List of Excipients in Branded Drug OXYCODONE AND ASPIRIN

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Generic Drugs Containing OXYCODONE AND ASPIRIN

Company	Ingredient	NDC	Excipient
Epic Pharma LLC	oxycodone and aspirin	42806-061	CELLULOSE, MICROCRYSTALLINE
Epic Pharma LLC	oxycodone and aspirin	42806-061	STARCH, CORN
Epic Pharma LLC	oxycodone and aspirin	42806-061	ZINC STEARATE
Physicians Total Care Inc	oxycodone and aspirin	54868-2094	CELLULOSE, MICROCRYSTALLINE

What are the Most Frequently-Used Excipients in OXYCODONE AND ASPIRIN?

# Of NDCs	Excipient
3	CELLULOSE, MICROCRYSTALLINE
1	D&C YELLOW NO. 10
1	SILICON DIOXIDE
3	STARCH, CORN

Oxycodone and Aspirin Excipient Strategy and Commercial Opportunities

Last updated: August 23, 2026

Oxycodone and aspirin is a mature opioid-analgesic combination with limited branded growth potential and greater opportunity in reformulation, abuse-deterrence, manufacturing efficiency, and controlled-distribution channels. The principal reference product is Percodan, containing oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 325 mg aspirin per tablet. The combination is subject to Schedule II opioid controls, aspirin-related gastrointestinal and bleeding risks, and intense FDA scrutiny of opioid labeling and abuse potential.[1-4]

What is the oxycodone and aspirin combination?

Oxycodone and aspirin combines a potent opioid analgesic with a nonsteroidal anti-inflammatory and antiplatelet drug.

Attribute	Oxycodone and aspirin
Active ingredients	Oxycodone hydrochloride and aspirin
Historical reference brand	Percodan
Typical tablet strength	Oxycodone HCl 4.8355 mg, equivalent to 4.5 mg oxycodone, plus aspirin 325 mg
Therapeutic category	Opioid analgesic combination
Controlled-substance status	Schedule II in the United States
Main indication	Short-term management of pain severe enough to require an opioid when alternatives are inadequate
Primary commercial substitutes	Oxycodone/acetaminophen, hydrocodone/acetaminophen, tramadol combinations, non-opioid multimodal regimens
Key safety constraints	Respiratory depression, dependence, misuse, overdose, gastrointestinal bleeding, renal injury, and aspirin hypersensitivity

The fixed combination is pharmacologically rational for some acute pain settings, but the aspirin component narrows the addressable population. Aspirin is unsuitable or clinically problematic for patients with active ulcer disease, bleeding risk, anticoagulant use, aspirin-sensitive asthma, renal impairment, or selected perioperative conditions.[1,2]

What patents protect oxycodone and aspirin products?

The principal commercial protection for oxycodone and aspirin has historically come from product approval, controlled-substance regulation, manufacturing know-how, and distribution controls rather than a durable modern patent estate.

The original Percodan product was approved decades ago. Any original compound, composition, or early formulation patents would generally have expired. Current commercial barriers therefore depend more heavily on:

• FDA approval and labeling;
• controlled-substance quotas and registration;
• manufacturing compliance;
• validated content uniformity for low-dose oxycodone;
• supply-chain security;
• opioid abuse-deterrence technology;
• customer qualification and institutional contracts.

A new entrant could seek protection for a differentiated formulation, but a basic immediate-release tablet containing oxycodone and aspirin would face a weak patent position unless it includes a novel formulation, manufacturing process, abuse-deterrent system, or clinically supported dosing advantage.

What formulation patents could protect an oxycodone and aspirin product?

Potentially protectable features include:

1. Abuse-deterrent matrix technology that limits crushing, extraction, snorting, or injection.
2. Modified-release delivery that controls oxycodone exposure while maintaining aspirin release.
3. Gastroprotective systems designed to reduce aspirin-related gastric irritation.
4. Multiparticulate or multilayer tablets that separate aspirin and oxycodone during manufacturing or dissolution.
5. Low-dust, high-hardness tablets for tamper resistance.
6. Taste-masked or orally disintegrating dosage forms, although opioid diversion concerns would complicate this route.
7. Manufacturing processes that improve oxycodone assay uniformity at low drug loading.
8. Packaging systems that support unit-dose control, serialization, and diversion monitoring.

