List of Excipients in Branded Drug COCAINE HYDROCHLORIDE NASAL

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Lannett Company Inc	COCAINE HYDROCHLORIDE NASAL	cocaine hydrochloride nasal	0527-1971	CITRIC ACID MONOHYDRATE	2037-02-07
Lannett Company Inc	COCAINE HYDROCHLORIDE NASAL	cocaine hydrochloride nasal	0527-1971	D&C YELLOW NO. 10	2037-02-07
Lannett Company Inc	COCAINE HYDROCHLORIDE NASAL	cocaine hydrochloride nasal	0527-1971	FD&C GREEN NO. 3	2037-02-07

Cocaine Hydrochloride Nasal Excipient Strategy and Commercial Opportunities

Last updated: September 24, 2026

Cocaine hydrochloride nasal solution is a regulated, hospital-administered local anesthetic and vasoconstrictor. The principal U.S. product, Numbrino, is an FDA-approved 4% and 10% nasal solution supplied in single-dose containers. Its commercial value depends less on novel excipients than on controlled-substance compliance, dose accuracy, sterile packaging, procurement access, and differentiated delivery systems. The core opportunity is a safer, more convenient nasal-procedure platform rather than a conventional retail generic.

What is cocaine hydrochloride nasal solution?

Cocaine hydrochloride nasal solution is a topical local anesthetic and vasoconstrictor used in adults for the induction of local anesthesia of the mucous membranes during diagnostic procedures and surgery involving the nasal cavities [1].

Product attribute	Numbrino information
Active ingredient	Cocaine hydrochloride
Dosage form	Nasal solution
Strengths	4% and 10%
Route	Intranasal
FDA approval	December 14, 2017
Application	NDA 209963
Controlled-substance status	Schedule II
Primary setting	Hospital, ambulatory surgery center, and specialist office
Administration	Nasal pledgets or applicator-based topical administration
Patient population	Adults
Commercial category	Prescription controlled substance

The product is not intended for routine self-administration. Administration is performed by healthcare professionals using a controlled dose before or during nasal procedures.

What excipients are used in cocaine hydrochloride nasal solution?

The Numbrino formulation uses a short excipient list consisting principally of sodium chloride, hydrochloric acid, and water for injection. The product is supplied as an aqueous solution of cocaine hydrochloride [1].

Excipient or formulation component	Primary function	Commercial relevance
Water for injection	Sterile aqueous vehicle	Supports parenteral-grade manufacturing and microbial control
Sodium chloride	Tonicity adjustment	Reduces discomfort and supports mucosal tolerability
Hydrochloric acid	pH adjustment	Supports cocaine hydrochloride solubility and product stability
Cocaine hydrochloride	Active pharmaceutical ingredient	Provides local anesthesia and vasoconstriction

The formulation does not rely on preservatives, penetration enhancers, surfactants, mucoadhesive polymers, or complex lipid systems. That simplicity limits formulation-development cost but also reduces the number of obvious excipient-based differentiation opportunities.

Why is pH control important?

Cocaine is administered as the hydrochloride salt. An acidic aqueous environment supports salt-form solubility and helps maintain a reproducible solution during storage. Excessively acidic or alkaline formulations can increase nasal irritation, alter comfort, and affect chemical stability.

A reformulator would need to balance:

• cocaine hydrochloride solubility;
• pH-related mucosal irritation;
• chemical stability;
• compatibility with the primary container;
• dose uniformity;
• sterilization and microbial-control requirements.

Hydrochloric acid is not merely a processing aid. Its concentration and final pH can affect the product's physical and clinical performance.

Is sodium chloride necessary?

Sodium chloride is used to adjust tonicity. A hypotonic or hypertonic nasal solution may increase burning, tearing, sneezing, or local discomfort. A reformulated product could investigate alternative tonicity agents, but replacement would require comparative stability and tolerability data.

Potential alternatives include dextrose, glycerol, or other pharmaceutically accepted tonicity agents. The commercial case for replacing sodium chloride is weak unless the change improves comfort, stability, container compatibility, or shelf life.

What excipient strategies could improve the product?

The strongest excipient opportunities involve administration efficiency, mucosal retention, and packaging compatibility. Each strategy would create regulatory and development requirements because the product contains a Schedule II controlled substance.

Mucoadhesive formulations

Mucoadhesive polymers such as hydroxypropyl methylcellulose, carbomers, or certain cellulose derivatives could increase residence time on the nasal mucosa. Potential benefits include:

• less runoff into the pharynx;
• improved contact with the surgical field;
• reduced need for reapplication;
• lower total administered volume.

The main risks are increased viscosity, altered dose recovery from pledgets, delayed drug release, nasal irritation, and inconsistent distribution across the nasal cavity. A mucoadhesive cocaine formulation would require evidence that the polymer does not materially increase systemic exposure or prolong vasoconstriction beyond the intended procedure.

Low-volume concentrated solutions

A higher-concentration product could reduce fluid burden and improve application to a localized treatment area. Numbrino already has 4% and 10% strengths, so the commercial opportunity is limited unless a new concentration materially improves dosing precision or reduces waste.

The principal safety constraint is the narrow margin between the intended topical dose and excessive systemic exposure. The FDA label warns about cardiovascular and central nervous system risks associated with cocaine administration [1]. A concentrated formulation would require robust controls against dosing errors.

