List of Excipients in Branded Drug HYDROCODONE BITARTATE AND ACETAMINOPHEN

Generic Drugs Containing HYDROCODONE BITARTATE AND ACETAMINOPHEN

Company	Ingredient	NDC	Excipient
Aidarex Pharmaceuticals LLC	hydrocodone bitartrate, acetaminophen	33261-881	CELLULOSE, MICROCRYSTALLINE
Aidarex Pharmaceuticals LLC	hydrocodone bitartrate, acetaminophen	33261-881	CROSPOVIDONE
Aidarex Pharmaceuticals LLC	hydrocodone bitartrate, acetaminophen	33261-881	MAGNESIUM STEARATE
Aidarex Pharmaceuticals LLC	hydrocodone bitartrate, acetaminophen	33261-881	POVIDONE

What are the Most Frequently-Used Excipients in HYDROCODONE BITARTATE AND ACETAMINOPHEN?

# Of NDCs	Excipient
4	CELLULOSE, MICROCRYSTALLINE
1	CROSCARMELLOSE SODIUM
4	CROSPOVIDONE
4	MAGNESIUM STEARATE

Hydrocodone Bitartrate and Acetaminophen Excipient Strategy, Patent Risks, and Commercial Opportunities

Last updated: September 28, 2026

Hydrocodone bitartrate and acetaminophen is a mature, genericized opioid combination with limited composition-of-matter protection and substantial regulatory controls. Commercial opportunity is concentrated in excipient-enabled differentiation: abuse-deterrent tablets, lower-acetaminophen strengths, orally disintegrating or liquid dosage forms, improved swallowability, taste masking, stability, and manufacturing-cost reduction. The strongest opportunities require a clear FDA pathway, controlled-substance compliance, and evidence that the excipient system improves a measurable product attribute.

What is the market and regulatory status of hydrocodone bitartrate and acetaminophen?

Hydrocodone bitartrate and acetaminophen products are immediate-release oral combination medicines regulated as prescription controlled substances. Hydrocodone is a Schedule II controlled substance in the United States. The products are approved for pain and are marketed in multiple tablet, capsule, and oral-solution presentations.

Common tablet strengths include:

Hydrocodone bitartrate	Acetaminophen
2.5 mg	300 mg
5 mg	300 mg or 325 mg
7.5 mg	300 mg or 325 mg
10 mg	300 mg or 325 mg

Product availability varies by manufacturer and national drug shortage conditions. The 5 mg/325 mg, 7.5 mg/325 mg, and 10 mg/325 mg strengths are widely recognized commercial presentations. FDA labeling identifies the principal risks as respiratory depression, misuse, abuse, addiction, overdose, and acetaminophen-associated liver injury.[1]

The product category has no meaningful biosimilar pathway. A follow-on product would generally proceed through an abbreviated new drug application, an authorized generic structure, or, for a materially different dosage form or delivery profile, a 505(b)(2) application.[2]

What excipients are used in hydrocodone-acetaminophen tablets?

Commercial immediate-release tablets commonly use a conventional excipient platform consisting of a filler, binder, disintegrant, lubricant, glidant, coating system, and colorant. Exact compositions differ by manufacturer and strength.

Typical excipient functions

Excipient class	Typical function	Commercial relevance
Microcrystalline cellulose	Filler and dry binder	Supports direct compression and tablet hardness
Lactose or other soluble filler	Mass adjustment and mouthfeel	Affects compressibility and moisture behavior
Povidone	Binder	Improves granule strength and content uniformity
Sodium starch glycolate or crospovidone	Superdisintegrant	Controls tablet breakup and dissolution
Croscarmellose sodium	Disintegrant	Supports rapid release at low use levels
Colloidal silicon dioxide	Glidant and moisture control	Improves powder flow and manufacturing consistency
Magnesium stearate	Lubricant	Reduces punch friction but can slow dissolution if overused
Opadry-type coating systems	Film coating, color, branding	Protects tablets and improves identification
Crospovidone or polymers	Adsorption and matrix control	Can support abuse-deterrent or taste-masking designs

The principal technical challenge is balancing rapid immediate release with robust mechanical strength. Hydrocodone is present at a low mass relative to the excipient load, so content uniformity and segregation control are important. Acetaminophen contributes most of the tablet mass and can affect compression, dissolution, and tablet size.