A patent directed only to routine excipients, conventional compression, or standard disintegrants would likely have limited defensive value. Stronger claims would require comparative dissolution, tamper-resistance, stability, manufacturability, or clinical evidence.

When did oxycodone and aspirin lose exclusivity?

Oxycodone and aspirin has no meaningful remaining protection from the original Percodan exclusivity period. The reference product is a mature prescription product, and generic competition has historically been possible through abbreviated new drug application pathways where an approved reference product and applicable listing exist.

Protection category	Commercial position
Original product patents	Historically expired or commercially irrelevant
New chemical entity exclusivity	Expired
Original FDA marketing exclusivity	Expired
Basic immediate-release formulation protection	Weak or expired
Controlled-substance regulation	Remains active
Formulation-specific patents	May protect a new product if claims are valid and non-obvious
Abuse-deterrent technology	Potentially protectable through patents and regulatory differentiation
Trade secrets	Relevant for process controls, compression, coating, and supply-chain systems

The absence of meaningful original exclusivity does not eliminate market-entry barriers. Schedule II manufacturing, quota allocation, DEA compliance, pharmacovigilance, and retailer acceptance can delay or prevent commercial entry even where patent protection is limited.[3,4]

What is the FDA regulatory status of oxycodone and aspirin?

Oxycodone and aspirin is an FDA-approved combination product category represented historically by Percodan. The product is regulated as a prescription opioid and is subject to the Federal Food, Drug, and Cosmetic Act, the Controlled Substances Act, opioid labeling requirements, and postmarketing safety obligations.

The regulatory profile includes:

• Schedule II classification;
• no refills under federal controlled-substance rules;
• prescription and dispensing controls;
• boxed-warning opioid language;
• medication guide requirements;
• abuse, misuse, addiction, overdose, and death warnings;
• neonatal opioid withdrawal warnings where applicable;
• aspirin-related bleeding and gastrointestinal warnings;
• exposure restrictions for vulnerable populations.

An applicant developing a new product would need to determine whether it can rely on an existing reference product through an ANDA or whether formulation changes require a new 505(b)(2) application. A materially different release profile, abuse-deterrent design, gastroprotective mechanism, or clinical use could favor the 505(b)(2) route.

What is the Orange Book status of oxycodone and aspirin?

Orange Book analysis should distinguish between the reference product, discontinued products, and currently marketed generic presentations. A product may remain relevant as an FDA reference standard even when a particular labeled product is discontinued or has limited commercial availability.

For a prospective entrant, the key Orange Book questions are:

• Which oxycodone-and-aspirin reference-listed drugs remain identified?
• Is the selected reference product currently marketed?
• Are patents or regulatory exclusivity codes listed?
• Are there therapeutic-equivalence ratings for approved generic products?
• Does the dosage form match the proposed product?
• Are there withdrawal or discontinuation notations affecting ANDA reliance?

The Orange Book should be reviewed together with FDA’s discontinued-drug databases and current labeling records. Orange Book listing alone does not establish current market volume or a viable commercial opportunity.[5]

How should excipients be selected for oxycodone and aspirin tablets?

The optimal excipient system must balance low-dose oxycodone uniformity, aspirin stability, rapid release, tablet robustness, and abuse-deterrence objectives.

Core excipient functions

Function	Candidate excipient classes	Strategic purpose
Dilution	Microcrystalline cellulose, lactose, mannitol, dibasic calcium phosphate	Supports tablet weight and content uniformity
Binding	Povidone, copovidone, pregelatinized starch	Improves granule and tablet strength
Disintegration	Croscarmellose sodium, crospovidone, sodium starch glycolate	Promotes immediate release
Lubrication	Magnesium stearate, sodium stearyl fumarate	Supports ejection and processability
Glidancy	Colloidal silicon dioxide	Improves powder flow
Moisture control	Low-moisture excipient systems, protective packaging	Limits aspirin hydrolysis
Coating	Hypromellose, polyvinyl alcohol, titanium dioxide, approved colorants	Improves swallowability, identification, and handling
Gastroprotection	Enteric polymers or co-formulated protective systems	Could reduce gastric exposure but may alter product classification and clinical profile

A conventional immediate-release tablet would generally favor microcrystalline cellulose, a superdisintegrant, a low-level binder, colloidal silicon dioxide, and a lubricant. The formulation should avoid excipients or processing conditions that promote aspirin hydrolysis to salicylic acid.

