List of Excipients in Branded Drug HYDROCODONE BITARTRATE AND ASPIRIN

Generic Drugs Containing HYDROCODONE BITARTRATE AND ASPIRIN

Company	Ingredient	NDC	Excipient
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	ANHYDROUS LACTOSE
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	CELLULOSE, MICROCRYSTALLINE
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	CROSPOVIDONE
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	HYDROXYPROPYL CELLULOSE
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	SILICON DIOXIDE
LGM PHARMA SOLUTIONS LLC	hydrocodone bitartrate and aspirin	79739-7182	STARCH, CORN

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

# Of NDCs	Excipient
1	ANHYDROUS LACTOSE
1	CELLULOSE, MICROCRYSTALLINE
1	CROSPOVIDONE
1	HYDROXYPROPYL CELLULOSE
1	SILICON DIOXIDE
1	STARCH, CORN

Hydrocodone Bitartrate and Aspirin Excipient Strategy, Patent Protection, and Commercial Opportunities

Last updated: August 18, 2026

Hydrocodone bitartrate and aspirin is an established immediate-release opioid analgesic combination with limited modern patent protection and substantial regulatory constraints. The main commercial opportunity is a low-cost generic or niche branded product supported by manufacturing reliability, tablet differentiation, supply continuity, and compliant risk controls rather than by broad composition-of-matter exclusivity.

A commercially viable formulation must control aspirin-related gastrointestinal degradation, hydrocodone content uniformity, tablet friability, moisture exposure, and opioid diversion risk. The combination also faces competitive disadvantages against hydrocodone-acetaminophen products, NSAID combinations such as hydrocodone-ibuprofen, and nonopioid pain treatments.

What is hydrocodone bitartrate and aspirin?

Hydrocodone bitartrate and aspirin is an oral fixed-dose combination containing a semisynthetic opioid agonist and aspirin, an analgesic, antipyretic, and antiplatelet agent. Historical products were supplied as immediate-release tablets, commonly containing hydrocodone bitartrate at 5 mg, 7.5 mg, or 10 mg per tablet with aspirin at approximately 300 mg or 500 mg, depending on the product.

Hydrocodone is converted to morphine-like analgesic activity through opioid receptor agonism. Aspirin provides nonopioid analgesia and inhibits platelet aggregation through irreversible cyclooxygenase inhibition.

The product category is materially different from hydrocodone-acetaminophen products. Aspirin has gastrointestinal bleeding, ulceration, platelet inhibition, renal, and hypersensitivity risks that are not interchangeable with acetaminophen toxicity risks.

Attribute	Hydrocodone bitartrate and aspirin
Dosage form	Immediate-release oral tablet
Drug category	Opioid analgesic plus salicylate analgesic
Controlled-substance status	Hydrocodone-containing products are Schedule II in the United States
Primary risks	Respiratory depression, misuse, dependence, overdose, gastrointestinal bleeding, renal injury
Typical development route	ANDA for a therapeutically equivalent product, or 505(b)(2) for a materially differentiated product
Main formulation challenge	Maintaining aspirin stability while achieving hydrocodone uniformity and acceptable tablet performance
Main commercial barrier	Limited differentiation and stringent opioid controls
Biosimilar relevance	None; this is a small-molecule drug, not a biologic

FDA labeling for hydrocodone-containing products requires opioid class warnings, including risks of addiction, abuse, misuse, respiratory depression, and neonatal opioid withdrawal syndrome.[1]

What excipients are suitable for hydrocodone bitartrate and aspirin tablets?

A conventional immediate-release formulation can use a relatively simple excipient system. The preferred approach is direct compression when the active pharmaceutical ingredients and excipients have adequate flow, compressibility, and content-uniformity performance. Wet granulation is possible but increases exposure to water and may complicate aspirin stability.