What excipient strategy best supports commercial differentiation?

The best strategy depends on whether the target is a standard ANDA, an authorized generic, or a differentiated 505(b)(2) product.

Strategy 1: Low-cost conventional immediate-release tablet

A conventional tablet has the lowest development and regulatory risk. The formulation objective is to match the reference product's release profile while minimizing manufacturing complexity.

A practical platform would use:

• Direct compression where powder flow and content uniformity permit.
• Microcrystalline cellulose or a comparable filler-binder.
• Crospovidone or croscarmellose sodium for rapid disintegration.
• Low-level colloidal silicon dioxide for flow.
• Magnesium stearate with controlled blending time.
• A thin film coat for identification and handling.

The commercial advantage is limited. Generic competition keeps prices low, and an excipient change alone generally does not create durable differentiation. The opportunity is strongest when the formulation reduces tablet weight, improves yield, eliminates wet granulation, or addresses a supply-constrained excipient.

Strategy 2: Lower-acetaminophen formulation

A lower-acetaminophen ratio can address cumulative acetaminophen exposure while maintaining a familiar hydrocodone strength. This strategy has regulatory and commercial value because the acetaminophen component is associated with dose-related hepatotoxicity risk.[1]

The formulation must preserve:

• Hydrocodone content uniformity;
• immediate-release dissolution;
• tablet size suitable for chronic dispensing;
• physical stability;
• dose-identification controls; and
• labeling consistency with the approved product.

A lower-acetaminophen product may require a new strength, a new reference product comparison, or a 505(b)(2) approach depending on the product design and regulatory basis. The benefit is larger if the sponsor can establish a clinically relevant dosing or safety rationale rather than merely changing the tablet composition.

Strategy 3: Abuse-deterrent formulation

Abuse-deterrent excipient systems can use high-hardness matrices, gelling polymers, aversive agents, or crush-resistant architectures. FDA evaluates abuse-deterrent products against route-specific manipulation and abuse studies described in its guidance.[3]

For hydrocodone-acetaminophen, a sponsor must manage a difficult design constraint: the product should resist crushing, grinding, extraction, or rapid dissolution while remaining an immediate-release oral medicine when taken as directed.

Potential excipient tools include:

• High-viscosity hydrophilic polymers;
• polyethylene oxide-based matrices;
• silicified microcrystalline cellulose;
• wax or lipid components;
• ion-exchange resins;
• polymeric barriers;
• aversive flavor systems; and
• tamper-evident coatings.

Abuse-deterrence claims are expensive to support and may not produce full market exclusivity. FDA labeling depends on the evidence package, and an abuse-deterrent designation does not prevent abuse or guarantee reduced addiction risk.[3] The commercial case is strongest for institutional purchasers, managed-care formularies, and branded or specialty channels that value product differentiation.

Strategy 4: Orally disintegrating and taste-masked dosage forms

An orally disintegrating tablet could target patients with swallowing difficulty, although opioid products require careful control of inadvertent exposure and dose administration. A taste-masked product would need to prevent unacceptable bitterness from hydrocodone and acetaminophen.

Relevant excipient systems include:

• Mannitol for cooling mouthfeel and rapid dissolution;
• crospovidone for fast disintegration;
• ion-exchange resins for drug binding;
• polymer coatings for taste masking;
• sucralose or other sweeteners;
• flavors and buffering agents; and
• low-moisture packaging.

This segment has a stronger 505(b)(2) rationale than a conventional tablet because the dosage form and patient-use profile can differ materially from existing products. The development burden includes palatability, dose uniformity, disintegration, moisture stability, and accidental ingestion risk.

