List of Excipients in Branded Drug HYDROCODONE BITARTRATE AND IBUPROFEN

Generic Drugs Containing HYDROCODONE BITARTRATE AND IBUPROFEN

Company	Ingredient	NDC	Excipient
Par Pharmaceutical Inc	hydrocodone bitartrate and ibuprofen	0603-3897	CELLULOSE, MICROCRYSTALLINE
Par Pharmaceutical Inc	hydrocodone bitartrate and ibuprofen	0603-3897	HYPROMELLOSES
Par Pharmaceutical Inc	hydrocodone bitartrate and ibuprofen	0603-3897	MAGNESIUM STEARATE
Par Pharmaceutical Inc	hydrocodone bitartrate and ibuprofen	0603-3897	POLYETHYLENE GLYCOL

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

# Of NDCs	Excipient
2	ANHYDROUS LACTOSE
5	CARNAUBA WAX
12	CELLULOSE, MICROCRYSTALLINE
1	COLLOIDAL SILICON DIOXIDE

Hydrocodone Bitartrate and Ibuprofen Excipient Strategy and Commercial Opportunities

Last updated: August 3, 2026

Hydrocodone bitartrate and ibuprofen is a mature immediate-release combination product with limited active-ingredient exclusivity and substantial regulatory controls. The commercial opportunity is concentrated in reliable low-dose tablet manufacturing, excipient-enabled product differentiation, supply-chain control, and contract development rather than in new chemical-entity patent protection.

The reference product, Vicoprofen, contains hydrocodone bitartrate equivalent to 7.5 mg hydrocodone and 200 mg ibuprofen per tablet. FDA approved the product for short-term management of acute pain, generally for no more than 10 days, in patients requiring an opioid analgesic when alternative treatments are inadequate (FDA, 2024a). The product is a Schedule II controlled substance.

What is the FDA status of hydrocodone bitartrate and ibuprofen?

Hydrocodone bitartrate and ibuprofen is an FDA-approved immediate-release opioid/nonsteroidal anti-inflammatory drug combination.

Attribute	Product status
Reference brand	Vicoprofen
Active ingredients	Hydrocodone bitartrate and ibuprofen
Reference strength	7.5 mg hydrocodone equivalent and 200 mg ibuprofen per tablet
Dosage form	Immediate-release tablet
FDA pathway	NDA and subsequent ANDA approvals
Therapeutic use	Short-term acute pain
Controlled-substance status	Schedule II
Typical treatment limit	No more than 10 days under the reference labeling
Biosimilar pathway	Not applicable
Generic pathway	Abbreviated New Drug Application
Orange Book relevance	Reference-listing and patent/exclusivity records govern ANDA strategy

The combination has no biologic component and does not create a biosimilar opportunity. A competitor generally pursues an ANDA demonstrating pharmaceutical equivalence and bioequivalence to the reference product, subject to applicable labeling, controlled-substance, manufacturing and facility requirements (FDA, 2015).

What excipients are used in hydrocodone and ibuprofen tablets?

Commercial formulations typically use conventional oral solid-dose excipients. The strategic objective is not to introduce novel excipients but to optimize powder flow, content uniformity, tablet strength, disintegration, dissolution, stability and manufacturability.

Typical excipient classes include:

Excipient class	Commercial function	Relevance to this combination
Microcrystalline cellulose	Diluent and dry-binder	Supports tablet hardness and content uniformity
Pregelatinized starch or other starches	Binder and disintegrant	Helps balance compactability with rapid release
Croscarmellose sodium	Superdisintegrant	Supports immediate disintegration
Povidone	Binder	Useful when direct compression is inadequate
Colloidal silicon dioxide	Glidant and moisture-control aid	Improves powder flow and blend uniformity
Magnesium stearate	Lubricant	Reduces ejection force but can slow dissolution if overused
Film-coating polymers	Protection, appearance and swallowability	Can reduce friability and improve handling
Opacifiers and colorants	Product identification	Important for controlled-substance diversion controls and visual differentiation

The precise excipient system should be selected through development work rather than copied from a label. Hydrocodone is present at a low dose relative to the tablet mass, creating a content-uniformity challenge. Ibuprofen is present at a substantially higher mass and can affect blend segregation, tablet compression and dissolution.

How should the excipient strategy address low-dose hydrocodone?

Low-dose hydrocodone creates the main formulation risk. The process must distribute a small quantity of opioid uniformly through a much larger ibuprofen-containing blend.

Direct compression

Direct compression is commercially attractive because it reduces unit operations, solvent use and drying costs. It requires excipients with consistent particle size, density and flow. A carrier system based on microcrystalline cellulose, pregelatinized starch and a controlled-glidant level can support uniformity if the active ingredients are properly milled and deagglomerated.