Core excipient functions

Formulation function	Candidate excipient classes	Commercial rationale
Diluent	Microcrystalline cellulose, anhydrous lactose, dibasic calcium phosphate	Controls tablet weight and improves compressibility
Binder	Povidone, copovidone, low-substituted hydroxypropyl cellulose	Supports granule or tablet strength
Disintegrant	Crospovidone, sodium starch glycolate, croscarmellose sodium	Supports rapid immediate-release dissolution
Glidant	Colloidal silicon dioxide	Improves powder flow and content uniformity
Lubricant	Sodium stearyl fumarate, low-level magnesium stearate	Reduces ejection force while limiting dissolution impact
Antiadherent	Talc or compatible silica system	Controls sticking during compression
Film coating	Hypromellose, polyvinyl alcohol, polyethylene glycol, titanium dioxide where permitted	Improves appearance, handling, and light protection
Moisture control	Desiccant packaging, high-barrier blister or bottle	Reduces aspirin hydrolysis and odor formation

A formulation should minimize alkaline excipients and uncontrolled moisture. Aspirin hydrolyzes to salicylic acid and acetic acid under unfavorable conditions. The resulting degradation can affect assay, dissolution, odor, and stability. Calcium carbonate and other alkaline materials may be unsuitable unless compatibility data support their use.

Magnesium stearate requires particular control. Excessive concentration or prolonged blending can reduce tablet wettability and slow dissolution. Sodium stearyl fumarate can be evaluated where the development team needs lower hydrophobicity, although it can alter compaction behavior and tablet robustness.

Is wet granulation appropriate?

Wet granulation is generally less attractive for aspirin-containing tablets unless the process uses tightly controlled water exposure or a nonaqueous system. A dry granulation or direct-compression platform reduces hydrolysis risk and can shorten development time.

The principal process controls are:

• Low and controlled environmental humidity.
• Short lubricant blending time.
• Narrow particle-size distributions for both active ingredients.
• Adequate segregation testing during hopper discharge and compression.
• Stability testing for aspirin hydrolysis and hydrocodone degradation.
• Packaging validation under high-temperature and high-humidity conditions.

A multilayer or coated-particle approach may improve compatibility, but it increases cost and can create new dissolution and manufacturing risks. Such technology is commercially justified only if it delivers a measurable stability, abuse-deterrence, or dose-flexibility advantage.

What excipient strategy best supports commercial development?

The most practical strategy is a low-moisture, immediate-release tablet using direct compression or dry granulation, with excipients selected from widely accepted compendial and regulatory databases.

A baseline platform could include microcrystalline cellulose or anhydrous lactose as the primary diluent, crospovidone as the disintegrant, colloidal silicon dioxide as the glidant, and a controlled amount of magnesium stearate or sodium stearyl fumarate as the lubricant. A protective film coat and high-barrier packaging can provide further handling and stability benefits.

The formulation should avoid unnecessary complexity. Each additional excipient increases extractables, compatibility, regulatory, and supply-chain review. A simple formula also improves generic manufacturing economics.

How can excipients improve product differentiation?

Excipients can support differentiation in four areas:

1. Stability. A low-moisture system and high-barrier packaging can extend shelf life or reduce aspirin degradation.
2. Patient handling. Film coating, tablet shape, embossing, and reduced friability can improve usability.
3. Manufacturing performance. Better flow and compression can reduce weight variation and tablet rejects.
4. Formulation defensibility. A specific excipient ratio, coating system, or manufacturing process may support patent claims if it produces unexpected performance.

Excipients should not be positioned as an abuse-deterrence solution without evidence. FDA's abuse-deterrent framework evaluates the finished dosage form and its resistance to specific manipulation or abuse routes, not the presence of a particular excipient alone.[2]

What patents protect hydrocodone bitartrate and aspirin?

The active ingredients are old molecules, and broad composition-of-matter patent protection for hydrocodone bitartrate and aspirin is not a current commercial barrier. Historical combination products may have been covered by product, formulation, process, or method-of-use patents, but those rights are generally distinct from current generic approval requirements.

