List of Excipients in Branded Drug HYDROCODONE BITARTRATE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Persion Pharmaceuticals LLC	HYDROCODONE BITARTRATE	hydrocodone bitartrate	65224-910	AMMONIO METHACRYLATE COPOLYMER TYPE B
Persion Pharmaceuticals LLC	HYDROCODONE BITARTRATE	hydrocodone bitartrate	65224-910	FD&C BLUE NO. 1
Persion Pharmaceuticals LLC	HYDROCODONE BITARTRATE	hydrocodone bitartrate	65224-910	FD&C RED NO. 3
Persion Pharmaceuticals LLC	HYDROCODONE BITARTRATE	hydrocodone bitartrate	65224-910	FD&C RED NO. 40

Generic Drugs Containing HYDROCODONE BITARTRATE

Company	Ingredient	NDC	Excipient
Alvogen Inc	hydrocodone bitartrate	47781-392	AMMONIA
Alvogen Inc	hydrocodone bitartrate	47781-392	BUTYL ALCOHOL
Alvogen Inc	hydrocodone bitartrate	47781-392	CELLULOSE, MICROCRYSTALLINE
Alvogen Inc	hydrocodone bitartrate	47781-392	FERROSOFERRIC OXIDE

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

# Of NDCs	Excipient
1	AMMONIA
1	AMMONIO METHACRYLATE COPOLYMER TYPE B
2	BUTYL ALCOHOL
3	CELLULOSE, MICROCRYSTALLINE

Last updated: August 22, 2026

ecutive summary: Hydrocodone bitartrate offers the strongest excipient-driven opportunities in extended-release abuse-deterrent tablets, low-cost immediate-release generics, and differentiated combination products. The commercial value is concentrated in formulation performance: controlled release, tamper resistance, dose uniformity, moisture stability, and efficient manufacturing. Hydrocodone is a Schedule II opioid, so excipient innovation must satisfy FDA bioequivalence, abuse-deterrence, controlled-substance, and labeling requirements. The largest barriers are clinical safety scrutiny, limited market growth, opioid quota controls, and entrenched generic competition.

Hydrocodone Bitartrate Excipient Strategy and Commercial Opportunities

What is the commercial role of excipients in hydrocodone bitartrate products?

Excipients determine whether hydrocodone bitartrate is delivered as an immediate-release tablet, an extended-release matrix, a liquid, or a tamper-resistant dosage form. They also influence dose dumping, abuse potential, tablet robustness, dissolution, storage stability, and cost of goods.

Hydrocodone bitartrate is used in several product categories:

Product category	Representative products	Primary excipient objective
Immediate-release combination tablet	Vicodin, Norco and generic hydrocodone/acetaminophen	Fast disintegration, compressibility, low cost
Extended-release tablet	Hysingla ER, Zohydro ER	Controlled release and resistance to crushing or extraction
Oral solution or syrup	Hydrocodone-containing cough and analgesic products	Solubility, palatability, preservative protection and dosing accuracy
Abuse-deterrent formulation	Hysingla ER	Physical and chemical resistance to manipulation
Specialty solid dosage form	Potential orally disintegrating, sprinkle or multiparticulate products	Rapid administration, dose flexibility or differentiated adherence

The excipient strategy must match the regulatory pathway. A generic immediate-release tablet generally requires pharmaceutical equivalence and bioequivalence under an ANDA. A materially different release profile, abuse-deterrent design, or delivery system may require a 505(b)(2) application or a new NDA.

Which excipients are used in hydrocodone bitartrate formulations?

Common excipients include microcrystalline cellulose, lactose monohydrate, povidone, crospovidone, croscarmellose sodium, pregelatinized starch, hypromellose, colloidal silicon dioxide, magnesium stearate, polyethylene glycol, titanium dioxide and coating polymers.

Their functions differ by dosage form.

Immediate-release tablets

Immediate-release hydrocodone bitartrate combination tablets commonly use:

• Microcrystalline cellulose as a dry binder and compressibility aid.
• Lactose or other fillers to achieve tablet weight and content uniformity.
• Povidone or pregelatinized starch as a binder.
• Crospovidone or croscarmellose sodium as a superdisintegrant.
• Colloidal silicon dioxide as a glidant.
• Magnesium stearate as a lubricant.
• Film-coating polymers for appearance, identification and moisture control.