Why aspirin stability is a central formulation issue

Aspirin is moisture-sensitive. Hydrolysis can increase salicylic acid levels and affect potency, impurity profiles, odor, and patient acceptability. The formulation and packaging program should therefore focus on:

• water activity;
• excipient moisture;
• granulation temperature;
• drying endpoint;
• compression heat;
• coating permeability;
• blister or bottle moisture transmission;
• long-term storage conditions.

Direct compression may reduce water exposure compared with aqueous wet granulation, but it requires strong powder-flow and content-uniformity control. Dry granulation can improve process robustness where direct compression is inadequate.

What abuse-deterrent formulation opportunities exist?

Abuse-deterrent design is the strongest potential differentiator for a new oxycodone-and-aspirin product, although aspirin adds technical complications.

Possible approaches include:

• high-hardness tablets that resist crushing;
• polymer matrices that form a viscous gel when exposed to water;
• chemical barriers to solvent extraction;
• multiparticulate systems that reduce dose dumping;
• physical and chemical barriers that limit injection suitability;
• packaging that reduces access to large quantities.

FDA evaluates abuse-deterrent products against specific routes of abuse and does not treat a formulation as abuse-deterrent merely because it is difficult to crush. Labeling claims require evidence under FDA’s abuse-deterrent guidance.[6]

Aspirin may complicate extraction-based abuse-deterrence because the formulation must prevent manipulation of oxycodone without compromising aspirin dissolution, stability, or dose uniformity. A matrix that substantially delays aspirin release could change the clinical profile and require additional pharmacokinetic and clinical evaluation.

What commercial opportunities exist for oxycodone and aspirin?

The broad mass-market opportunity is limited. The more credible opportunities are niche products with a clear technical or institutional advantage.

1. Generic immediate-release tablets

A standard generic product could compete on:

• supply reliability;
• contract pricing;
• hospital and wholesaler availability;
• packaging flexibility;
• low manufacturing cost;
• dual-source or secondary-source status.

Margins would likely be constrained by established opioid manufacturers, commodity tablet technology, purchasing-group pressure, and a declining preference for opioid combinations.

2. Abuse-deterrent product

An abuse-deterrent version could support a differentiated regulatory and commercial strategy. The opportunity depends on:

• evidence of meaningful resistance to manipulation;
• payer willingness to reimburse a premium;
• prescriber adoption;
• institutional procurement criteria;
• available opioid stewardship budgets;
• absence of an equally effective oxycodone alternative.

The commercial case is stronger if the product reduces diversion or supports controlled dispensing in emergency, dental, orthopedic, or post-surgical settings.

3. Institutional unit-dose product

Hospitals and ambulatory surgery centers may value:

• unit-dose blister packaging;
• barcode-readable identification;
• tamper-evident packaging;
• small package sizes;
• automated dispensing cabinet compatibility;
• reduced waste and reconciliation burden.

This opportunity is operational rather than patent-led. Packaging, serialization, and supply reliability may matter more than the tablet itself.

4. Gastrointestinal-risk differentiated product

Aspirin creates a potential formulation opportunity around gastric tolerability. A gastroprotective presentation could be positioned for selected patients who need both opioid and anti-inflammatory analgesia. The regulatory burden would be substantial because the sponsor would need to establish:

• aspirin and oxycodone bioequivalence or justified pharmacokinetic comparability;
• preservation of analgesic effect;
• reduced gastric injury or clinically relevant tolerability benefit;
• compatibility with rapid pain relief;
• absence of unacceptable interaction between the protective system and opioid exposure.

This is a higher-risk opportunity than a standard generic but could support 505(b)(2) positioning if the product provides a demonstrable clinical advantage.

5. Combination-product lifecycle management

A sponsor could use the combination as part of a broader multimodal pain portfolio, pairing it commercially with:

• naloxone access programs;
• non-opioid analgesics;
• prescribing decision support;
• postoperative protocols;
• controlled dispensing systems.

The product would need a clear role within opioid-sparing treatment pathways. Marketing that encourages broader opioid use would create significant regulatory and reputational risk.

