List of Excipients in Branded Drug KETOPROFEN

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Generic Drugs Containing KETOPROFEN

Company	Ingredient	NDC	Excipient
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	D&C YELLOW NO. 10
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	FD&C BLUE NO. 1
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	GELATIN
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	LACTOSE MONOHYDRATE
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	MAGNESIUM STEARATE
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	POVIDONE K30
Misemer Pharmaceuticals Inc	ketoprofen	0276-0504	SILICON DIOXIDE

What are the Most Frequently-Used Excipients in KETOPROFEN?

# Of NDCs	Excipient
1	AMMONIA
10	D&C RED NO. 28
7	D&C YELLOW NO. 10
1	D&C YELLOW NO. 10 ALUMINUM LAKE
1	DIBUTYL SEBACATE
1	ETHYLCELLULOSE AQUEOUS DISPERSION TYPE B
16	FD&C BLUE NO. 1

Ketoprofen Excipient Strategy, Formulation Patents, and Commercial Opportunities

Last updated: September 29, 2026

Ketoprofen is a mature nonsteroidal anti-inflammatory drug (NSAID) with limited composition-of-matter exclusivity but continuing opportunities in topical delivery, modified release, pediatric dosing, veterinary products, and regional generic markets. The strongest commercial positions are likely to come from formulation performance, tolerability, manufacturing efficiency, and differentiated delivery rather than from ketoprofen itself.

What is the commercial status of ketoprofen?

Ketoprofen is a propionic-acid NSAID used for pain, inflammation, osteoarthritis, rheumatoid arthritis, dysmenorrhea, and localized musculoskeletal conditions. It is available in oral capsules, extended-release products, topical gels, and veterinary formulations in various jurisdictions.

The principal commercial characteristics are:

Attribute	Assessment
Active ingredient	Ketoprofen
Drug class	Nonselective cyclooxygenase inhibitor
Oral dosage forms	Immediate-release capsules, tablets, and modified-release products
Topical dosage forms	Gels, creams, sprays, patches, and emulgels
Injectable use	Available in selected international and veterinary markets
US regulatory position	Mature generic category; product availability and Orange Book status are product-specific
Composition-of-matter patent risk	Generally low because ketoprofen has been marketed for decades
Formulation patent risk	Variable and potentially material for topical, modified-release, and combination products
Main safety issue	Gastrointestinal, renal, cardiovascular, hypersensitivity, and topical photosensitivity risks
Primary commercial opportunity	Differentiated delivery and improved local tolerability

Ketoprofen was approved in the United States in the 1980s, and its original prescription exclusivity has expired. FDA labeling identifies standard NSAID risks, including gastrointestinal bleeding, cardiovascular events, renal toxicity, and hypersensitivity reactions.[1]

When does ketoprofen lose exclusivity?

Ketoprofen's original regulatory and patent exclusivity has expired in major markets. The relevant commercial question is no longer when ketoprofen loses basic exclusivity, but whether a particular formulation, dosage form, method of use, or manufacturing process remains protected.

What is the Orange Book status of ketoprofen?

The FDA Orange Book lists approved drug products, patent information, and marketing status by product and sponsor. Ketoprofen products may appear as active or discontinued products depending on the specific strength, dosage form, and sponsor status.[2]

A company assessing US entry should distinguish:

1. The active ingredient, which is long generic.
2. The reference listed drug for the proposed dosage form.
3. Listed formulation or method-of-use patents.
4. Any pediatric exclusivity, orphan exclusivity, or regulatory exclusivity attached to the product.
5. Whether an ANDA applicant must submit a Paragraph IV certification.

For a conventional immediate-release ketoprofen capsule with no listed blocking patent, the main regulatory route is generally an abbreviated new drug application (ANDA). A novel delivery system may require a 505(b)(2) application rather than a conventional ANDA.

What patents protect ketoprofen products?

The remaining patent landscape is concentrated in formulation and delivery technology, not in the ketoprofen molecule.

What formulation patents may cover ketoprofen?

Potentially relevant claim categories include:

• Extended-release matrix systems
• Multiparticulate or pellet formulations
• Enteric-coated products
• Topical gels and emulgels
• Liposomal and lipid-based carriers
• Transdermal patches
• Salt or solvate forms
• Ketoprofen lysine or other salt-based compositions
• Combination products with gastroprotective agents
• Veterinary injectable and oral formulations
• Manufacturing processes that improve particle size, dissolution, or content uniformity

A generic developer should conduct a jurisdiction-specific search of the FDA Orange Book, WIPO Patentscope, Espacenet, Google Patents, and national patent registers. Patent status can differ materially between the United States, Europe, Japan, China, India, Brazil, and other markets.