The potentially relevant patent categories are:

Patent category	Likely relevance
Combination composition	Low for an old hydrocodone-aspirin combination
Tablet formulation	Possible where a specific excipient system or release profile is claimed
Stability formulation	Possible where degradation control produces unexpected results
Abuse-deterrent technology	Potentially significant for a new product, but requires technical and regulatory support
Manufacturing process	Possible for granulation, coating, segregation control, or particle engineering
Method of use	Limited because opioid analgesic indications are mature and broadly known
Packaging	Possible but usually narrow and commercially weaker than formulation claims

No single patent number should be treated as controlling for the entire product category. Patent review must be conducted against the specific reference listed drug, NDA, dosage strength, formulation, and intended ANDA or 505(b)(2) pathway.

What is the Orange Book status of hydrocodone bitartrate and aspirin?

The Orange Book status depends on the specific FDA-approved product and whether the product remains listed as an active reference drug. FDA's Approved Drug Products with Therapeutic Equivalence Evaluations identifies active and discontinued products, patent listings, exclusivity, and therapeutic-equivalence information.[3]

Hydrocodone bitartrate and aspirin products have largely been legacy or discontinued products rather than dominant current branded products. A company seeking approval cannot assume that a historical brand name automatically remains an active reference listed drug. The regulatory strategy must distinguish among:

• An active reference listed drug.
• A discontinued product that FDA determines was not withdrawn for safety or efficacy reasons.
• A product requiring a 505(b)(2) application because no suitable reference product exists.
• A formulation requiring a new clinical or bridging package.

If an ANDA relies on an active reference listed drug, patent certifications under section 505(j) may include Paragraph I, II, III, or IV certifications. A Paragraph IV certification alleges that a listed patent is invalid, unenforceable, or not infringed and can trigger patent litigation and a potential 30-month stay under the Hatch-Waxman framework.[4]

When does hydrocodone bitartrate and aspirin lose exclusivity?

Broad market exclusivity for the underlying combination has effectively expired because the active ingredients and the immediate-release combination have long commercial histories. The relevant current question is whether a particular FDA reference product has unexpired listed patents or regulatory exclusivity.

Exclusivity type	Relevance to this product
New chemical entity exclusivity	Not available for this old combination
Five-year NCE exclusivity	Not applicable
Three-year clinical-investigation exclusivity	Possible only for a qualifying new application and new clinical investigations
Orphan exclusivity	Not relevant to routine analgesic use
Pediatric exclusivity	Product-specific and not inherent to the combination
Formulation patent term	Depends on the specific patent and expiration date
Method-of-use patent term	Depends on the patented indication and listed use

A generic manufacturer should focus on current FDA listings and live patents, not historical product literature. Older patents covering basic tablets, conventional binders, or ordinary immediate-release delivery are unlikely to create meaningful exclusivity today unless a narrow improvement patent remains enforceable.

Are Paragraph IV challenges likely?

Paragraph IV activity is more likely when a current branded product has an active formulation or abuse-deterrent patent. It is less likely for a conventional legacy hydrocodone-aspirin tablet with no significant branded market.

A potential applicant would evaluate:

• Whether FDA identifies an active reference listed drug.
• Whether Orange Book patents cover the exact strength and dosage form.
• Whether the proposed formulation falls within each patent claim.
• Whether the product requires a 30-month stay analysis.
• Whether state opioid restrictions create launch delays independent of patent litigation.

For a standard immediate-release generic, the principal approval risk may be regulatory and commercial rather than patent litigation. A newly patented abuse-deterrent formulation would create a different risk profile, with greater patent exposure and higher development cost.

What regulatory status applies to hydrocodone-containing products?

Hydrocodone combination products are controlled substances under the Controlled Substances Act. FDA-approved opioid products are subject to labeling, postmarketing, risk-management, supply-chain, and prescribing controls. DEA registration and controlled-substance security requirements apply to manufacturing, distribution, and inventory management.[5]

A product must address:

• Opioid analgesic labeling requirements.
• Drug-drug interaction warnings.
• Respiratory-depression risk.
• Abuse, misuse, and diversion.
• Acetaminophen-free positioning, without implying that aspirin is risk-free.
• Aspirin-related gastrointestinal bleeding and platelet-inhibition risks.
• Contraindications involving salicylate hypersensitivity and certain bleeding conditions.
• Packaging, serialization, and controlled-substance distribution requirements.

