List of Excipients in Branded Drug CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	ANHYDROUS CITRIC ACID
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	GLYCERIN
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	HIGH FRUCTOSE CORN SYRUP
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	METHYLPARABEN
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	POLYSORBATE 80
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	POVIDONE
Neos Therapeutics LP	CARBINOXAMINE MALEATE EXTENDED-RELEASE ORAL SUSPENSION	carbinoxamine maleate	62542-101	PROPYLPARABEN

Carbinoxamine Maleate Extended-Release Oral Suspension: Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: August 17, 2026

Carbinoxamine maleate extended-release oral suspension is a differentiated pediatric antihistamine product built around dosing convenience, swallowability, taste masking, and controlled drug release. The commercial reference product is KARBINAL ER, marketed by Tris Pharma as a prescription 4 mg/5 mL oral suspension for allergic rhinitis in patients aged 2 years and older. Its formulation strategy creates barriers beyond the active ingredient, but those barriers are more relevant to suspension performance, bioequivalence, and manufacturing control than to biological-product exclusivity.

The strongest opportunities are generic or 505(b)(2) development, pediatric allergy line extensions, alternate-flavor products, contract manufacturing, and excipient-enabled reformulation. The primary risks are relatively limited market size, competition from inexpensive second-generation antihistamines, the technical burden of proving extended-release performance, and the need to maintain dose uniformity throughout the bottle.

What is carbinoxamine maleate extended-release oral suspension?

Carbinoxamine maleate is a first-generation H1 antihistamine. The extended-release product delivers 4 mg of carbinoxamine maleate per 5 mL and is administered every 12 hours. KARBINAL ER is indicated for symptoms associated with seasonal and perennial allergic rhinitis in adults and pediatric patients 2 years and older.[1]

The dosage form is important because carbinoxamine is used in young children and patients who have difficulty swallowing tablets. The product combines:

• A liquid vehicle
• Suspended drug particles
• A viscosity-building system
• Taste and mouthfeel modifiers
• A preservative system
• pH and buffer components
• An extended-release mechanism

The product is not an immediate-release syrup. Its commercial differentiation depends on maintaining a reproducible release profile after the suspension is shaken, measured, and swallowed.

What excipients are used in carbinoxamine maleate extended-release oral suspension?

The KARBINAL ER labeling identifies a conventional but technically demanding excipient platform. The formulation includes excipients associated with suspension stability, preservation, taste, and pH control.[1]

Excipient category	Representative components in the reference product	Primary formulation function
Suspending and viscosity system	Microcrystalline cellulose and carboxymethylcellulose sodium	Limits settling, improves redispersibility, supports dose uniformity
Wetting and dispersion aid	Polysorbate 80	Promotes wetting and uniform distribution of drug particles
Humectant and mouthfeel modifier	Glycerin	Improves mouthfeel and contributes to vehicle structure
Solvent and processing aid	Propylene glycol	Supports flavor and excipient solubilization
Buffer system	Citric acid, sodium citrate	Controls pH and supports chemical stability
Preservative	Sodium benzoate	Controls microbial growth in the aqueous multidose container
Sweetener	Sucralose	Reduces bitterness and improves pediatric acceptability
Flavor system	Product-specific flavor components	Masks the bitter taste of carbinoxamine
Vehicle	Purified water	Continuous liquid phase

The exact qualitative and quantitative composition is commercially important. A competitor can use different excipients, but changes to suspending agents, preservatives, sweeteners, or flavoring can alter viscosity, sedimentation, dissolution, microbial stability, and pharmacokinetics.

Why microcrystalline cellulose and carboxymethylcellulose sodium matter

The microcrystalline cellulose-carboxymethylcellulose system is widely used in pharmaceutical suspensions because it can create a structured vehicle at relatively low concentration. The system can reduce rapid sedimentation and help the sediment redisperse after shaking.

Its concentration must be controlled tightly. Excessive viscosity can create dosing problems, poor pourability, and inaccurate delivery from oral syringes. Insufficient viscosity can cause rapid settling and concentration gradients between the top and bottom of the bottle.

A generic developer should evaluate:

1. Sedimentation volume over the labeled shelf life.
2. Redispersibility after defined standing periods.
3. Dose uniformity at the beginning, middle, and end of the bottle.
4. Syringe delivery at different angles and withdrawal speeds.
5. Rheology under refrigerated, room-temperature, and accelerated conditions.
6. Interaction between viscosity and drug-release kinetics.

How does the excipient strategy create commercial differentiation?