How strong is the ketoprofen patent estate?

The base ketoprofen estate is weak because the active ingredient is old and widely generic. Product-specific formulation estates can be stronger when they claim a narrow release profile, a defined excipient ratio, a stable topical composition, or a delivery system supported by comparative clinical data.

Patent category	Expected strength	Commercial impact
Basic ketoprofen compound	Low	Minimal barrier
Conventional capsule	Low	Usually commodity competition
Extended-release dosage form	Medium	Can delay direct substitution
Topical hydroalcoholic gel	Low to medium	Claims may be narrow or design-around capable
Liposomal or nanoparticle system	Medium to high	Greater formulation and process complexity
Transdermal system	Medium	Requires performance and adhesion data
Manufacturing process	Low to medium	Relevant if difficult to reproduce economically
Combination with gastroprotection	Medium	May support 505(b)(2) differentiation

The practical value of a formulation patent depends on enforceable claim scope, freedom to operate, non-infringing alternatives, and whether physicians or payers recognize the delivery advantage.

What excipient strategy is appropriate for oral ketoprofen?

Oral ketoprofen has low aqueous solubility and can cause gastrointestinal irritation. Excipients should support reliable dissolution while limiting local gastric exposure and avoiding unnecessary increases in systemic absorption.

Immediate-release capsules

A standard immediate-release capsule can use:

• Microcrystalline cellulose as a diluent
• Lactose or mannitol as a secondary filler
• Croscarmellose sodium or sodium starch glycolate as a disintegrant
• Colloidal silicon dioxide as a glidant
• Magnesium stearate or sodium stearyl fumarate as a lubricant
• Hard gelatin or hydroxypropyl methylcellulose capsule shells

The formulation target is rapid, reproducible dissolution without excessive lubricant levels that could retard wetting. Particle-size control is often more important than adding large quantities of surfactant.

For poorly wettable ketoprofen, low levels of sodium lauryl sulfate or a comparable wetting agent may improve dissolution. The tradeoff is potential gastrointestinal intolerance and greater sensitivity to manufacturing variability.

Enteric-coated oral products

Enteric protection can reduce dissolution in the stomach but does not eliminate systemic NSAID risks. Candidate polymers include:

• Methacrylic acid copolymers
• Cellulose acetate phthalate
• Hydroxypropyl methylcellulose phthalate
• Polyvinyl acetate phthalate

Enteric coating creates a higher development burden because coating weight gain, acid resistance, and intestinal release must remain consistent. A product positioned around gastric protection needs clinical evidence rather than relying only on dissolution data.

Extended-release products

Extended-release ketoprofen can reduce dosing frequency, but the risk profile includes dose dumping, food effects, and prolonged exposure in patients with renal or cardiovascular risk.

Potential systems include:

• Hydrophilic hydroxypropyl methylcellulose matrices
• Insoluble polymer matrices
• Coated multiparticulates
• Osmotic systems
• Erodible lipid matrices

Hydrophilic matrices are generally the lowest-cost development route. Multiparticulate systems provide more control over release and can reduce the impact of mechanical failure in a single tablet, but they add manufacturing complexity.

What excipient strategy is appropriate for topical ketoprofen?

Topical ketoprofen offers the clearest formulation opportunity because the product can be differentiated through delivery, sensory profile, local exposure, and packaging.

Hydroalcoholic gels

A conventional ketoprofen gel may combine:

• Ethanol or isopropanol as solvent and penetration enhancer
• Propylene glycol or polyethylene glycol as cosolvent and humectant
• Carbomer or acrylate polymer as gelling agent
• Triethanolamine or another neutralizer
• Purified water
• Optional fragrance or cooling agent

These systems are inexpensive and scalable. Their weaknesses include skin drying, stinging, odor, flammability, and variable penetration across damaged or inflamed skin.

Emulgels and creams

Emulgels can improve skin feel and support sustained deposition in the skin. Typical excipient classes include:

• Medium-chain triglycerides
• Isopropyl myristate
• Glyceryl stearate
• Cetostearyl alcohol
• Polysorbates or nonionic emulsifiers
• Carbomer or cellulose-based rheology modifiers
• Propylene glycol or glycerol

An emulgel is commercially attractive where consumers prefer a lower-alcohol product. It may also support premium positioning, but the developer must control emulsion stability, preservative performance, particle size, and drug partitioning between phases.