Strategy 5: Oral solution and preservative system

Hydrocodone-acetaminophen oral solutions require control of solubility, pH, microbial quality, preservative performance, and dose-measurement accuracy. The formulation must also address the possibility of dosing errors in household use.

Commercially relevant excipients include:

• Co-solvents;
• glycerin or sorbitol;
• buffering agents;
• flavor systems;
• suspending or viscosity-modifying agents;
• chelating agents;
• preservatives; and
• child-resistant packaging components.

An oral solution can serve pediatric or swallowing-impaired populations, but the product has a higher diversion and accidental-overdose risk. A unit-dose cup, oral syringe, or metered dispensing system can create a stronger product proposition than an excipient change alone.

What patents protect hydrocodone bitartrate and acetaminophen products?

The active-ingredient combination is mature. Composition-of-matter protection for hydrocodone and acetaminophen is not the main commercial barrier. Relevant intellectual-property opportunities now tend to involve:

1. Abuse-deterrent formulations.
2. Controlled-release or modified-release systems.
3. Low-acetaminophen dosage ratios.
4. Taste-masked oral dosage forms.
5. Orally disintegrating tablets.
6. Stable oral solutions and preservative systems.
7. Tamper-resistant packaging and dispensing devices.
8. Manufacturing processes that improve content uniformity or reduce solvent use.

Formulation patents

A defensible formulation patent should claim more than a list of conventional excipients. Stronger claim structures can include:

• Defined polymer-to-drug ratios;
• hardness or tensile-strength ranges;
• extraction-resistant dissolution profiles;
• particle-size distributions;
• specified disintegration and dissolution limits;
• stability under accelerated conditions;
• reduced tablet mass;
• controlled moisture activity; or
• a manufacturing sequence tied to a measurable product property.

A claim that merely recites hydrocodone, acetaminophen, a filler, a disintegrant, and a lubricant is vulnerable to anticipation and obviousness challenges.

Method-of-use patents

Method-of-use opportunities are narrower because hydrocodone-acetaminophen is an established analgesic. Potential claims could address:

• Use in a defined patient population;
• reduced acetaminophen exposure;
• opioid-tolerant patients;
• administration through a specific delivery system; or
• a dosing method associated with a distinct safety or pharmacokinetic outcome.

The patent must be supported by credible clinical evidence. A broad pain-treatment claim is unlikely to provide durable differentiation in a crowded field.

What is the Orange Book status of hydrocodone-acetaminophen products?

FDA's Orange Book identifies approved drug products and, where applicable, listed patents and exclusivity. The commercial status of each hydrocodone-acetaminophen product must be assessed by NDA number, manufacturer, dosage form, and strength because listings differ among reference products and approved generic products.[4]

For a conventional generic tablet, the principal regulatory pathway is an ANDA with paragraph I, II, III, or IV patent certifications. Paragraph IV certification is relevant only when the ANDA applicant asserts that a listed patent is invalid, unenforceable, or not infringed.[2]

A formulation sponsor seeking a new product with a novel dosage form may instead pursue 505(b)(2). That pathway can support reliance on FDA findings for the established active ingredients while requiring additional information for the new formulation, delivery system, or clinical use.

When does hydrocodone-acetaminophen lose exclusivity?

The product category has already lost practical market exclusivity for conventional immediate-release tablets. Generic entry is established, and the commercial question is not whether generic competition will occur but whether a differentiated formulation can obtain product-specific protection.

Potential exclusivity categories include:

Protection type	Relevance
New chemical entity exclusivity	Generally not available for this mature combination
ANDA exclusivity	May apply to a first eligible generic challenge to a listed patent
3-year clinical-investigation exclusivity	May apply to certain 505(b)(2) approvals supported by new clinical studies
5-year NCE exclusivity	Generally not applicable
Orphan exclusivity	Not relevant absent an orphan indication
Pediatric exclusivity	Depends on an FDA-requested pediatric study package

Patent term for a newly developed formulation is generally measured from the effective U.S. filing framework and may be subject to patent-term adjustment or restoration. A formulation patent can provide meaningful protection even when the active ingredients are old, but only if the claims cover commercially important product attributes and survive validity challenges.

