List of Excipients in Branded Drug TYLENOL WITH CODEINE

Generic Drugs Containing TYLENOL WITH CODEINE

Company	Ingredient	NDC	Excipient
A-S Medication Solutions	acetaminophen and codeine phosphate	50090-0006	MAGNESIUM STEARATE
A-S Medication Solutions	acetaminophen and codeine phosphate	50090-0006	POWDERED CELLULOSE
A-S Medication Solutions	acetaminophen and codeine phosphate	50090-0006	SODIUM METABISULFITE
A-S Medication Solutions	acetaminophen and codeine phosphate	50090-0006	STARCH, CORN

What are the Most Frequently-Used Excipients in TYLENOL WITH CODEINE?

# Of NDCs	Excipient
1	MAGNESIUM STEARATE
1	POWDERED CELLULOSE
1	SODIUM METABISULFITE
1	STARCH, CORN

TYLENOL WITH CODEINE Excipient Strategy and Commercial Opportunities

Last updated: August 11, 2026

TYLENOL WITH CODEINE is an immediate-release oral combination of acetaminophen and codeine. Its commercial value is concentrated in formulation reliability, palatability, dose flexibility, abuse-deterrent packaging, and regulatory positioning rather than in novel active-ingredient protection. The product has limited apparent patent differentiation because acetaminophen and codeine are established active ingredients and generic competition is extensive. Excipient innovation can still support line extensions, lifecycle management, contract manufacturing, and differentiated generic products.

What is TYLENOL WITH CODEINE and how is it formulated?

TYLENOL WITH CODEINE products combine acetaminophen with codeine phosphate. The principal tablet strengths historically associated with the brand are:

Product designation	Acetaminophen per tablet	Codeine phosphate per tablet	Typical commercial role
No. 1	300 mg	7.5 mg	Lower opioid exposure
No. 2	300 mg	15 mg	Moderate analgesia
No. 3	300 mg	30 mg	Standard prescription strength
No. 4	300 mg	60 mg	Higher codeine exposure

Oral solution products have also been marketed with lower concentrations per 5 mL, including formulations containing approximately 120 mg acetaminophen and 12 mg codeine phosphate per 5 mL. Exact strengths, inactive ingredients, and availability depend on the manufacturer and National Drug Code.

The core formulation challenge is balancing three variables:

1. Acetaminophen dose uniformity and chemical stability.
2. Codeine content uniformity at relatively low dose levels.
3. Patient acceptability without encouraging excessive dosing or misuse.

The product is generally an immediate-release dosage form. This limits the commercial value of conventional extended-release excipient systems unless the sponsor develops a distinct product under a new regulatory pathway.

What excipients are used in TYLENOL WITH CODEINE tablets and oral solutions?

Inactive ingredients vary by manufacturer. Common tablet excipient categories include:

Excipient function	Typical materials	Commercial purpose
Diluent	Microcrystalline cellulose, lactose, starch, dibasic calcium phosphate	Tablet mass and content uniformity
Binder	Povidone, pregelatinized starch, hydroxypropyl cellulose	Mechanical strength
Disintegrant	Crospovidone, croscarmellose sodium, sodium starch glycolate	Rapid breakup after ingestion
Lubricant	Magnesium stearate, stearic acid	Manufacturing flow and ejection
Glidant	Colloidal silicon dioxide	Powder-flow improvement
Coating	Hypromellose, polyethylene glycol, titanium dioxide, colorants	Identification, swallowability, moisture control
Taste modifier	Sweeteners, flavors, film coatings	Reduction of bitter opioid taste
Solution preservative	Sodium benzoate or related systems	Microbial control
Solution vehicle	Purified water, glycerin, sorbitol, propylene glycol	Solubilization and mouthfeel

Oral solutions require tighter control of pH, preservative efficacy, microbial quality, viscosity, and flavor masking. Acetaminophen has limited water solubility, while codeine phosphate is more soluble. This creates a formulation tradeoff between concentration, precipitation risk, and acceptable oral volume.

A sponsor should treat the reference product's inactive-ingredient profile as a starting point rather than as a target. Generic approval depends on pharmaceutical equivalence, bioequivalence, quality, labeling, and applicable inactive-ingredient requirements. A different excipient system can be commercially useful if it maintains performance and supports a meaningful product attribute.

What excipient strategies can differentiate TYLENOL WITH CODEINE?

Can taste masking create a commercial advantage?