The principal risks are segregation during hopper transfer, sampling bias, lubricant overmixing and variable tablet weight. Continuous manufacturing may improve control, but the opioid material balance and reconciliation requirements are demanding.

Wet granulation

Wet granulation can reduce segregation and improve content uniformity by embedding hydrocodone and ibuprofen into a more uniform granule. It also can improve tablet compression when the active powders have poor flow or compactability.

The disadvantages are higher processing cost, potential hydrocodone migration during wet processing, longer development time and greater exposure to moisture. Ibuprofen's hydrophobicity can complicate wetting and dissolution.

Dry granulation

Roller compaction can provide a compromise between direct compression and wet granulation. It avoids aqueous processing and can improve flow, density and compression performance. The process must control fines generation, ribbon density and granule size because excessive densification can delay disintegration.

What formulation patents could protect hydrocodone and ibuprofen products?

The active-ingredient combination is mature, so the strongest commercial IP opportunities generally concern formulation and manufacturing features rather than composition-of-matter rights.

Potential claim categories include:

1. A specific immediate-release excipient ratio that produces defined dissolution and content-uniformity results.
2. A granulation process that limits hydrocodone segregation or migration.
3. A tablet architecture that improves mechanical strength without delaying ibuprofen release.
4. A coating system that reduces friability, moisture uptake or opioid powder loss.
5. A tamper-resistant or abuse-deterrent formulation.
6. A manufacturing process with validated opioid containment and recovery controls.
7. A multiparticulate or orally disintegrating presentation.
8. A formulation that reduces ibuprofen-related gastric irritation while retaining rapid analgesic onset.

Patent strength depends on reproducible technical effects. A claim directed only to routine excipient substitution is vulnerable to obviousness challenges. A stronger application would connect a defined composition or process to measured results, such as superior content uniformity, dissolution stability, tablet robustness or reduced abuse potential.

An excipient patent does not automatically create regulatory exclusivity. Generic applicants may design around the claims, challenge them through Paragraph IV certification, or rely on a different formulation that remains bioequivalent to the reference product.

When does hydrocodone bitartrate and ibuprofen lose exclusivity?

The product is already in the post-exclusivity generic market. Its primary commercial barrier is therefore regulatory and operational rather than remaining brand exclusivity.

Exclusivity issue	Strategic effect
New chemical entity exclusivity	No longer relevant
Reference-product exclusivity	Expired for the mature Vicoprofen product
Active-ingredient patent estate	Limited practical significance for current generic entry
Formulation patents	Potentially relevant only if unexpired and listed or enforceable
ANDA competition	Established pathway
Controlled-substance requirements	Continuing barrier to entry
REMS and opioid labeling	Ongoing compliance burden
State opioid restrictions	Commercial limitation on volume and prescribing

Patent expiration dates must be confirmed against the current FDA Orange Book and relevant patent records before an investment or launch decision. The Orange Book controls listed patents and exclusivity information for approved drug products, while issued patent rights may require separate review of continuation, reissue and litigation records (FDA, 2024b).

What is the Orange Book status of hydrocodone and ibuprofen?

The product is generally treated as a mature reference drug with generic competition rather than as a product protected by an active core patent barrier. The relevant Orange Book analysis should focus on:

• The current reference listed drug.
• Active and discontinued NDA records.
• Any patents listed against the reference product.
• Whether a proposed formulation would infringe a listed formulation or method-of-use patent.
• Paragraph IV certifications filed by ANDA applicants.
• Any 30-month stay triggered by patent litigation.

A generic applicant can use a Paragraph IV certification if it believes an asserted patent is invalid, unenforceable or not infringed. The brand or patent owner can file suit within the statutory period, potentially creating a 30-month stay of approval under the Hatch-Waxman framework (FDA, 2024c).

For a mature hydrocodone/ibuprofen tablet, the probability of meaningful delay from a core product patent is lower than for a recently approved branded product. Litigation risk can remain if a company develops an abuse-deterrent version, modified-release product, gastric-protective formulation or other differentiated dosage form.

Which excipient-enabled products offer commercial opportunity?

Low-cost generic immediate-release tablets

The largest volume opportunity is a compliant, low-cost immediate-release tablet with robust content uniformity and dissolution. Cost advantages can come from:

• Direct compression or efficient dry granulation.
• High-throughput tooling.
• Reduced coating weight.
• Standardized excipient sourcing.
• Dual-source qualification for critical excipients.
• Automated controlled-substance reconciliation.

The commercial constraint is price erosion from multiple ANDA suppliers. A new entrant needs either a manufacturing-cost advantage, reliable supply, differentiated packaging or a channel-specific distribution strategy.