The formulation creates value through administration rather than through a new pharmacological mechanism. Pediatric patients often need liquid dosing, and twice-daily extended release can reduce administration frequency compared with shorter-acting formulations.

The commercial advantages include:

• Use in children unable to swallow tablets.
• Reduced dosing frequency.
• Potentially improved caregiver adherence.
• Metered delivery through an oral syringe.
• Pediatric-friendly sweetening and flavoring.
• Multidose bottle presentation without reconstitution.

The limitations are equally material. Carbinoxamine is sedating compared with many second-generation antihistamines. The FDA label warns about somnolence and contraindicates use in children younger than 2 years because of potentially fatal respiratory events associated with antihistamine use.[1] That safety profile limits broad substitution for nonsedating products such as cetirizine, loratadine, and fexofenadine.

What patents protect carbinoxamine maleate extended-release oral suspension?

The relevant intellectual-property position includes formulation and drug-delivery patents associated with Tris Pharma and the KARBINAL ER product. Public Orange Book records and patent documents should be reviewed together because the Orange Book identifies patents submitted for the approved product, while the broader patent portfolio may include claims that are not listed against the NDA.[2][3]

IP subject	Commercial relevance
Extended-release liquid suspension	Protects release behavior in an aqueous oral dosage form
Suspension vehicle and rheology	Can cover combinations of suspending agents and physical properties
Drug particle dispersion	May address uniformity and release control
Dosing regimen	May support twice-daily administration for particular patient groups
Formulation process	Can create manufacturing barriers even when composition claims are narrow
Container and dosing system	May support product-performance or administration claims

A prominent patent family associated with Tris Pharma’s extended-release liquid technology includes U.S. Patent No. 8,980,313. The patent concerns extended-release liquid formulations and is relevant to the technical platform used in products such as KARBINAL ER.[3] The exact scope of freedom to operate depends on claim construction, expiration calculations, terminal disclaimers, continuations, and the Orange Book listing applicable to the NDA.

Patent expiration cannot be determined from the product name alone. An assessment should distinguish:

• Orange Book-listed patents
• Unlisted formulation patents
• Continuation and divisional applications
• Patent-term adjustment
• Patent-term extension
• Pediatric exclusivity
• Regulatory exclusivity
• Trade-secret manufacturing controls

When does carbinoxamine maleate extended-release suspension lose exclusivity?

KARBINAL ER is a small-molecule prescription product, so biosimilar exclusivity does not apply. The relevant competitive pathways are an ANDA with a Paragraph IV certification, a 505(b)(2) application, or a non-infringing product launched after relevant patent barriers expire or are successfully challenged.

The FDA approved KARBINAL ER under NDA 203457 in 2013.[1][4] FDA approval does not itself establish a single market-exclusivity end date. The practical entry date depends on the active Orange Book patents, any regulatory exclusivity that applied at approval, and the outcome of litigation or settlement agreements.

What is the Orange Book status of KARBINAL ER?

KARBINAL ER is listed as a prescription drug product in FDA’s Orange Book under NDA 203457. The Orange Book identifies approved products, therapeutic-equivalence information, and patents submitted by the NDA holder.[2]

For commercial diligence, the relevant questions are:

• Whether the NDA remains active.
• Which patents are currently listed.
• Whether the patents cover the formulation, method of use, or both.
• Whether any patent has expired, been delisted, or been replaced by a later-listed patent.
• Whether an authorized generic has been launched.
• Whether an ANDA applicant has made a Paragraph IV certification.

The Orange Book is the controlling public source for listed patent information, but it does not reveal every trade secret, manufacturing process, or non-listed patent position.

What Paragraph IV challenges and generic entry risks exist?

A generic applicant could pursue an ANDA if it can demonstrate pharmaceutical equivalence and bioequivalence to the reference product. For an extended-release suspension, the development burden is higher than for a simple immediate-release oral solution.

A Paragraph IV strategy could target:

• Invalidity of formulation claims.
• Non-infringement based on different excipient concentrations.
• Non-infringement based on a different release-controlling mechanism.
• Obviousness of the suspension system.
• Lack of written description or enablement.
• Expiration of the relevant patent.
• Failure of the patent to claim the approved product accurately.

