could address excipient preference, swallowability, shelf-life and manufacturing efficiency while preserving the single-tablet value proposition.

References

1. U.S. Food and Drug Administration. (2016). Yosprala (aspirin and omeprazole) delayed-release tablets: Prescribing information. NDA 208673.

2. U.S. Food and Drug Administration. (n.d.). New drug application exclusivity. FDA.

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

4. U.S. Food and Drug Administration. (2017). Guidance for industry: ANDAs for certain highly purified synthetic peptides. FDA.

5. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. §355(j).