Liposomal and lipid-based systems

Liposomal ketoprofen, nanoemulsions, nanostructured lipid carriers, and solid lipid nanoparticles can increase skin deposition and reduce the need for high ethanol concentrations. These systems may support formulation patents, but they carry higher risks involving:

• Scale-up
• Sterility or microbial control
• Physical instability
• Ostwald ripening
• Batch-to-batch particle-size variation
• In vitro to in vivo correlation
• Regulatory characterization of the carrier

The commercial case is strongest where improved local efficacy or reduced systemic exposure can be demonstrated against a conventional gel.

What safety issues affect ketoprofen excipient selection?

Topical ketoprofen has a well-established photosensitivity risk. Patients using ketoprofen gel may develop phototoxic or photoallergic reactions after exposure to sunlight or ultraviolet radiation. European regulators have issued restrictions and warnings for topical ketoprofen, including sun avoidance during treatment and for a period after use.[3]

Excipient decisions should therefore avoid unnecessary sensitizers and photoreactive components. Particular attention is required for:

• Fragrance oils
• Essential oils
• Preservatives with sensitization potential
• Alcohol concentration
• Penetration enhancers that increase systemic exposure
• Occlusive packaging that changes the dose delivered to skin

Airless pumps, metered-dose pumps, sachets, and unit-dose packages can improve dose consistency and reduce contamination. A premium topical product can use packaging as part of its differentiation without changing the active ingredient.

What generic entry risks exist for ketoprofen?

Generic entry risk is high for conventional oral ketoprofen. The main barriers are commercial rather than patent-based.

Immediate-release oral products

Likely competitive conditions include:

• Multiple generic suppliers
• Price-based tenders
• Low switching barriers
• Limited brand loyalty
• Substitution by ibuprofen, naproxen, diclofenac, and other NSAIDs

A new oral capsule needs a low-cost supply chain, reliable API sourcing, and a clear channel strategy. Manufacturing efficiency matters more than incremental excipient innovation.

Topical products

Topical competition is more fragmented. Entry risks include:

• Existing local brands
• OTC or pharmacy substitution
• Different national rules for prescription and nonprescription status
• Product-specific clinical requirements
• Consumer preference for texture and absorption
• Patent claims covering delivery systems or combinations

A developer can reduce direct price competition through a lower-irritation gel, a non-greasy emulgel, a metered-dose package, or a formulation with demonstrated skin deposition.

What is the regulatory pathway for ketoprofen reformulations?

ANDA pathway

An ANDA is most suitable for a product that matches an approved reference product in active ingredient, dosage form, strength, route, and relevant performance characteristics. Conventional ketoprofen capsules are the strongest candidates.

505(b)(2) pathway

A 505(b)(2) application may be appropriate for:

• A new topical delivery system
• A new dosage form
• A new route of administration
• A novel extended-release profile
• A combination product
• A product relying partly on published or listed-drug data

The 505(b)(2) route can provide regulatory exclusivity for certain approved changes, but it does not create broad protection for ketoprofen itself.

European and international pathways

In the European Union, generic and hybrid applications may be used depending on the product and formulation differences. Topical products with materially different excipients, absorption, or clinical claims may require additional comparative evidence. National requirements remain important because ketoprofen topical products have different prescription and warning regimes across markets.[4]

Which companies are challenging ketoprofen exclusivity?

Ketoprofen is a mature generic molecule, so competition is distributed across generic manufacturers rather than concentrated in a single high-profile Paragraph IV dispute. Potential competitors include regional generic companies, contract manufacturers, branded topical developers, and veterinary pharmaceutical companies.

Current Paragraph IV activity must be assessed against the specific FDA-listed product and patent at the time of filing. There is no single ketoprofen patent challenge that defines the market in the way seen with newer high-value medicines.

What licensing deals and partnerships are commercially relevant?

Licensing opportunities are more likely to involve technology or territory than the ketoprofen molecule. Relevant structures include:

• Regional licensing of topical brands
• Contract development and manufacturing of gels or emulgels
• Licensing of lipid or nanoparticle delivery platforms
• Veterinary distribution agreements
• In-licensing of combination products
• API supply agreements with dual-source protection
• Co-development of 505(b)(2) reformulations

A technology owner with a validated topical platform may obtain greater value from multiple regional licenses than from a single global transaction. The strongest deal assets will have comparative pharmacokinetic, skin-deposition, tolerability, or adherence data.

How does ketoprofen compare with competing NSAIDs?

