List of Excipients in Branded Drug COCAINE HYDROCHLORIDE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Genus Lifesciences Inc	COCAINE HYDROCHLORIDE	cocaine hydrochloride	64950-362	ANHYDROUS CITRIC ACID	2037-02-07
Genus Lifesciences Inc	COCAINE HYDROCHLORIDE	cocaine hydrochloride	64950-362	D&C YELLOW NO. 10	2037-02-07
Genus Lifesciences Inc	COCAINE HYDROCHLORIDE	cocaine hydrochloride	64950-362	FD&C GREEN NO. 3	2037-02-07
Genus Lifesciences Inc	COCAINE HYDROCHLORIDE	cocaine hydrochloride	64950-362	SODIUM BENZOATE	2037-02-07
Genus Lifesciences Inc	COCAINE HYDROCHLORIDE	cocaine hydrochloride	64950-362	WATER	2037-02-07
LXO US INC	COCAINE HYDROCHLORIDE	cocaine hydrochloride	70839-362	ANHYDROUS CITRIC ACID	2037-02-07
LXO US INC	COCAINE HYDROCHLORIDE	cocaine hydrochloride	70839-362	D&C YELLOW NO. 10	2037-02-07

Cocaine Hydrochloride Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: September 24, 2026

Cocaine hydrochloride is a differentiated local anesthetic and topical vasoconstrictor with a narrow U.S. commercial market. The main U.S. reference product is Numbrino, a sterile intranasal cocaine hydrochloride solution approved for adults undergoing diagnostic procedures and surgery involving the nasal cavities. The strongest commercial opportunities are in ready-to-use sterile delivery, hospital inventory management, unit-dose packaging, and differentiated procedural kits. The weakest opportunities are in new excipient combinations that add formulation complexity without improving stability, safety, handling, or workflow.

What is the FDA regulatory status of cocaine hydrochloride?

The FDA approved Numbrino, cocaine hydrochloride nasal solution, in 2018 under New Drug Application 211799. The product is available in 4% and 10% strengths and is indicated for the induction of local anesthesia of mucous membranes during diagnostic procedures and surgery of the nasal cavities in adults (FDA, 2018).

Regulatory attribute	Cocaine hydrochloride nasal solution
Reference product	Numbrino
Active ingredient	Cocaine hydrochloride
Dosage form	Sterile nasal solution
Strengths	4% and 10%
Route	Intranasal
Indication	Local anesthesia for adult nasal diagnostic and surgical procedures
FDA application	NDA 211799
Controlled-substance schedule	Schedule II
Primary sponsor at approval	Lannett Company
U.S. approval year	2018
NCE exclusivity	Five years, generally expiring in 2023 if granted from the approval date
Biosimilar pathway	Not applicable
Likely generic pathway	ANDA, subject to applicable Orange Book patents and exclusivity

Cocaine hydrochloride is a small molecule, so biosimilar competition is not relevant. Competition would arise through an abbreviated new drug application, a 505(b)(2) application, compounded products, or alternative local-anesthetic and vasoconstrictor products.

The controlled-substance classification materially affects manufacturing, distribution, inventory control, security, ordering, returns, and post-market compliance. A formulation strategy must therefore reduce diversion and wastage risk rather than optimize only for unit manufacturing cost.

What excipients are used in cocaine hydrochloride nasal solution?

The Numbrino prescribing information identifies cocaine hydrochloride, sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection as formulation components. Hydrochloric acid and sodium hydroxide are used for pH adjustment. The formulation is an aqueous sterile solution rather than a suspension, emulsion, gel, or dry powder (FDA, 2018).

Reference formulation profile

Formulation element	Function	Commercial relevance
Water for injection	Vehicle	Requires sterile manufacturing and container-closure control
Sodium chloride	Tonicity adjustment	Supports nasal tolerability and osmolality control
Hydrochloric acid	pH adjustment	Controls chemical stability and product performance
Sodium hydroxide	pH adjustment	Fine-tunes final pH
Cocaine hydrochloride	Active ingredient	Provides local anesthetic and vasoconstrictor activity

The label reports a pH range of approximately 3.5 to 6.5. A commercial developer should treat pH as a critical quality attribute because cocaine hydrochloride stability, nasal tolerability, preservative performance, container compatibility, and assay accuracy can all be affected by pH drift.

The simplest competitive formulation is likely to remain a preservative-free or minimally excipient-loaded aqueous solution. Introducing preservatives, surfactants, viscosity modifiers, or complex buffering systems can create new toxicology, extractables, leachables, sterilization, and nasal-irritation requirements.

What excipient strategy is commercially attractive?

The strongest strategy is a low-excipient, sterile, ready-to-use solution with a narrow pH and osmolality specification. The formulation should minimize preparation steps in the operating room and reduce the need for pharmacy compounding.