The preferred commercial design is usually a direct-compression or highly efficient wet-granulation process. The objective is a robust tablet with rapid dissolution and low manufacturing complexity.

For generic developers, excipient selection is constrained by the reference listed drug. A formulation can use different inactive ingredients, but the finished product must meet dissolution, bioequivalence, stability and labeling requirements. Hydrocodone products containing acetaminophen also require control of blend uniformity and degradation because the combination creates additional analytical and stability requirements.

Extended-release tablets

Extended-release products use hydrophilic or polymeric matrices. Hypromellose is a common release-controlling polymer because it hydrates after administration and forms a gel barrier that slows drug diffusion and erosion.

Other formulation components can include:

• High-viscosity hypromellose for matrix strength.
• Polyethylene oxide or related swellable polymers.
• Lactose or microcrystalline cellulose as fillers.
• Povidone as a binder.
• Colloidal silicon dioxide to improve powder flow.
• Magnesium stearate as a lubricant.
• Functional film coatings for identification and moisture protection.

The key development variables are polymer grade, polymer concentration, tablet hardness, porosity, drug loading, compression force and dissolution behavior across pH conditions. A formulation that releases hydrocodone too quickly can create dose-dumping and safety concerns. One that releases too slowly can produce inadequate analgesia or fail bioequivalence requirements.

What formulations are protected by hydrocodone bitartrate patents?

The most commercially relevant formulation protection has historically involved extended-release hydrocodone tablets and abuse-deterrent delivery systems rather than the hydrocodone molecule itself.

Hysingla ER is an extended-release hydrocodone bitartrate tablet approved by FDA in 2014. Its product design uses a polymer-based tablet intended to resist common forms of manipulation, including crushing. Zohydro ER, approved in 2013, was an extended-release hydrocodone product without acetaminophen. FDA product labeling identifies the inactive ingredients used in each marketed dosage form.[1,2]

Patent protection in this area can cover:

• Polymer matrix composition.
• Drug-to-polymer ratios.
• Tablet hardness and physical properties.
• Manufacturing processes.
• Abuse-deterrent performance.
• Dissolution profiles.
• Multiparticulate or coated-particle designs.
• Methods of treating pain with the formulation.
• Specific strength and dosage-form combinations.

The basic hydrocodone compound has long been known. Commercial patent value therefore depends on formulation claims, manufacturing claims and method-of-use claims. Patent estates for extended-release opioid products may also include continuation applications and overlapping claims that complicate generic launch timing.

When does hydrocodone bitartrate lose exclusivity?

Hydrocodone bitartrate immediate-release products have been generic for many years. Their commercial protection is generally based on manufacturing scale, supply reliability, customer contracts and regulatory compliance rather than meaningful molecule-level exclusivity.

Milestone	Hydrocodone relevance
Hydrocodone combination products	Long-established products with substantial generic competition
Zohydro ER approval	October 2013
Hysingla ER approval	November 2014
Three-year clinical-investigation exclusivity	Historically relevant for the extended-release approvals, but expired
Patent exclusivity	Product-specific and dependent on Orange Book-listed claims
Generic entry	Available for multiple immediate-release products; extended-release entry depends on formulation and patent status

The three-year exclusivity associated with new clinical investigations for the extended-release products has expired. The remaining commercial barrier is product-specific patent protection, regulatory complexity and the technical difficulty of reproducing an extended-release or abuse-deterrent profile.

The FDA Orange Book identifies approved drug products and listed patents for applicable NDA products. NDA 202880 is associated with Zohydro ER, and NDA 206627 is associated with Hysingla ER.[3] Orange Book status can change through patent-listing updates, delisting, litigation outcomes and regulatory actions.

What is the Orange Book and Paragraph IV status of hydrocodone products?

Immediate-release hydrocodone/acetaminophen products are primarily ANDA products and are not protected by a new-molecule exclusivity period. The relevant competitive process is ordinary ANDA approval, subject to any listed patents and regulatory requirements.