Premium generic or authorized-generic supply

An authorized generic or contract supply arrangement can provide access to established distribution without relying solely on a new brand. The opportunity is strongest where a manufacturer can offer consistent supply, backup capacity and controlled-substance compliance.

Abuse-deterrent formulation

An abuse-deterrent tablet could command a higher strategic value, but it would require substantial development and regulatory evidence. FDA's abuse-deterrent opioid guidance addresses physical and chemical barriers, agonist/antagonist systems, aversion technologies and delivery-system approaches (FDA, 2015).

A hydrocodone/ibuprofen product presents a specific design problem: abuse-deterrent properties must not impair ibuprofen dissolution or create unsafe exposure after manipulation. A formulation that deters crushing but releases excessive ibuprofen under altered conditions could create a new safety risk.

Orally disintegrating or multiparticulate dosage forms

An orally disintegrating tablet could improve administration for patients with swallowing difficulty, but taste masking and opioid diversion controls become central. Multiparticulates could improve dose uniformity and permit flexible encapsulation, but they add manufacturing and packaging complexity.

Gastric-tolerability positioning

Ibuprofen carries gastrointestinal, renal and cardiovascular risks. An excipient system that reduces local gastric exposure, improves dispersion or supports a protective coating could create differentiation. The product would still need to preserve the immediate-release performance expected for an acute-pain combination. A true gastroprotective claim would likely require clinical evidence and could create a new method-of-use or combination-product development program.

What manufacturing and IP barriers affect market entry?

The most material barriers are operational.

Controlled-substance manufacturing

Hydrocodone requires:

• DEA registration and quota management.
• Secure storage and restricted access.
• Batch-level reconciliation.
• Theft, loss and diversion controls.
• Validated cleaning procedures.
• Specialized handling for potent active pharmaceutical ingredients.
• State controlled-substance compliance.

These requirements increase fixed costs and can limit the number of viable suppliers.

Ibuprofen supply and formulation risk

Ibuprofen is available from multiple global sources, but particle size, polymorphic form, density and surface area can influence compression and dissolution. Supplier changes require comparability work and may affect the finished-product control strategy.

Bioequivalence

For an ANDA, the formulation must meet the reference product's pharmaceutical-equivalence and bioequivalence requirements. Excipient changes are possible, but they cannot compromise dissolution, dose uniformity, stability or clinical performance. The opioid component also raises scrutiny around dose accuracy and abuse potential.

Packaging

Unit-dose blister packaging can improve dose control, tamper evidence, inventory reconciliation and diversion monitoring. Bottles are less expensive but may provide weaker unit-level accountability. Child-resistant and senior-friendly features must be balanced, particularly for short-term outpatient prescriptions.

How strong is the patent estate for hydrocodone and ibuprofen?

The core patent estate is commercially weak relative to new branded pharmaceuticals because the active ingredients and combination have been marketed for decades. The stronger opportunity is a narrow formulation or process patent supported by unexpected technical data.

IP category	Relative opportunity	Main vulnerability
Active ingredients	Low	Mature compounds and known therapeutic use
Basic fixed-dose combination	Low	Prior art and established product
Standard excipient substitution	Low	Obviousness and design-around risk
Low-dose content-uniformity process	Moderate	Enablement and obviousness challenges
Abuse-deterrent formulation	Moderate to high	Development cost and proof of deterrence
Gastric-protective delivery system	Moderate	Clinical and bioequivalence burden
Manufacturing containment process	Moderate	Trade-secret protection may be stronger than patent protection
Packaging and diversion controls	Low to moderate	Easy design-around in many cases

Trade secrets may provide more practical value than patents for blend order, granulation parameters, environmental controls, opioid recovery procedures and process analytical technology.

What litigation and Paragraph IV risks exist?

The mature generic market usually shifts litigation from basic product claims to narrower issues:

• Whether a formulation patent is valid and infringed.
• Whether a modified product remains bioequivalent.
• Whether an abuse-deterrent feature is covered by listed claims.
• Whether a method-of-use patent is relevant to the proposed label.
• Whether a manufacturing process creates infringement exposure.
• Whether a settlement restricts launch timing or supply rights.

Any Paragraph IV assessment must review current FDA Orange Book listings, ANDA litigation complaints, court dockets and settlement terms. A historical patent dispute involving the original product should not be treated as a current launch barrier without confirmation of the patent's expiration, terminal disclaimer, prosecution history and enforceability.

How does hydrocodone and ibuprofen compare with hydrocodone and acetaminophen?

Hydrocodone/ibuprofen has a different risk and commercial profile from hydrocodone/acetaminophen.