A commercial product should not promote aspirin as a safer substitute for acetaminophen. Its risk profile is different, not uniformly lower.

What commercial opportunities exist for hydrocodone bitartrate and aspirin?

The strongest opportunities are operational and niche rather than premium mass-market opportunities.

Generic supply continuity

A manufacturer could target hospitals, long-term-care providers, specialty wholesalers, and public-sector purchasers that value reliable supply. Hydrocodone shortages and manufacturer exits can create temporary openings, although controlled-substance quotas and distribution restrictions limit rapid volume expansion.

Aspirin-based analgesic positioning

Some prescribers may prefer an aspirin-containing opioid combination for patients in whom acetaminophen exposure is undesirable. This is a narrow opportunity because aspirin is unsuitable for patients with active ulcer disease, bleeding risk, aspirin-sensitive asthma, anticoagulant use, or certain renal conditions.

Private-label and contract manufacturing

A validated immediate-release platform can support private-label supply if the manufacturer holds or licenses the applicable ANDA. Contract manufacturing can lower fixed commercial costs, but controlled-substance handling requires specialized facilities and compliance systems.

Dose and package differentiation

Commercial differentiation may come from:

• Multiple hydrocodone strengths.
• Unit-dose blister packaging.
• Tamper-evident packaging.
• Hospital-oriented pack sizes.
• High-barrier bottles with desiccant.
• Tablet identification and serialization.
• Consistent supply across strengths.

These measures usually support contracting and procurement rather than premium pricing.

How strong is the patent estate for hydrocodone bitartrate and aspirin?

The patent estate for a conventional hydrocodone bitartrate and aspirin tablet is likely weak to moderate from a blocking perspective. Broad ingredient and basic combination claims are old. New protection would need to rely on a specific technical improvement.

Asset	Blocking strength	Commercial value
Basic hydrocodone-aspirin composition	Low	Low
Conventional immediate-release tablet	Low	Low
Moisture-stable formulation	Moderate if technically demonstrated	Moderate
Abuse-deterrent platform	Moderate to high if validated	Potentially high
Novel release profile	Moderate	Depends on clinical need
Manufacturing process	Low to moderate	Useful against direct copying
Packaging-only claim	Low	Limited
New indication	Low to moderate	Requires clinical and regulatory support

Patent value depends on claim breadth, enablement, freedom-to-operate scope, and whether competitors can design around the excipient ratios or process steps.

Which companies are challenging or competing with this product?

Competition is primarily from generic opioid and nonopioid products rather than from active branded hydrocodone-aspirin franchises.

Relevant competitors include:

• Hydrocodone-acetaminophen tablets.
• Hydrocodone-ibuprofen tablets.
• Oxycodone-acetaminophen products.
• Codeine-aspirin combinations.
• Tramadol-based products.
• NSAIDs and nonopioid analgesics.
• Extended-release and abuse-deterrent opioid products.

Generic manufacturers with controlled-substance infrastructure can compete on price and supply reliability. Large opioid manufacturers may have stronger distribution and compliance capabilities, while smaller manufacturers can compete in underserved strengths or institutional channels.

What generic launch scenarios exist?

Scenario 1: Conventional ANDA launch

This is the lowest-cost scenario if an active reference listed drug and suitable therapeutic-equivalence pathway exist. The product competes on price, supply, and contracting.

Scenario 2: 505(b)(2) reformulation

A 505(b)(2) product could use a different excipient system, package, strength, or delivery feature. It may obtain differentiated labeling or claims but requires a stronger development package and faces higher regulatory cost.

Scenario 3: Stability-led product

A manufacturer could develop a moisture-controlled product with documented shelf-life or packaging advantages. This supports procurement differentiation but may not justify a large price premium.