For extended-release NDA products, an ANDA applicant may file:

• Paragraph I certification if no patent is listed.
• Paragraph II certification if the patent has expired.
• Paragraph III certification if the applicant will wait until patent expiration.
• Paragraph IV certification if the applicant asserts that the patent is invalid, unenforceable or not infringed.

A Paragraph IV filing can trigger patent litigation under the Hatch-Waxman Act. A timely lawsuit may impose a 30-month stay on approval, subject to statutory exceptions and court developments.[4]

The most important diligence points are:

1. Current Orange Book patent listings for the reference product.
2. Patent expiration dates and pediatric extensions.
3. Whether the listed claims cover the proposed dosage form.
4. Whether a formulation patent is vulnerable to non-infringing design-around.
5. Whether the generic applicant has a Paragraph IV certification.
6. Whether any settlement restricts launch timing or product design.

How strong is the patent estate for hydrocodone bitartrate extended-release products?

A hydrocodone extended-release patent estate can be commercially meaningful when claims cover the product's release mechanism and abuse-deterrent performance rather than only a broad list of excipients.

Stronger claim types

Claims are generally more defensible when they specify:

• Defined polymer viscosity or molecular-weight ranges.
• Quantified release limits across multiple dissolution conditions.
• Resistance to crushing, grinding or solvent extraction.
• A narrow drug-to-polymer ratio.
• A manufacturing process that produces a distinctive matrix structure.
• Correlation between physical properties and pharmacokinetic performance.

Weaker claim types

Risk is higher when claims cover:

• Conventional excipients at broad concentrations.
• Routine tablet coatings.
• Generic sustained-release concepts.
• Functional language without clear structural limitations.
• Formulations that can be reproduced with ordinary polymer substitution.

A generic company may design around a patent by changing polymer grade, matrix composition, granulation method, coating architecture or tablet geometry while preserving bioequivalence. That creates a central commercial question: whether the patent protects the active formulation concept or only one implementation.

What excipient strategies create the best commercial opportunities?

1. Abuse-deterrent extended-release tablets

This is the highest-value excipient opportunity. A commercial formulation can combine a high-viscosity hydrophilic matrix with a tablet structure that resists pulverization and limits rapid extraction.

Potential technologies include:

• High-strength polymer matrices.
• Swellable polymers that form viscous gels.
• Matrix systems that become difficult to syringe after water addition.
• Coated drug particles embedded in a compressed matrix.
• Multilayer tablets with distinct release zones.
• Thermoplastic or melt-processed matrices.
• Aversive excipients, subject to safety and labeling review.

FDA's abuse-deterrent guidance evaluates physical and chemical manipulation, pharmacokinetic effects and real-world abuse potential. A formulation may receive abuse-deterrent labeling only if the evidence supports the applicable FDA category.[5]

2. Low-cost immediate-release generic platforms

Immediate-release hydrocodone products offer lower technical risk and faster development than abuse-deterrent products. The opportunity is operational rather than scientifically novel.

A competitive platform should provide:

• Direct compression or low-step granulation.
• Fast disintegration across commercial strengths.
• Low lubricant sensitivity.
• Stable tablet hardness.
• Low friability.
• Efficient coating.
• Flexible sourcing of lactose, cellulose and superdisintegrants.
• A manufacturing process compatible with controlled-substance security requirements.

The best target customers are generic manufacturers seeking reliable supply, contract development and manufacturing organizations, and companies with existing opioid distribution infrastructure.

3. Hydrocodone/acetaminophen combination products

Combination products remain commercially relevant but carry a distinct safety profile. Acetaminophen exposure limits constrain dosing and may create demand for lower-acetaminophen or acetaminophen-free hydrocodone products.

Excipient opportunities include:

• Improved moisture protection.
• Reduced tablet size.
• Faster disintegration without excessive friability.
• Bilayer or multilayer tablets.
• Taste-masked liquid formulations.
• Unit-dose packaging that supports controlled dispensing.

Any reformulation that changes dose, release profile or clinical use can affect the regulatory pathway and labeling.

4. Oral liquids and pediatric-oriented delivery systems

Hydrocodone oral liquids require careful control of solubility, taste, viscosity, preservative compatibility and dose measurement. The market is constrained by opioid safety concerns, but specialized opportunities can exist in hospital, palliative-care and medically supervised settings.