Which companies compete in the oxycodone and aspirin market?

The market has historically included the brand owner or distributor of Percodan and generic opioid manufacturers. Competition is influenced by DEA quotas, FDA approvals, contract manufacturing capacity, opioid litigation exposure, and wholesaler access.

Relevant competitive groups include:

• branded and specialty opioid manufacturers;
• established generic companies with Schedule II manufacturing infrastructure;
• contract development and manufacturing organizations;
• abuse-deterrent opioid developers;
• hospital-focused suppliers;
• pharmaceutical packaging and unit-dose specialists.

The strongest competitors are not necessarily companies with the largest patent portfolios. They are companies with validated controlled-substance operations, stable active pharmaceutical ingredient supply, quota access, state licensing, and established opioid distribution channels.

What generic entry risks exist for oxycodone and aspirin?

Generic entry risk is high for a conventional immediate-release tablet because:

• original exclusivity has expired;
• active ingredients are well established;
• standard excipients are widely available;
• manufacturing processes are conventional;
• clinical differentiation is limited;
• therapeutic substitution from other opioid combinations is strong.

The principal barriers are regulatory and operational rather than patent-based. A generic applicant must manage:

• Schedule II registration;
• DEA procurement and production quotas;
• opioid settlement and compliance obligations;
• FDA inspection readiness;
• supply-chain security;
• controlled-substance recordkeeping;
• product diversion monitoring;
• state-level distribution rules.

An incumbent’s strongest defenses may include manufacturing scale, customer contracts, reliable supply, and a differentiated abuse-deterrent formulation rather than patent litigation.

What patent litigation and Paragraph IV activity affect the product?

Paragraph IV risk is likely to be limited for an ordinary legacy oxycodone-and-aspirin tablet because the core product protection is old. Paragraph IV activity becomes more relevant if a sponsor introduces:

• an abuse-deterrent formulation;
• a modified-release product;
• a gastroprotective dosage form;
• a patented manufacturing process;
• a new strength or dosage form;
• a 505(b)(2) product with listed patents.

A patent holder could face challenges based on anticipation, obviousness, written description, enablement, non-infringement, or improper Orange Book listing. For a conventional formulation, composition claims would be vulnerable if they broadly cover known excipients and routine manufacturing techniques.

How does oxycodone and aspirin compare with oxycodone and acetaminophen?

Factor	Oxycodone and aspirin	Oxycodone and acetaminophen
Anti-inflammatory effect	Present	Limited
Bleeding risk	Higher due to aspirin	Lower than aspirin combination, but not absent
Hepatic toxicity concern	Lower than acetaminophen-specific risk	Dose-related acetaminophen hepatotoxicity
GI toxicity	Significant	Generally lower
Market acceptance	Narrower	Historically broader
Perioperative suitability	Often limited by bleeding concerns	More commonly used, subject to liver-risk limits
Differentiation potential	Gastroprotection and abuse deterrence	Abuse deterrence, lower-acetaminophen formulations, modified release
Commercial outlook	Niche and mature	Larger historical market, though opioid use is declining

The aspirin combination may have a role where anti-inflammatory activity is valued and bleeding risk is manageable. It is less attractive where clinicians prefer control over acetaminophen or aspirin exposure independently.

How strong is the patent estate for oxycodone and aspirin?

The patent estate for a basic oxycodone-and-aspirin immediate-release tablet is weak. A defensible new estate would need claims tied to measurable technical performance.

Patent strategy	Estimated strategic strength
Basic composition with conventional excipients	Low
Routine tablet coating	Low
Improved aspirin stability with comparative data	Moderate
Abuse-deterrent matrix with route-specific evidence	Moderate to strong
Gastroprotective delivery with clinical evidence	Moderate
Novel multilayer release architecture	Moderate
Manufacturing process with reproducible quality advantage	Moderate
Unit-dose packaging alone	Usually limited patent value, stronger trade-secret value

The most durable protection would combine patents with regulatory differentiation, proprietary manufacturing, and commercial contracts.

What are the likely generic launch scenarios?

Standard generic launch

A low-cost immediate-release tablet enters after regulatory approval and competes primarily through wholesalers, hospitals, and pharmacies. The product faces price pressure and limited volume growth.