Scenario 4: Abuse-deterrent product

An abuse-deterrent formulation could target institutional or payer demand, but development, clinical, human-factors, manipulation, and patent costs would be substantially higher. The market opportunity would depend on FDA labeling and demonstrable abuse-deterrence performance.

What manufacturing and intellectual-property barriers exist?

The principal manufacturing barriers are controlled-substance compliance, active-ingredient segregation, content uniformity, aspirin stability, and supply-chain controls.

Critical development studies include:

• API-excipient compatibility.
• Blend uniformity and segregation testing.
• Dissolution across pH conditions.
• Accelerated and long-term stability.
• Aspirin hydrolysis monitoring.
• Hydrocodone assay and impurity profiling.
• Tablet hardness, friability, and disintegration.
• Packaging moisture ingress.
• Scale-up validation.
• Cleaning validation for hydrocodone residues.

The main IP barrier is not the old combination itself. It is the possibility that a specific current product uses a protected formulation, abuse-deterrent platform, or manufacturing process. Freedom-to-operate analysis should therefore focus on excipient ratios, coating technology, particle engineering, release behavior, and product-specific Orange Book listings.

Key Takeaways

• Hydrocodone bitartrate and aspirin is a mature small-molecule combination with limited broad patent protection.
• The most practical dosage form is a low-moisture immediate-release tablet made by direct compression or dry granulation.
• Aspirin stability is the central excipient and packaging issue.
• Avoiding excess moisture and alkaline excipients is important for controlling aspirin hydrolysis.
• The commercial opportunity is strongest in generic supply continuity, institutional procurement, private label, and niche aspirin-based prescribing.
• A new product could obtain stronger protection through a validated abuse-deterrent, stability-enhancing, or release-modifying formulation.
• FDA and DEA controls materially affect manufacturing, distribution, forecasting, and launch timing.
• Paragraph IV litigation is less likely for a conventional legacy product than for a current branded reformulation.
• Biosimilar competition is irrelevant because the product is a small-molecule combination.
• Commercial success depends more on regulatory pathway, controlled-substance infrastructure, stability, and supply reliability than on the underlying drug combination.

FAQs

Can hydrocodone bitartrate and aspirin be reformulated as an abuse-deterrent tablet?

Yes. A reformulated product could use physical, chemical, or delivery-system technologies intended to resist crushing, extraction, dissolution, or injection. FDA labeling claims would require evidence under the agency's abuse-deterrent opioid guidance.[2]

Does aspirin create a patent advantage over hydrocodone-acetaminophen?

Usually not. Aspirin changes the clinical and safety profile, but the active ingredients are old. Any meaningful patent advantage would likely come from a specific formulation, stability system, or delivery technology.

Is a hydrocodone-aspirin product eligible for an ANDA?

Potentially, if FDA recognizes a suitable reference listed drug and the proposed product meets sameness and therapeutic-equivalence requirements. If the reference product or formulation pathway is unsuitable, a 505(b)(2) application may be necessary.

What packaging is most suitable for aspirin-containing opioid tablets?

High-barrier packaging with controlled moisture ingress is generally preferable. Unit-dose blisters may support institutional handling, while bottles with desiccants may provide lower-cost retail distribution.

Could an aspirin-containing hydrocodone product replace hydrocodone-acetaminophen?

No broad substitution assumption is justified. The products have different contraindications, interaction risks, toxicity profiles, and prescribing considerations. Product selection must reflect the patient's bleeding, gastrointestinal, renal, hepatic, and opioid-risk profile.

References

1. U.S. Food and Drug Administration. (2023). Opioid analgesic risk evaluation and mitigation strategy. https://www.fda.gov
2. U.S. Food and Drug Administration. (2015). Guidance for industry: Abuse-deterrent opioids: Evaluation and labeling. https://www.fda.gov
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov
4. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. https://www.fda.gov
5. Drug Enforcement Administration. (2024). Controlled substances schedules and regulatory requirements. https://www.dea.gov
6. United States Pharmacopeia. (2024). United States Pharmacopeia and National Formulary. U.S. Pharmacopeial Convention.