The generic product would need to address several technical risks:

Development issue	Risk to an ANDA applicant
Extended-release profile	Small changes in particle size or viscosity can change exposure
Suspension uniformity	Poor redispersion can produce subtherapeutic or excessive doses
Taste	A different flavor system may affect acceptability
Preservative level	Lower levels can create microbial failure; higher levels can affect tolerability
pH	Changes can affect stability, solubility, and preservative performance
Device compatibility	Oral syringes can alter delivered volume and dose accuracy
In vitro-in vivo relationship	Dissolution may not fully predict pharmacokinetic equivalence

A 505(b)(2) applicant could pursue a differentiated formulation with a new flavor, preservative, dosing device, concentration, or delivery profile. That pathway may be commercially attractive where the formulation is materially different but the company wants to rely partly on FDA’s findings for carbinoxamine.

What formulation patents protect the excipient platform?

Formulation patent risk is concentrated in the interaction among excipients rather than in any single ingredient. A claim directed only to carboxymethylcellulose, sucralose, or sodium benzoate would be relatively easy to design around. Stronger claims may recite a combination of:

• Carbinoxamine concentration
• Particle-size distribution
• Suspending-agent ratio
• Viscosity range
• pH range
• Release profile
• Sedimentation behavior
• Multidose stability
• Dosing interval

The formulation’s technical center is the balance between physical suspension stability and controlled release. A developer that replaces one excipient but reproduces the same functional combination may still face infringement arguments under composition, performance, or process claims.

Trade secrets may be as important as issued patents. These can include mixing order, hydration time for cellulose polymers, shear rate, de-aeration, drug-particle preparation, flavor incorporation, and filling conditions.

Which commercial opportunities exist for excipient innovation?

Pediatric flavor and acceptability products

The most direct opportunity is a differentiated flavor system. Strawberry, grape, cherry, and unflavored versions could address caregiver and patient preference, provided the change does not alter stability or bioequivalence.

A flavor-only 505(b)(2) product may have limited protection unless supported by improved adherence, reduced sugar, allergen avoidance, or a clinically meaningful tolerability benefit.

Sugar-free and allergen-conscious formulations

Sucralose-based products already provide a sugar-free platform. Further opportunities include:

• Reduced excipient burden.
• Colorant-free presentation.
• Alcohol-free presentation.
• Reduced propylene glycol.
• Allergen-controlled flavor systems.
• Lower sodium content.
• Pediatric oral-syringe compatibility.

These changes may support institutional formularies, specialty pharmacies, and caregiver-driven purchasing decisions.

Alternative suspension technologies

Potential technology platforms include:

• Ion-exchange resin complexes.
• Lipid or polymeric microparticles.
• Structured vehicles using alternative cellulose systems.
• In situ gelling systems.
• Nanoparticle or micronized drug dispersions.
• Powder-for-reconstitution products.
• Dual-chamber or separately preserved presentations.

Each platform must preserve a 12-hour release profile and acceptable dose uniformity. A technically novel system can support stronger patent claims but may require a more complex regulatory package.

Contract manufacturing and licensing

Tris Pharma has expertise in liquid and extended-release oral dosage forms, making platform licensing and contract development commercially relevant. Opportunities may include:

• Licensing an extended-release suspension platform to regional pharmaceutical companies.
• Supplying pediatric liquid products for generic companies.
• Developing line extensions for antihistamines and other sedating oral drugs.
• Packaging and device partnerships for oral syringes.
• Manufacturing private-label prescription pediatric liquids.

The best licensing targets are companies with established pediatric, allergy, or generic portfolios but limited liquid-formulation infrastructure.

How does carbinoxamine compare with competing antihistamines?

Product class	Typical advantage	Competitive limitation
Carbinoxamine ER suspension	Liquid dosage form and twice-daily administration	Sedation; relatively narrow market
Cetirizine oral solution	Broad pediatric use and strong generic availability	Usually once daily; less differentiated
Loratadine syrup or solution	Nonsedating profile and broad consumer recognition	Generic price competition
Fexofenadine suspension	Nonsedating profile	More complex dosing and interaction considerations
Diphenhydramine liquid	Familiar and inexpensive	Sedation and short duration
Desloratadine solution	Once-daily pediatric liquid	Strong generic competition

Carbinoxamine’s commercial position depends on patients for whom a liquid, twice-daily, first-generation antihistamine remains clinically appropriate. The product is less competitive in broad allergy markets dominated by nonsedating, once-daily alternatives.

What regulatory status and litigation issues affect the product?

The FDA approved KARBINAL ER as an NDA product. It is not a biologic, so biosimilar litigation under the Biologics Price Competition and Innovation Act is irrelevant. Any challenge would proceed through the Hatch-Waxman framework for small-molecule drugs.[4][5]

The main litigation triggers are:

• Paragraph IV certification against listed patents.
• Declaratory judgment actions.
• Patent infringement litigation after an ANDA notice.
• Citizen petitions concerning bioequivalence or product labeling.
• Patent delisting disputes.
• Settlement agreements governing generic launch timing.