Yes, particularly for oral solutions and patients with swallowing difficulties. Codeine has a bitter taste, and acetaminophen can contribute to an unpleasant aftertaste. Potential approaches include:

• Polymer coating of drug particles.
• Ion-exchange resin complexes.
• Cyclodextrin complexation.
• pH-controlled flavor masking.
• High-intensity sweetener systems.
• Fruit or mint flavor systems.
• Viscosity adjustment to reduce rapid exposure to taste receptors.

Taste masking must not materially delay codeine release or produce inconsistent dosing. Resin complexes and coated particles are more likely to create regulatory and dissolution complexity than conventional sweetener-flavor systems.

The strongest commercial opportunity is a well-tolerated, low-volume, dye-free oral solution with reliable dosing and improved palatability. This could support pharmacy dispensing, post-procedure use, and patients who cannot swallow tablets.

Can sugar-free and alcohol-free formulations expand the market?

Yes. Sugar-free formulations can target patients with diabetes, dental-risk concerns, and long-term medication restrictions. Alcohol-free formulations can address caregiver preference, pediatric safety concerns, and institutional formulary requirements.

The formulation must manage the consequences of removing sucrose or ethanol:

• Sorbitol, glycerin, or other polyols can change viscosity and cause gastrointestinal effects.
• Preservative performance can decline when ethanol is removed.
• Flavor solubilization becomes more difficult.
• High-intensity sweeteners may create an aftertaste.
• Oral-solution density can affect dose measurement.

An alcohol-free, sugar-free product with a calibrated oral syringe and child-resistant packaging has greater commercial relevance than a simple flavor change.

Can abuse-deterrent excipients support premium positioning?

Potentially, but the regulatory and clinical burden is high. Abuse-deterrent strategies may include:

• Increased gel formation when crushed and mixed with liquid.
• Physical barriers to crushing.
• Sequestering of opioid through ion-exchange or polymer systems.
• Nasal-irritant or aversive components.
• Packaging designed to restrict access.

A tablet that resists crushing is not automatically an FDA-recognized abuse-deterrent product. FDA labeling claims require evidence under the agency's abuse-deterrent guidance and may require comparative laboratory, pharmacokinetic, clinical abuse-potential, or postmarketing data.[1]

The commercial case is strongest for institutional buyers, opioid stewardship programs, and branded or authorized-generic positioning. The added manufacturing cost and potential impact on dissolution may limit broad generic adoption.

What formulation patents could protect a TYLENOL WITH CODEINE product?

The active ingredients themselves offer little practical new-patent opportunity. Protection would more likely arise from:

• A novel taste-masked codeine particle.
• A specific resin complex.
• A stable concentrated oral solution.
• A low-volume dosing system.
• A novel preservative combination.
• A tamper-resistant tablet.
• A multiparticulate dosage form.
• A particular excipient ratio tied to dissolution or stability.
• A combination of formulation and method of use.

Patentability requires more than substituting one conventional excipient for another. A defensible claim should connect the composition to a measurable technical result, such as improved stability, reduced bitterness, controlled codeine release, reduced extractability, or a defined dissolution profile.

A formulation patent is more valuable when the commercial product requires the claimed feature. Broad claims to routine binders, lubricants, colors, or sweeteners are vulnerable to invalidity challenges based on anticipation, obviousness, or lack of technical effect.

How many patents cover TYLENOL WITH CODEINE?

No single patent count applies across all TYLENOL WITH CODEINE products. The brand includes multiple strengths, dosage forms, manufacturers, and historical product records. Patent exposure must be assessed by the specific NDA, ANDA, formulation, and jurisdiction.

For an immediate-release acetaminophen/codeine product, the practical barriers are more likely to involve:

• FDA approval requirements.
• Controlled-substance registration and distribution controls.
• Manufacturing quality systems.
• Product liability.
• Trademark and trade dress.
• Supply-chain controls for codeine.
• State opioid prescribing rules.

The Orange Book should be reviewed for the relevant reference-listed drug and current patent or exclusivity entries. A brand name does not establish continuing patent protection, and trademark rights do not prevent approval of a therapeutically equivalent generic under a different name.[2]

When does TYLENOL WITH CODEINE lose exclusivity?

The product's principal market protections are largely historical. Acetaminophen/codeine immediate-release products have been available for decades, and multiple generic products have entered the U.S. market.