Limited-supply institutional launch

The sponsor targets hospitals and surgery centers with unit-dose packaging, controlled dispensing, and dependable supply. Margins may be better than in retail generic channels, but total volume is smaller.

Abuse-deterrent launch

The sponsor seeks premium positioning through formulation technology and regulatory labeling. Commercial success depends on reimbursement, prescriber confidence, and evidence that the formulation changes real-world utilization or diversion.

505(b)(2) differentiated launch

The product adds gastroprotection, altered release, or another clinically meaningful feature. Development costs and regulatory requirements increase, but the sponsor may obtain a more defensible market position.

What geographic coverage matters for commercialization?

The United States is the most relevant market because of Percodan history, opioid regulation, and the Orange Book pathway. International expansion is constrained by:

• different opioid scheduling rules;
• country-specific controlled-drug quotas;
• local generic-registration requirements;
• divergent aspirin labeling;
• narcotics import and export permits;
• local pharmacovigilance obligations;
• differing acceptance of fixed-dose opioid combinations.

A global strategy would require country-by-country assessment of opioid controls, not merely patent family coverage. Patent rights may be expired in all major jurisdictions while regulatory and supply-chain barriers remain materially different.

Key Takeaways

• Oxycodone and aspirin is a mature, low-exclusivity combination historically associated with Percodan.
• The basic immediate-release tablet has limited patent strength and high generic-entry exposure.
• The best excipient strategy prioritizes aspirin moisture stability, oxycodone content uniformity, rapid release, and tablet robustness.
• Direct compression or dry granulation may be preferable to aqueous processing where aspirin stability is critical.
• Abuse-deterrent technology is the clearest formulation-led differentiation opportunity.
• Gastroprotective delivery could support a 505(b)(2) strategy but would require meaningful clinical and pharmacokinetic evidence.
• Commercial opportunities are stronger in institutional supply, unit-dose packaging, controlled distribution, and differentiated formulations than in a standard retail generic.
• Schedule II controls, DEA quotas, manufacturing compliance, and distribution security are more important barriers than legacy patent protection.
• The product has a narrower market than oxycodone/acetaminophen because aspirin increases gastrointestinal and bleeding concerns.
• Any new product must be evaluated against FDA Orange Book status, current reference-product availability, opioid labeling requirements, and applicable abuse-deterrent guidance.

FAQs

Is oxycodone and aspirin still commercially relevant?

It is commercially relevant as a legacy combination and potential niche product, but its market is narrower than oxycodone/acetaminophen because of aspirin-related bleeding and gastrointestinal risks.

Can an oxycodone-and-aspirin product qualify as abuse-deterrent?

Yes, but only if the formulation demonstrates meaningful resistance to relevant manipulation routes under FDA’s abuse-deterrent evaluation framework. Tablet hardness alone is unlikely to support broad abuse-deterrent labeling.

Which excipients are most important for aspirin stability?

Low-moisture diluents, controlled-granulation systems, protective coatings, and moisture-barrier packaging are central. The formulation must limit water exposure throughout manufacture and shelf life.

Would a gastroprotective oxycodone-and-aspirin product require new clinical studies?

Potentially. The regulatory pathway would depend on the nature of the formulation change and the claims sought. A sponsor would need to establish appropriate pharmacokinetic comparability and support any claim of reduced gastrointestinal injury or improved tolerability.

Is a patent license likely to be required for a standard generic tablet?

For a conventional legacy immediate-release product, a license is generally less likely to be the principal entry requirement than FDA approval, controlled-substance authorization, manufacturing capacity, and supply-chain compliance. New formulation patents could change that assessment.

References

1. U.S. Food and Drug Administration. (n.d.). Percodan prescribing information. FDA.
2. U.S. Food and Drug Administration. (n.d.). Oxycodone hydrochloride and aspirin labeling information. FDA.
3. U.S. Drug Enforcement Administration. (n.d.). Drug scheduling and controlled-substance requirements. U.S. Department of Justice.
4. U.S. Food and Drug Administration. (2022). Opioid analgesic risk evaluation and mitigation strategy. FDA.
5. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
6. U.S. Food and Drug Administration. (2015). Guidance for industry: Abuse-deterrent opioids: Evaluation and labeling. FDA.