1. Preservative-free unit-dose packaging

A preservative-free presentation can be attractive for intranasal use because it avoids exposure to antimicrobial preservatives that may irritate nasal mucosa or complicate repeat-use safety assessments. Single-use packaging also reduces contamination and diversion risk.

Potential presentations include:

• Single-use glass vials
• Blow-fill-seal polymer containers
• Unit-dose nasal applicator systems
• Premeasured procedural kits
• Sterile bottles supplied with calibrated administration accessories

The primary development issue is container-closure compatibility. Cocaine hydrochloride is a potent and controlled active ingredient, so the package must limit adsorption, permeation, leakage, tampering, and residual product recovery.

2. Controlled pH and osmolality

A pH-adjusted isotonic solution is commercially preferable to a formulation that depends on a complex buffer system. A low-buffer formulation can reduce excipient burden and simplify comparability testing.

Development priorities should include:

• Assay and degradation products across the proposed pH range
• Osmolality and nasal tolerability
• Stability after opening
• Agitation and transport stress
• Compatibility with pledgets, applicators, and surgical instruments
• Product recovery from the primary container

A buffer may improve pH control, but it also increases the number of formulation variables and may affect tolerability. The commercial justification for a buffer should be demonstrated through stability or usability data.

3. Low-volume, high-concentration delivery

The 4% and 10% strengths already create a platform for dose and procedure differentiation. A higher concentration can reduce administered volume, while a lower concentration may provide a broader dosing margin for selected procedures. Any additional strength would require a clear clinical and regulatory rationale.

A high-concentration formulation can create technical risks involving:

• Crystallization during storage
• Concentration gradients
• Dose uniformity
• Local tolerability
• Residual volume in the container or applicator
• Analytical method sensitivity

The commercial value of a new concentration is strongest when it improves procedure workflow or reduces waste, not when it merely expands the product line.

4. Viscosity modification

Mucoadhesive or viscosity-enhancing excipients such as cellulose derivatives, povidone, or polyols could increase residence time. The strategy has limited appeal unless clinical or workflow data show a reduction in repeat application.

A more viscous formulation may cause:

• Uneven nasal distribution
• Applicator retention
• Increased residual drug
• More difficult cleaning and disposal
• Altered onset or duration
• Additional device compatibility work

For cocaine hydrochloride, viscosity enhancement is more likely to create regulatory burden than durable differentiation unless paired with a clearly superior delivery system.

What patents protect cocaine hydrochloride products?

The cocaine molecule and cocaine hydrochloride salt are long-established substances. The primary molecule is therefore unlikely to provide meaningful modern composition-of-matter protection. Commercial protection would more likely come from formulation, container-closure, administration device, manufacturing process, or method-of-use claims.

Patent categories with practical value

Patent category	Potential claim scope	Commercial strength
Composition of matter	Cocaine hydrochloride itself	Very weak because of age of active ingredient
Formulation	pH, osmolality, concentration, stability, excipient combination	Moderate if linked to unexpected stability or tolerability
Container-closure	Controlled-substance containment, unit-dose packaging, tamper resistance	Moderate, but design-around risk is high
Administration device	Calibrated nasal applicator or procedural delivery system	Moderate to strong if device-specific
Manufacturing	Sterile filtration, filling, impurity control, packaging process	Moderate if difficult to reproduce
Method of use	Particular nasal procedures, dosing regimen, or patient population	Narrow and potentially vulnerable
Kit claims	Drug plus applicator, pledgets, disposal, or procedural components	Commercially useful but usually design-aroundable

A formulation patent should not rely only on the presence of sodium chloride or pH adjustment. Those features are conventional. Stronger claims would require evidence of an unexpected result, such as improved stability, reduced degradation, lower nasal irritation, improved dose recovery, or substantially reduced controlled-substance waste.

What is the Orange Book and exclusivity status of Numbrino?

Numbrino is an FDA-approved prescription product subject to controlled-substance requirements. The commercial exclusivity analysis has three parts: NCE exclusivity, patent listings, and the absence or presence of competing approved products.

Regulatory exclusivity

If Numbrino received five-year NCE exclusivity from its 2018 approval, that exclusivity would have expired in 2023. NCE exclusivity prevents submission of an ANDA or 505(b)(2) application relying on the listed drug during the protected period, subject to statutory exceptions. It does not prevent all independent clinical development or all forms of competition.