Which companies are challenging hydrocodone-acetaminophen products?

The market has historically included numerous generic manufacturers and authorized-generic suppliers. Competition is fragmented across companies such as Mallinckrodt, Amneal Pharmaceuticals, Hikma Pharmaceuticals, Teva Pharmaceuticals, Rhodes Pharmaceuticals, Endo-related businesses, and other ANDA holders, depending on the specific strength and product listing.

The relevant competitive groups are:

• Conventional tablet manufacturers;
• oral-solution manufacturers;
• branded or specialty opioid developers;
• contract manufacturers with controlled-substance capability; and
• companies developing abuse-deterrent opioid platforms.

A reliable company-by-company challenge analysis requires matching each manufacturer to a current FDA listing, active product status, and litigation docket. The commercially relevant point is that conventional generic supply is available from multiple sources, while differentiated abuse-deterrent or specialty dosage forms have a narrower field.

What patent litigation and Paragraph IV risks affect the product?

Paragraph IV risk is concentrated in newly patented formulations, not in the established hydrocodone-acetaminophen combination itself. A sponsor launching a new formulation should expect potential litigation involving:

• Obviousness of the excipient combination;
• anticipation by earlier opioid formulations;
• written-description support for broad polymer claims;
• enablement across multiple strengths;
• infringement by generic substitution;
• product-by-process claim scope; and
• freedom to operate around abuse-deterrent technologies.

A Paragraph IV notice can trigger litigation under the Hatch-Waxman Act and may impose a 30-month stay of approval in qualifying circumstances.[2] Settlement agreements can define launch dates, authorized-generic rights, supply arrangements, or licenses to formulation patents. Opioid settlements also face heightened scrutiny because of public-health and controlled-substance considerations.

How strong is the patent estate for an excipient-enabled product?

Patent strength is highest when the formulation produces a technical effect that competitors cannot easily reproduce without entering the claims.

Patent concept	Relative strength
Conventional filler-disintegrant-lubricant blend	Low
Narrow process claim reducing segregation	Moderate if reproducible and non-obvious
Defined abuse-deterrent polymer architecture	Moderate to high
New dosage form with clinical or pharmacokinetic benefit	Moderate to high
Broad “hydrocodone plus excipients” claim	Low
Device-linked dosing system	Moderate
Manufacturing process with measurable critical quality attributes	Moderate

The strongest portfolio normally combines composition claims, process claims, dosage-form claims, and device or packaging claims. Geographic protection should begin in the United States, with filings in Europe, Canada, Australia, Japan, and selected emerging markets only where controlled-substance distribution and commercial demand justify the cost.

What manufacturing and intellectual-property barriers exist?

Hydrocodone manufacturing has barriers beyond ordinary tablet production. A commercial manufacturer needs:

• DEA registration and controlled-substance quotas;
• validated security and inventory controls;
• qualified active-pharmaceutical-ingredient suppliers;
• opioid-specific diversion controls;
• analytical methods for content uniformity and impurities;
• validated cleaning procedures;
• tamper-resistant packaging where appropriate; and
• stable supply of acetaminophen and critical excipients.

For abuse-deterrent products, the manufacturing process can be more important than the ingredient list. Polymer distribution, compression force, granule density, moisture, and coating uniformity can determine whether the product meets its intended manipulation-resistance profile.

What licensing opportunities exist?

Licensing opportunities are most credible in four areas:

1. Abuse-deterrent platform technology.
2. Orally disintegrating or taste-masked delivery systems.
3. Unit-dose or metered liquid-dispensing systems.
4. Contract manufacturing with controlled-substance infrastructure.

A licensee should value the package based on regulatory precedent, freedom to operate, scale-up data, abuse-deterrence evidence, and supply-chain readiness. A patent without reproducible pilot-scale data has limited transaction value.

What generic launch scenarios exist?