Product	Main advantage	Main weakness	Commercial implication
Ketoprofen	Established efficacy; topical and oral formats	Photosensitivity for topical products; NSAID class risks	Best positioned through delivery differentiation
Ibuprofen	Broad consumer recognition; large OTC market	Heavy price competition	Difficult to displace in oral OTC channels
Naproxen	Longer duration of action	GI and cardiovascular concerns	Strong oral comparator
Diclofenac	Powerful topical franchise	Crowded market; class warnings	Major topical competitor
Dexketoprofen	Enantiomer-based positioning; rapid analgesic claims	Separate regulatory and IP analysis	Potential premium oral comparator
Ketorolac	Strong short-term analgesia	More restricted safety profile	Limited chronic-use overlap

Ketoprofen is unlikely to win a broad commodity oral market against ibuprofen or naproxen. It can compete more effectively in localized topical pain, selected veterinary indications, and markets where ketoprofen remains familiar to prescribers.

What revenue exposure and commercial scenarios exist?

Ketoprofen revenue is unlikely to support the economics of a high-cost global development program unless the product uses a differentiated delivery platform or targets a large veterinary or regional market.

Scenario	Product concept	Margin outlook	Main risk
Commodity generic	Immediate-release capsule	Low	Price erosion
Premium generic	Extended-release oral product	Medium	Clinical and release-performance burden
Topical reformulation	Low-alcohol emulgel	Medium to high	Consumer acceptance and evidence requirements
Advanced topical	Liposomal or lipid nanoparticle gel	High if differentiated	Scale-up and regulatory complexity
Veterinary product	Oral paste, injection, or topical product	Medium	Species-specific evidence
Combination product	Ketoprofen plus gastroprotective or complementary agent	Medium to high	Combination approval and patent clearance

What manufacturing and intellectual-property barriers matter?

The principal manufacturing barriers are:

• Consistent ketoprofen particle-size distribution
• API polymorph and solid-state control
• Uniform low-dose blending
• Coating reproducibility
• Topical rheology control
• Emulsion stability
• Preservation and microbial limits
• Scale-up of lipid or nanoparticle systems
• Packaging compatibility
• Cleaning validation for potent, poorly soluble API residues

A formulation patent is most defensible when it links a defined composition to a measurable performance benefit. Broad claims directed only to ordinary solvents, polymers, or generic topical excipients are more vulnerable to invalidity and design-around strategies.

Key Takeaways

• Ketoprofen's basic molecule is long off-patent, making conventional oral products highly exposed to generic price competition.
• The most attractive formulation opportunities are topical emulgels, low-irritation gels, extended-release systems, and advanced lipid-based delivery.
• Topical phototoxicity is a central regulatory and commercial issue.
• Excipient selection should prioritize skin tolerability, controlled penetration, physical stability, and preservative performance.
• A conventional capsule generally fits an ANDA strategy; a materially differentiated delivery system may require a 505(b)(2) or hybrid application.
• Formulation and process patents can remain commercially useful, but their value depends on narrow claim scope and comparative product data.
• Veterinary and regional international markets may offer better margins than commodity US oral generics.
• Packaging, sensory attributes, and dose consistency can support commercial differentiation without changing the active ingredient.

FAQs

Is ketoprofen still patented?

The basic ketoprofen compound is generally no longer protected by meaningful composition-of-matter exclusivity. Product-specific formulation, delivery, process, or combination patents may still exist in individual jurisdictions.

Can ketoprofen be reformulated as an OTC product?

Potentially, but the pathway depends on the jurisdiction, dosage form, strength, indication, and existing monograph or reference product. Topical products may face additional safety requirements because of photosensitivity.

Which excipient is best for improving ketoprofen topical penetration?

No single excipient is universally optimal. Ethanol, propylene glycol, isopropyl myristate, and lipid carriers can improve penetration, but the choice must balance skin irritation, systemic exposure, stability, and product feel.

Is dexketoprofen a stronger commercial opportunity than ketoprofen?

Dexketoprofen may support differentiated positioning based on enantiomer selection and dosing claims, but it requires a separate patent, regulatory, clinical, and market analysis. It is not automatically a superior commercial asset.

What is the best ketoprofen product opportunity for a generic manufacturer?

A low-cost immediate-release capsule is the easiest entry but has limited margin potential. A stable, low-irritation topical emulgel with strong packaging and sensory performance offers greater differentiation and potentially better commercial economics.

References

1. U.S. Food and Drug Administration. (2015). Medication guide: Nonsteroidal anti-inflammatory drugs (NSAIDs). FDA.

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

3. European Medicines Agency. (2011). CMDh agrees to strengthen warnings for topical ketoprofen. EMA.

4. European Medicines Agency. (2018). Guideline on the quality requirements for topical products. EMA.

5. U.S. Food and Drug Administration. (2022). Guidance for industry: Applications covered by section 505(b)(2). FDA.

6. World Health Organization. (2021). WHO guideline on the regulatory assessment of medicinal products for use in self-medication. WHO.