Current exclusivity analysis should separate four concepts:

Protection	Relevance to TYLENOL WITH CODEINE
New chemical entity exclusivity	Not applicable to established acetaminophen or codeine
New clinical investigation exclusivity	Possible only for qualifying new evidence and approved labeling
Orphan exclusivity	Not applicable to the conventional analgesic indication
Patent exclusivity	Product-specific and must be confirmed in current FDA records
Trademark protection	Can protect the TYLENOL brand but not the active-ingredient combination itself

Because generic acetaminophen/codeine products are already marketed, a new entrant would generally face established ANDA competition rather than a first-generic opportunity. A reformulated product with a new clinical or abuse-deterrent attribute could pursue a different commercial strategy, but the regulatory pathway would depend on the proposed claims and formulation.

What is the Orange Book status and Paragraph IV risk?

Paragraph IV litigation is generally most relevant when an ANDA applicant challenges an unexpired listed patent. For long-marketed immediate-release acetaminophen/codeine products, the primary competitive issue is usually whether any current, enforceable, Orange Book-listed patent remains relevant to the proposed product.

A sponsor launching a reformulated product should expect scrutiny of:

• Whether the patent is eligible for Orange Book listing.
• Whether the claims cover the finished dosage form.
• Whether the generic or follow-on product practices the claims.
• Whether a Paragraph IV certification is necessary.
• Whether a section viii statement can omit a patented method of use.
• Whether a 30-month stay could delay approval.

Method-of-use patents can be more important than formulation patents if a sponsor secures a new indication or dosing regimen. A generic applicant may sometimes carve out the patented use through labeling, but that approach depends on the exact claim scope and FDA labeling requirements.

What FDA regulatory issues affect commercial opportunities?

Codeine creates material safety and compliance obligations. FDA labeling includes opioid-related warnings, acetaminophen hepatotoxicity warnings, respiratory-depression risks, and restrictions concerning children and breastfeeding. FDA has warned against codeine use in children younger than 12 and in adolescents with certain risk factors after tonsillectomy or adenoidectomy.[3]

The FDA and DEA framework also affects commercialization:

• Codeine combination products are controlled substances under federal law.
• Distribution requires controlled-substance compliance.
• Manufacturing requires validated content uniformity and impurity controls.
• Acetaminophen creates a dose-related liver-toxicity risk.
• Pediatric formulations require careful measuring-device design.
• Preservative systems in oral solutions require antimicrobial effectiveness support.
• Labeling must prevent confusion among strengths.

A formulation that reduces dosing errors may have greater regulatory and commercial value than one that merely changes flavor. Examples include a fixed-dose oral syringe, strength-specific bottle geometry, color differentiation, and clear maximum daily acetaminophen instructions.

What generic entry risks exist for TYLENOL WITH CODEINE?

Generic competition is already established, so the principal risks are price erosion and product substitution. New entrants may compete through:

• Lower manufacturing cost.
• Reliable supply.
• Multiple tablet strengths.
• Dye-free or gluten-free positioning.
• Sugar-free oral solution.
• Improved taste.
• Unit-dose hospital packaging.
• Private-label pharmacy supply.
• Authorized-generic arrangements.

The main barriers are not normally patent-based. They include opioid quota availability, controlled-substance compliance, quality failures, recalls, supply interruptions, and pharmacy contracting.

A sponsor should avoid commercial claims implying superior efficacy unless supported by clinical evidence. Excipient differentiation should focus on documented quality attributes, patient usability, and operational value.

Which companies are challenging or competing with TYLENOL WITH CODEINE?

Competition comes primarily from generic manufacturers and other analgesic products rather than from biosimilar developers. Relevant competitive categories include:

Competitive category	Examples
Generic acetaminophen/codeine	Multiple ANDA-approved manufacturers
Other opioid combinations	Hydrocodone/acetaminophen, oxycodone/acetaminophen
Nonopioid analgesics	Ibuprofen, naproxen, acetaminophen alone
Local or regional products	Codeine-containing oral solutions and tablets
Hospital alternatives	Injectable analgesics and procedure-specific pain products

Biosimilar risk is not relevant because TYLENOL WITH CODEINE is a small-molecule combination drug, not a biologic. The competitive risk is generic substitution, therapeutic substitution, and opioid-prescribing restrictions.

What licensing and partnership opportunities exist?