Conventional tablet

Generic entry is already established. Launch economics depend on manufacturing cost, procurement contracts, shortage conditions, and the number of active suppliers.

New lower-acetaminophen strength

The sponsor may obtain differentiation through dosing rationale and product-specific regulatory exclusivity, but substitution and payer acceptance remain central risks.

Abuse-deterrent product

Launch may support branded pricing or specialty contracting, but clinical adoption and reimbursement are uncertain. Generic applicants may challenge formulation patents after approval.

Oral solution or orally disintegrating tablet

These products can access narrower patient segments and may achieve less direct price competition. The opportunity is strongest where administration, swallowing, or dosing accuracy is a documented problem.

How does hydrocodone-acetaminophen compare with oxycodone-acetaminophen?

Factor	Hydrocodone-acetaminophen	Oxycodone-acetaminophen
Regulatory class	Schedule II	Schedule II
Common commercial form	Immediate-release tablet and solution	Immediate-release tablet and solution
Generic competition	Extensive	Extensive
Excipient differentiation	Abuse deterrence, lower APAP, liquid and ODT	Similar opportunities
Active-ingredient patent barrier	Mature and limited	Mature and limited
Key safety issue	Opioid risk plus acetaminophen exposure	Opioid risk plus acetaminophen exposure
Commercial moat	Formulation, device, supply, contracting	Formulation, device, supply, contracting

The two categories compete for similar prescriber and payer segments. A hydrocodone-acetaminophen product needs a specific advantage in dose, tolerability, administration, abuse deterrence, or supply reliability to avoid direct generic price competition.

Key Takeaways

• Conventional hydrocodone-acetaminophen tablets are mature generic products with limited active-ingredient exclusivity.
• Excipient strategy is commercially useful only when tied to a measurable product advantage.
• The best opportunities are abuse deterrence, lower-acetaminophen ratios, taste-masked or orally disintegrating dosage forms, and safer liquid-dosing systems.
• Conventional excipient substitution is more likely to reduce cost than create market exclusivity.
• New formulations may use the 505(b)(2) pathway, while ordinary copies generally use ANDAs.
• Patent value depends on technical effect, manufacturing reproducibility, claim breadth, and freedom to operate.
• Controlled-substance registration, quota management, diversion controls, and supply security are material barriers to entry.
• There is no biosimilar risk. The relevant competitive risk is generic substitution and formulation-based Paragraph IV litigation.

Frequently Asked Questions

Can a new excipient alone create exclusivity for hydrocodone-acetaminophen?

Usually not. Exclusivity is more defensible when the excipient produces a novel dosage form, abuse-deterrent property, clinical benefit, or measurable manufacturing advantage supported by patent claims and FDA data.

Is an abuse-deterrent hydrocodone-acetaminophen tablet commercially viable?

It can be viable if the sponsor has convincing manipulation-resistance data, a clear contracting strategy, and a cost structure that supports pricing above conventional generics. FDA does not treat abuse-deterrent labeling as proof that a product cannot be abused.[3]

Does hydrocodone-acetaminophen have biosimilar competition?

No. Biosimilar regulation applies to biologic products. Hydrocodone-acetaminophen is a small-molecule combination product subject to generic and, in some cases, 505(b)(2) pathways.

What is the most defensible formulation patent strategy?

A portfolio covering a defined excipient architecture, critical process parameters, dissolution or extraction behavior, and the resulting dosage form is generally stronger than a broad ingredient list.

Can a liquid formulation support a separate commercial niche?

Yes. Oral solutions can serve patients who cannot swallow tablets and can differentiate through metered dosing, taste masking, stability, preservative performance, and unit-dose packaging. The product must also address dosing-error and controlled-substance risks.

References

1. U.S. Food and Drug Administration. (2024). Hydrocodone bitartrate and acetaminophen prescribing information. FDA.
2. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards. FDA.
3. U.S. Food and Drug Administration. (2015). General principles for evaluating abuse-deterrent opioids: Guidance for industry. FDA.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.