Factor	Hydrocodone/ibuprofen	Hydrocodone/acetaminophen
Non-opioid component	NSAID	Acetaminophen
Main dose-limiting concern	Gastrointestinal, renal and cardiovascular toxicity	Hepatotoxicity
Typical differentiation	Acute inflammatory pain	Broad acute pain use
Excipient challenge	Hydrophobic ibuprofen and low-dose hydrocodone uniformity	Blend uniformity and acetaminophen loading
Product opportunity	Short-course inflammatory pain	Larger established generic market
Abuse-deterrent development	Must preserve ibuprofen release	Must preserve acetaminophen release
Regulatory concern	NSAID boxed-warning and contraindication language	Acetaminophen total daily exposure

The ibuprofen combination may be attractive for selected acute inflammatory pain indications, but the total addressable market is narrower than the broader hydrocodone/acetaminophen category. Regulatory and commercial teams must also account for non-opioid alternatives, state prescribing limits and declining opioid utilization.

What is the revenue exposure and generic launch outlook?

Revenue exposure is concentrated in short-duration prescriptions and institutional or outpatient channels. The mature product has limited protection against price competition. A generic launch can proceed where the applicant has:

1. An approved or approvable ANDA.
2. Adequate hydrocodone quota.
3. DEA-compliant manufacturing and distribution.
4. Reliable ibuprofen and excipient supply.
5. A validated commercial-scale process.
6. A controlled-substance quality system.
7. Packaging and labeling aligned with FDA requirements.

The most credible launch scenarios are:

• A low-cost conventional tablet entering an established generic market.
• A supply-constrained entrant with dependable controlled-substance capacity.
• An authorized-generic arrangement.
• A differentiated formulation targeting swallowing, tamper resistance or tolerability.
• A contract manufacturing platform serving multiple opioid combination products.

A conventional tablet is unlikely to sustain premium pricing without a supply, channel or clinical differentiation. A formulation with defensible IP can support better economics, but the development and regulatory burden rises sharply.

Key Takeaways

• Hydrocodone bitartrate and ibuprofen is a mature FDA-approved immediate-release combination, commonly supplied at 7.5 mg/200 mg.
• The commercial opportunity is primarily generic manufacturing, authorized-generic supply, contract development and excipient-enabled differentiation.
• Low-dose hydrocodone content uniformity is the central formulation challenge.
• Direct compression offers the lowest manufacturing cost; dry or wet granulation can improve uniformity and tablet performance.
• Standard excipient substitutions have limited patent strength unless supported by unexpected technical results.
• Abuse-deterrent, gastric-tolerability and specialty dosage forms offer greater differentiation but require more development evidence.
• Core exclusivity is no longer the principal barrier. DEA controls, quota, manufacturing security, bioequivalence and supply reliability are more important.
• Paragraph IV risk depends on current Orange Book listings and any live formulation or method-of-use patents.
• The product has no biosimilar opportunity because it is a small-molecule oral tablet.
• Generic launch economics are likely to depend on cost control, dependable supply and regulatory execution.

FAQs

Can a new hydrocodone and ibuprofen tablet use different excipients from Vicoprofen?

Yes. An ANDA applicant can use different inactive ingredients if the product meets applicable pharmaceutical-equivalence, bioequivalence, dissolution, stability and safety requirements.

Can ibuprofen particle size create patent protection?

Particle size alone usually provides weak protection unless it produces a demonstrated and non-obvious technical result, such as improved dissolution, reduced variability or superior stability.

Is an abuse-deterrent hydrocodone/ibuprofen product eligible for premium pricing?

Potentially, but premium pricing would depend on FDA-recognized abuse-deterrent performance, prescriber adoption, payer treatment and the strength of any formulation IP. The product must also preserve ibuprofen release and safety.

Does the opioid component require special excipient testing?

The excipients themselves are not automatically subject to opioid-specific testing, but the formulation requires tight control of hydrocodone assay, content uniformity, degradation, dissolution, cleaning validation and material reconciliation.

Can a manufacturer protect the formulation as a trade secret instead of using patents?

Yes. Granulation order, blend parameters, containment methods, process controls and recovery procedures may be more valuable as trade secrets when competitors can design around broad formulation claims.

References

1. U.S. Food and Drug Administration. (2015). Abuse-deterrent opioids: Evaluation and labeling guidance for industry. https://www.fda.gov
2. U.S. Food and Drug Administration. (2015). Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. https://www.fda.gov
3. U.S. Food and Drug Administration. (2024a). Hydrocodone bitartrate and ibuprofen tablets: Prescribing information. https://www.accessdata.fda.gov
4. U.S. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov
5. U.S. Food and Drug Administration. (2024c). ANDA submissions: Content and format of an ANDA. https://www.fda.gov
6. U.S. Drug Enforcement Administration. (2024). Controlled substances schedules and quota regulations. https://www.deadiversion.usdoj.gov