Licensing opportunities are most credible in formulation technology and distribution rather than in the active ingredients. Potential structures include:

1. A formulation license for taste masking or abuse deterrence.
2. A contract manufacturing agreement for tablets or oral solutions.
3. A private-label supply deal with a pharmacy or hospital distributor.
4. An authorized-generic arrangement with a brand owner.
5. A regional licensing agreement for controlled-substance distribution.
6. A device partnership for unit-dose oral delivery.

The most attractive asset would combine an issued formulation patent, reproducible scale-up, acceptable dissolution, and a clear regulatory pathway. A formulation without enforceable IP or a cost advantage is unlikely to support substantial royalty economics in an already genericized market.

How strong is the patent estate for TYLENOL WITH CODEINE?

The estate is likely weak for conventional immediate-release tablets and stronger only where a sponsor has developed a genuinely differentiated formulation. Patent strength depends on:

• Claim breadth.
• Demonstrated technical effect.
• Freedom-to-operate against prior art.
• Orange Book eligibility.
• Ease of designing around the claims.
• Commercial necessity of the claimed excipient system.
• Remaining patent term.

A practical diligence conclusion is that conventional tablet excipient selection offers limited defensibility. A concentrated, alcohol-free, sugar-free oral solution, a validated taste-masked multiparticulate system, or a documented abuse-deterrent dosage form offers greater potential for patent and commercial differentiation.

What commercial strategy offers the best opportunity?

The strongest opportunity is a differentiated generic or authorized-generic product with operational advantages:

• Dye-free, sugar-free, alcohol-free oral solution.
• Low-volume dosing with an oral syringe.
• Improved taste without delayed release.
• Child-resistant and unit-dose packaging.
• Multiple tablet strengths with clear visual differentiation.
• Stable supply of codeine phosphate and acetaminophen.
• Formulation documentation supporting ANDA approval.
• Patent claims directed to a measurable technical result.

A premium price is difficult to sustain for a conventional acetaminophen/codeine tablet. Pricing power is more plausible where the product reduces dispensing errors, improves adherence, solves a formulation problem, or supports institutional opioid stewardship.

Key Takeaways

• TYLENOL WITH CODEINE is an established acetaminophen/codeine combination with extensive generic competition.
• The main commercial opportunity is excipient-enabled differentiation, not new active-ingredient protection.
• Taste-masked, sugar-free, alcohol-free oral solutions have the clearest lifecycle-management potential.
• Abuse-deterrent excipients may create value but require substantial FDA evidence and can impair dissolution or manufacturing economics.
• Conventional tablet excipients provide limited patent strength unless linked to a demonstrable technical effect.
• Current Orange Book, patent, and Paragraph IV analysis must be performed for the specific reference-listed drug and dosage form.
• Biosimilar risk does not apply; generic substitution and controlled-substance supply risk do.
• Packaging, dosing devices, stability, and manufacturing reliability may create more practical value than a minor excipient change.

FAQs

Is TYLENOL WITH CODEINE still patent protected?

Conventional acetaminophen/codeine products have been marketed for decades and face generic competition. Current patent status must be determined by the specific FDA-listed product and formulation.

Can a new flavor of TYLENOL WITH CODEINE receive patent protection?

A flavor alone is unlikely to provide strong patent protection. A flavor system linked to improved masking, stability, dose acceptance, or another measurable technical result has a stronger patent position.

Can TYLENOL WITH CODEINE be reformulated as an abuse-deterrent product?

Yes, but the sponsor would need to address opioid-release behavior, crushing and extraction, pharmacokinetics, manufacturing controls, labeling, and FDA abuse-deterrence requirements.

Are excipients in TYLENOL WITH CODEINE subject to FDA approval?

Excipients must be suitable for the proposed route, dosage form, and use level. Novel excipients or unusual concentrations can increase regulatory development requirements.

Does TYLENOL WITH CODEINE have biosimilar competition?

No. It is a small-molecule combination drug. Its relevant competitors are generic acetaminophen/codeine products and other analgesics.

References

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

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

3. U.S. Food and Drug Administration. (2017). FDA requires labeling changes regarding safety risks of prescription opioids containing codeine or tramadol in children and breastfeeding women. FDA.

4. U.S. Drug Enforcement Administration. (n.d.). Controlled substances schedules. U.S. Department of Justice.

5. National Library of Medicine. (n.d.). DailyMed: Acetaminophen and codeine phosphate drug labels. U.S. National Library of Medicine.