Relevant excipient systems include:

• Sweetener and flavor combinations.
• Viscosity modifiers.
• Preservatives compatible with hydrocodone bitartrate.
• Buffer systems.
• Child-resistant, unit-dose packaging.
• Metered oral syringes and dosing adapters.

A liquid formulation must control concentration uniformity and minimize dosing errors. High-viscosity systems may improve handling but can create container-closure and dose-delivery problems.

What regulatory barriers affect hydrocodone excipient development?

Hydrocodone is a Schedule II controlled substance under the federal Controlled Substances Act. Manufacturers must comply with DEA registration, security, recordkeeping, inventory and production quota requirements.[6]

FDA development issues include:

• ANDA pharmaceutical-equivalence requirements.
• Comparative dissolution testing.
• Bioequivalence for immediate-release products.
• Partial or full replicate designs where appropriate.
• Abuse-deterrence testing for relevant claims.
• Extractables and leachables assessment.
• Nitrosamine and elemental-impurity control.
• Stability under ICH conditions.
• Excipient safety and route-of-administration precedent.
• Child-resistant packaging and medication-error controls.

The use of a novel excipient can create a regulatory advantage if it improves performance, but it may also increase review time and toxicology requirements. A familiar excipient supported by extensive oral solid-dosage precedent is usually easier to commercialize.

Which companies are positioned in the hydrocodone bitartrate market?

The competitive field includes branded NDA holders, generic pharmaceutical companies, opioid-focused manufacturers and contract manufacturers.

Company type	Commercial position
Branded NDA holder	Owns product label, formulation know-how and any remaining patents
Large generic manufacturer	Competes on cost, supply continuity and pharmacy access
Specialty controlled-substance manufacturer	Uses DEA infrastructure and compliance capability
CDMO	Develops, manufactures or packages controlled-substance products
Excipient supplier	Provides polymers, binders, coatings or abuse-deterrent platforms
Licensing company	Offers formulation patents or proprietary matrix technology

Companies with existing controlled-substance facilities have an advantage because DEA compliance and secure handling can be costly. Excipient suppliers can monetize the market through platform licensing, formulation development, technical support and supply agreements.

What licensing deals and partnership models are available?

The most practical licensing structures involve a formulation platform rather than hydrocodone API alone.

Potential deal models include:

1. An excipient supplier licenses a polymer matrix technology to a generic manufacturer.
2. A CDMO develops a hydrocodone extended-release product under a co-development agreement.
3. A patent holder grants a field-limited license for hydrocodone abuse-deterrent use.
4. A generic company licenses a ready-to-file ANDA formulation.
5. A manufacturer obtains dual-source rights for critical polymers and coating materials.
6. A branded company licenses a reformulated hydrocodone product for a defined geography.

Deal value depends on patent life, regulatory readiness, bioequivalence risk, controlled-substance manufacturing capacity and the probability of generic entry. A platform that applies to oxycodone, morphine and hydromorphone may command greater value than a hydrocodone-only formulation.

What generic launch risks exist for hydrocodone bitartrate?

Generic launch risk is highest for extended-release products and lowest for conventional immediate-release tablets.

Risk	Immediate-release product	Extended-release product
Bioequivalence failure	Moderate	High
Formulation patent challenge	Low to moderate	High
Dissolution variability	Moderate	High
Abuse-deterrence requirement	Usually limited	Material
Manufacturing complexity	Low	High
Controlled-substance quota risk	High	High
Price erosion after entry	High	Moderate to high
Supply-chain disruption	Moderate	High

Commercial success depends on more than FDA approval. Wholesaler acceptance, pharmacy stocking, DEA quota availability, product liability exposure, state opioid restrictions and payer coverage can determine actual launch economics.

How does hydrocodone compare with competing opioid formulations?

Hydrocodone competes with oxycodone, morphine, tramadol and buprenorphine products. Immediate-release hydrocodone/acetaminophen has historically benefited from broad prescribing familiarity, but acetaminophen exposure limits its dose flexibility. Hydrocodone extended-release products compete with oxycodone extended-release and other long-acting opioid products.