A settlement could create a licensed or authorized generic launch before complete patent expiry. The economic value of such an agreement would depend on the size of the carbinoxamine market, the number of potential ANDA applicants, and the strength of the asserted claims.

What generic launch scenarios are most likely?

Scenario 1: Single first-filer challenge

A first ANDA filer could obtain 180-day exclusivity if it satisfies the statutory requirements and prevails or reaches a qualifying settlement. This would delay later generic competition and increase the value of early market entry.

Scenario 2: Non-infringing formulation

A company could develop a suspension using a different release-control system and avoid the asserted claims. This route reduces patent exposure but increases formulation and regulatory risk.

Scenario 3: 505(b)(2) differentiated liquid

A reformulated product could target improved taste, a different concentration, a new device, or an altered dosing profile. The product could obtain its own formulation patents but would likely face a higher clinical and regulatory burden than an ANDA.

Scenario 4: Authorized generic

The NDA holder or a licensee could launch an authorized generic to capture price-sensitive prescriptions and reduce the economic impact of an independent generic entrant.

How strong is the patent estate for carbinoxamine maleate extended-release suspension?

The estate is strongest where claims combine the drug, liquid dosage form, release performance, and suspension characteristics. It is weaker against simple excipient substitution if the substitute produces a materially different formulation and release mechanism.

Overall strength can be assessed as follows:

Factor	Assessment
Active ingredient protection	Weak; carbinoxamine is an old active ingredient
Dosage-form differentiation	Moderate to strong
Excipient combination protection	Moderate, depending on claim scope
Manufacturing know-how	Potentially strong and difficult to reproduce
Regulatory exclusivity	Limited relative to biologics and new chemical entities
Biosimilar protection	Not applicable
Generic substitution risk	Moderate; technical complexity delays but does not eliminate entry
Commercial moat	Narrow and dependent on pediatric liquid demand

Key Takeaways

• KARBINAL ER is the key commercial reference for carbinoxamine maleate extended-release oral suspension.
• The excipient strategy centers on suspension stability, controlled release, taste masking, preservation, and pH control.
• Microcrystalline cellulose with carboxymethylcellulose sodium is central to physical stability and dose uniformity.
• The product is a small-molecule NDA product; biosimilar competition does not apply.
• Generic entry would likely require substantial work on dissolution, rheology, redispersion, preservative efficacy, and dosing accuracy.
• The most practical commercial opportunities are ANDA development, 505(b)(2) reformulation, flavor and excipient line extensions, licensing, and contract manufacturing.
• The patent position is more valuable for the extended-release formulation and manufacturing platform than for carbinoxamine itself.
• Sedation and competition from nonsedating antihistamines constrain market expansion.

FAQs

Can carbinoxamine maleate extended-release suspension be converted into an over-the-counter product?

A switch from prescription to over-the-counter status would require FDA review of safety, labeling comprehension, self-selection, and unsupervised use. The product’s pediatric age restrictions and sedation warnings would make an OTC strategy more complex than a standard antihistamine switch.

What excipient is most important for dose uniformity?

The suspending system, particularly the microcrystalline cellulose and carboxymethylcellulose sodium combination, is central to maintaining uniform drug distribution. Polysorbate 80, particle size, mixing energy, and filling conditions also affect uniformity.

Can a generic use a different preservative from sodium benzoate?

A generic can use a different preservative if the product meets FDA requirements for pharmaceutical equivalence or the applicable 505(b)(2) standard. The change must not compromise antimicrobial protection, stability, safety, or bioequivalence.

Is a flavor change enough to obtain new patent protection?

A flavor change alone usually provides limited patent value. Stronger protection may result when the flavor change is linked to a measurable technical benefit, such as improved stability, reduced bitterness, lower excipient burden, or increased pediatric acceptability supported by appropriate evidence.

What is the main manufacturing barrier for a competing product?

The main barrier is reproducibly combining controlled release with suspension performance. The product must remain pourable, redisperse after storage, deliver an accurate dose, preserve microbial quality, and maintain the required pharmacokinetic profile through shelf life.

References

1. U.S. Food and Drug Administration. (2024). KARBINAL ER (carbinoxamine maleate) extended-release oral suspension prescribing information. Tris Pharma, Inc.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

3. United States Patent and Trademark Office. (2015). U.S. Patent No. 8,980,313, extended-release liquid formulations. U.S. Department of Commerce.

4. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database, NDA 203457. FDA.

5. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. FDA.