Orange Book patents

The commercial importance of any Orange Book-listed patent depends on:

• Patent expiration date
• Listed claims
• Whether the patent covers the drug, formulation, method of use, or device
• Whether a generic applicant can omit the patented indication
• Whether a Paragraph IV certification is filed
• Whether the NDA holder brings litigation within 45 days

For a product with an old active ingredient and a relatively simple aqueous formulation, formulation and method-of-use patents are more likely than foundational active-ingredient patents. A generic could seek a non-infringing formulation or carve out a patented indication, depending on the listed claims and FDA labeling requirements.

When does cocaine hydrochloride lose exclusivity?

The key regulatory exclusivity date was approximately five years after the 2018 approval if NCE exclusivity was granted, placing the end of that period in 2023. Patent expiry depends on the specific patents listed for the reference product and cannot be inferred from the active ingredient’s age alone.

The practical loss-of-exclusivity sequence is:

Event	Commercial effect
2018 approval	Starts regulatory exclusivity and patent-term analysis
2023 expiration of potential NCE exclusivity	ANDA and 505(b)(2) filings become more viable
Patent expiration or successful Paragraph IV challenge	Removes listed patent barriers
First generic approval	Creates price and contracting pressure
Multiple generic approvals	Accelerates erosion and hospital substitution

Because the market is specialized and controlled, a generic may not launch immediately after eligibility. Manufacturing authorization, DEA controls, sterile-filling capacity, hospital contracting, and limited annual demand can reduce the commercial incentive.

Which companies are challenging cocaine hydrochloride exclusivity?

No major public Paragraph IV litigation profile has become a defining feature of the cocaine hydrochloride market. The competitive threat is more likely to arise from future ANDA applicants, 505(b)(2) developers, compounded preparations, and alternative anesthetic products than from an established biosimilar-style challenger.

Potential entrants would need to address:

• Schedule II registration and quota management
• Sterile manufacturing
• Controlled-substance security
• Bioequivalence or clinical bridging
• Nasal tolerability
• Drug-release and dose-delivery comparability
• Hospital procurement requirements
• Limited market size

The absence of visible litigation does not eliminate generic risk. A generic company may choose a narrow commercial launch, avoid contested indications, or wait until the patent estate weakens.

What generic launch risks exist?

Generic entry could occur through several models.

ANDA launch

An ANDA applicant would generally seek to demonstrate pharmaceutical equivalence and bioequivalence to the reference product. A nasal solution may be simpler than a complex nasal suspension or device-dependent formulation, but the applicant still must address container closure, dose delivery, sterility, and comparative product performance.

505(b)(2) launch

A 505(b)(2) applicant could pursue a modified formulation, strength, device, or indication while relying partly on existing FDA findings. This pathway may support:

• A new unit-dose package
• A new applicator
• A different concentration
• A revised procedure-specific indication
• A modified stability profile
• A combination procedural kit

The pathway may offer more differentiation than a conventional ANDA but would require additional regulatory and clinical justification.

Compounding competition

Compounding pharmacies may supply cocaine hydrochloride preparations under applicable federal and state requirements. Compounded products can compete on price or availability but generally lack the same commercial standardization, labeling, validated packaging, and national distribution profile as an FDA-approved product.

What commercial opportunities exist beyond the current nasal solution?

The most credible opportunities are workflow and packaging products rather than new pharmacology.

Hospital-ready procedural kits

A kit could combine the cocaine hydrochloride solution with sterile applicators, pledgets, dosing instructions, disposal materials, and controlled-substance accountability documentation. The drug-device combination could reduce setup time and product waste.

Unit-dose controlled-substance systems

A sealed, traceable unit-dose format could support pharmacy and operating-room controls. Differentiation may include tamper evidence, serialized packaging, residual-volume reduction, and clearer chain-of-custody documentation.

Contract manufacturing and private-label supply

The market may support specialized contract manufacturing for hospitals, ambulatory surgery centers, and regional distributors. The major barriers are DEA compliance, sterile filling, quality systems, and controlled-substance inventory management.

Geographic expansion

U.S. commercialization is the clearest opportunity because of the existing FDA precedent. International expansion is more complex because cocaine is controlled under national narcotics laws and may have limited therapeutic acceptance. A country-specific strategy would require narcotics import permissions, local pharmacovigilance, hospital demand validation, and a regulatory pathway for sterile nasal products.

How strong is the patent estate for cocaine hydrochloride?

The patent estate is likely moderate at the product-platform level but weak at the active-ingredient level.

Stronger protection

• Proprietary unit-dose packaging
• Integrated applicator systems
• Validated controlled-substance containment
• Narrow stability improvements
• Device-specific dosing or delivery
• Manufacturing processes that materially reduce impurities or waste

Weaker protection

• Cocaine hydrochloride as a known active ingredient
• Sodium chloride for tonicity
• Water for injection
• Conventional pH adjustment
• Generic nasal solution formulations
• Broad method claims covering ordinary nasal anesthesia

Commercial durability will depend more on execution, supply reliability, controlled-substance compliance, hospital contracting, and product convenience than on broad composition patents.