From an excipient perspective:

• Hydrocodone/acetaminophen favors low-cost immediate-release tablets.
• Acetaminophen-free hydrocodone favors extended-release and specialty formulations.
• Oxycodone has a broader established market for extended-release and abuse-deterrent products.
• Buprenorphine offers different pharmacology and delivery opportunities, including sublingual and transdermal systems.
• Tramadol competes in lower-potency pain markets with a different safety and regulatory profile.

Hydrocodone's strongest formulation opportunity is a robust, abuse-deterrent extended-release tablet with defensible manufacturing claims and reliable controlled-substance supply.

What is the FDA regulatory status of hydrocodone bitartrate?

FDA has approved hydrocodone bitartrate in immediate-release combination products, oral liquid products and extended-release tablets. Hysingla ER was approved in 2014 as an extended-release hydrocodone bitartrate tablet with abuse-deterrent properties. Zohydro ER was approved in 2013 as an extended-release hydrocodone product without acetaminophen.[1,2]

There is no biosimilar pathway for hydrocodone bitartrate because it is a chemically synthesized small molecule. Competition proceeds through ANDAs, 505(b)(2) applications and NDAs, depending on the formulation and labeling differences.

Key Takeaways

• Immediate-release hydrocodone bitartrate products are mature generic markets with limited molecule-level exclusivity.
• Extended-release and abuse-deterrent formulations offer the highest excipient-driven value.
• Hypromellose, polyethylene oxide, microcrystalline cellulose, lactose, povidone and superdisintegrants are central formulation tools.
• Patent value is concentrated in matrix composition, release performance, tamper resistance and manufacturing processes.
• Hysingla ER and Zohydro ER are the main FDA-approved extended-release hydrocodone reference products.
• Novel excipients can improve differentiation but create regulatory and toxicology burdens.
• DEA quota, security and controlled-substance compliance are material barriers to entry.
• Generic launch risk is driven by bioequivalence, dissolution, patent litigation, quota access and post-launch price erosion.
• The most attractive commercial model is a scalable abuse-deterrent polymer platform that can be licensed across multiple Schedule II opioids.

FAQs

Can hydrocodone bitartrate be formulated as an orally disintegrating tablet?

Yes. An orally disintegrating tablet could use mannitol, crospovidone, low-substituted hydroxypropyl cellulose and taste-masking technology. The product would require careful control of opioid abuse risk, dose uniformity, mechanical strength and bioequivalence.

Which excipient is most important for hydrocodone extended release?

High-viscosity hypromellose or a comparable swellable polymer is often central to a hydrophilic matrix system. Commercial performance depends on the full formulation and manufacturing process, not on one excipient alone.

Can a generic company use different excipients from Hysingla ER?

Yes, provided the proposed product satisfies FDA requirements for pharmaceutical equivalence, bioequivalence, dissolution, stability and labeling. A different excipient system may also create patent design-around opportunities.

Is an abuse-deterrent hydrocodone formulation automatically preferred by FDA?

No. FDA evaluates the evidence supporting specific abuse-deterrent claims. Physical resistance alone does not establish that a product prevents abuse or addiction.[5]

Are hydrocodone bitartrate excipient patents commercially valuable after generic entry?

They can be valuable when they cover a difficult-to-reproduce release mechanism, abuse-deterrent property or manufacturing process. Broad claims to conventional fillers, binders or lubricants generally provide weaker protection.

References

1. U.S. Food and Drug Administration. (2013). Zohydro ER prescribing information. FDA/DailyMed.

2. U.S. Food and Drug Administration. (2014). Hysingla ER prescribing information. FDA/DailyMed.

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

4. U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and generic drug patent certifications. FDA.

5. U.S. Food and Drug Administration. (2015). Guidance for industry: Abuse-deterrent opioids: Evaluation and labeling. FDA.

6. U.S. Drug Enforcement Administration. (n.d.). Controlled substances act and drug scheduling. U.S. Department of Justice.

7. U.S. Pharmacopeial Convention. (2023). United States Pharmacopeia and National Formulary. USP.

8. International Council for Harmonisation. (2003). Q1A(R2): Stability testing of new drug substances and products. ICH.