How does cocaine hydrochloride compare with alternative nasal anesthetics?

Product class	Local anesthesia	Vasoconstriction	Regulatory burden	Commercial position
Cocaine hydrochloride	Yes	Yes	High because Schedule II	Differentiated but narrow
Lidocaine	Yes	Usually requires separate vasoconstrictor	Lower	Broadly available
Tetracaine	Yes	Limited without combination	Moderate	Alternative local anesthetic
Oxymetazoline	No meaningful anesthesia	Yes	Lower	Vasoconstrictor alternative
Lidocaine-oxymetazoline combinations	Yes	Yes	Lower than cocaine	Direct functional competitor

Cocaine hydrochloride’s value comes from combining anesthesia and vasoconstriction in one controlled product. Its disadvantages are abuse potential, higher compliance costs, procurement restrictions, and a smaller eligible market.

What revenue exposure should investors assess?

Public revenue analysis is difficult because product sales may be reported within broader pharmaceutical segments rather than as a separately disclosed line item. The addressable market is limited by procedure volume, hospital formulary decisions, controlled-substance policies, and competition from lower-cost anesthetic combinations.

The main commercial sensitivities are:

• Number of U.S. nasal procedures using topical anesthesia
• Conversion from compounded products
• Hospital and ambulatory surgery center adoption
• Net price after group-purchasing discounts
• Generic entry timing
• DEA compliance and supply continuity
• Product wastage and residual volume
• Ability to maintain sterile manufacturing economics at low volume

A differentiated package can preserve pricing better than a reformulated solution alone. The most defensible business model is a controlled, ready-to-use procedural platform with measurable workflow benefits.

Key Takeaways

• Cocaine hydrochloride is an old small molecule with limited active-ingredient patent value.
• Numbrino established the modern U.S. regulatory reference for sterile intranasal cocaine hydrochloride solution.
• The core excipient strategy is a simple aqueous formulation using water for injection, sodium chloride, and pH adjustment.
• Preservative-free, unit-dose, tamper-evident packaging offers the clearest commercial differentiation.
• New viscosity modifiers, buffers, or complex excipient systems require strong evidence of improved performance.
• Biosimilar risk is irrelevant; ANDA and 505(b)(2) competition are the relevant pathways.
• Potential NCE exclusivity from the 2018 approval would have ended in 2023.
• Formulation, device, packaging, method-of-use, and manufacturing patents are more relevant than composition patents.
• Controlled-substance compliance, sterile manufacturing, and hospital workflow are larger barriers than excipient cost.
• The strongest opportunity is a ready-to-use nasal procedural kit with validated dosing, traceability, and low product waste.

FAQs

Is cocaine hydrochloride nasal solution preservative-free?

The Numbrino formulation is based on cocaine hydrochloride, sodium chloride, water for injection, and pH adjustment with hydrochloric acid and sodium hydroxide. The labeling does not identify a conventional antimicrobial preservative as a formulation ingredient.

Can a company patent a new cocaine hydrochloride formulation?

Yes. A new formulation may be patentable if it demonstrates novelty and non-obviousness, such as improved stability, reduced irritation, improved dose recovery, or a distinct delivery system. Conventional use of saline and pH adjustment is unlikely to support broad claims by itself.

Can compounded cocaine hydrochloride compete with Numbrino?

Compounded preparations may compete in selected settings, subject to applicable federal and state requirements. They may have advantages in flexibility or price but generally lack the same FDA-approved labeling, standardized packaging, and national commercial infrastructure.

Is cocaine hydrochloride subject to a REMS program?

The principal regulatory burden is its Schedule II controlled-substance status. Controlled-substance handling, security, ordering, inventory, dispensing, and disposal obligations apply regardless of whether a separate REMS program is required.

What is the best commercial product extension for cocaine hydrochloride?

A sterile, single-use procedural kit with a calibrated applicator, tamper-evident packaging, dose traceability, and controlled-substance waste controls is more commercially credible than a formulation with additional excipients but no demonstrated clinical or workflow benefit.

References

1. U.S. Food and Drug Administration. (2018). Numbrino (cocaine hydrochloride) nasal solution prescribing information. FDA.

2. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. FDA.

3. U.S. Food and Drug Administration. (1999). Applications covered by section 505(b)(2). FDA.

4. U.S. Food and Drug Administration. (2016). Inactive ingredient database. FDA.

5. U.S. Drug Enforcement Administration. (2023). Controlled substances schedules. U.S. Department of Justice.

6. U.S. Pharmacopeia. (2024). Cocaine hydrochloride monograph. United States Pharmacopeial Convention.