Spray or metered-dose delivery

A metered nasal spray could improve dose reproducibility compared with manually soaked pledgets. It could also reduce preparation time and contact between the operator and the formulation.

A spray platform would face several technical barriers:

• accurate delivery across repeated actuations;
• prevention of clogging or crystallization;
• container-closure compatibility;
• plume and droplet-size control;
• avoidance of pulmonary deposition;
• tamper resistance;
• controlled-substance inventory reconciliation.

A spray format may be commercially attractive in specialist offices, but it would likely require a new device, human-factors work, and comparative clinical evidence.

Gel and thermoresponsive systems

A nasal gel could improve retention and reduce runoff. Thermoresponsive polymers could remain fluid during administration and thicken at nasal temperature. These systems may be suitable for targeted nasal surgery but carry formulation risks involving viscosity, drug release, and removal after the procedure.

A gel is more likely to qualify as a differentiated 505(b)(2) product than a simple excipient substitution. The development program would need to demonstrate that the new vehicle does not change systemic exposure, local toxicity, onset, duration, or procedural effectiveness.

Preservative-free unit-dose packaging

Preservative-free single-dose packaging is commercially attractive because it avoids repeated-use contamination concerns and reduces exposure to potentially irritating preservatives. It also supports hospital medication-safety protocols.

Unit-dose packaging can be differentiated through:

• ready-to-use ampules;
• prefilled applicators;
• labeled procedure-specific kits;
• tamper-evident packaging;
• bar-coded controlled-substance tracking;
• integrated waste documentation.

For this product class, packaging may create more practical value than a new excipient.

What FDA regulatory pathway applies to a reformulated product?

A materially different cocaine hydrochloride nasal formulation would likely be developed through a 505(b)(2) pathway if the sponsor relies in part on FDA findings for an approved cocaine hydrochloride product while presenting new formulation, device, pharmacokinetic, or clinical data [5].

Development scenario	Likely regulatory issue
Same formulation, different manufacturer	Abbreviated application and controlled-substance compliance
Same active ingredient with new excipient	Bridging, local tolerability, stability, and possible clinical studies
New spray or applicator	Device performance, human factors, dose uniformity, and combination-product review
New strength	Dose justification, exposure analysis, safety, and labeling
New indication	Clinical efficacy and safety data
New sustained-retention system	Pharmacokinetic and local-tolerance assessment
New preservative system	Nasal safety, microbiological control, and stability

Because cocaine hydrochloride is a controlled substance, FDA approval is only one part of commercialization. The sponsor must also address Drug Enforcement Administration registration, quotas, security, recordkeeping, diversion controls, and destruction procedures [3].

When did cocaine hydrochloride nasal exclusivity expire?

Numbrino received FDA approval in December 2017. New chemical entity exclusivity would not apply because cocaine hydrochloride is an established active ingredient. The product received the type of regulatory exclusivity associated with a new formulation or new clinical application rather than NCE exclusivity.

The relevant commercial timeline is:

Event	Date or status
FDA approval of Numbrino	December 14, 2017
Three-year new clinical investigation exclusivity	Generally expired in December 2020, subject to the precise FDA exclusivity record
Patent-based protection	Must be assessed against current Orange Book listings and patent records
Generic or 505(b)(2) competition	Legally possible after applicable exclusivity and patent barriers
Biosimilar pathway	Not applicable

FDA regulatory exclusivity and patent protection are separate. A product may remain commercially protected after regulatory exclusivity expires if listed patents remain enforceable.

What is the Orange Book status of cocaine hydrochloride nasal solution?

The FDA Orange Book is the controlling public source for current patent and exclusivity listings for approved drug products [2]. Cocaine hydrochloride nasal solution should be reviewed under the approved product and NDA record rather than under biologic or biosimilar databases.

The relevant patent questions are:

1. Are patents listed against the approved nasal solution?
2. Do the listed claims cover the formulation, method of use, container, or delivery system?
3. Are the patents still unexpired?
4. Has the reference sponsor submitted litigation information or a covenant not to sue?
5. Would an abbreviated applicant need to certify under Paragraph IV?

A Paragraph IV challenge could target listed patents and trigger Hatch-Waxman litigation. A successful first applicant could receive 180-day generic exclusivity if statutory requirements are satisfied. A 505(b)(2) applicant may face different certification and litigation exposure depending on the scope of its proposed labeling and the listed patents.

No biosimilar risk exists because cocaine hydrochloride is a small-molecule drug, not a biologic.

What patents protect cocaine hydrochloride nasal products?

Patent protection is likely to focus on product-specific formulation and delivery claims rather than the cocaine molecule itself. Cocaine hydrochloride is an old active ingredient, so composition-of-matter protection for the active drug is not commercially available.

Potential patent claim categories include:

• aqueous cocaine hydrochloride solutions;
• defined concentration ranges;
• pH and tonicity limits;
• single-dose containers;
• nasal applicators;
• pledget-loading systems;
• controlled or metered administration;
• methods of inducing local anesthesia during nasal procedures;
• methods that combine anesthetic and vasoconstrictive effects.

The strength of a patent estate depends on whether claims require a narrow excipient profile or a broad product characteristic. A claim limited to a specific pH range may be easier to design around than a claim covering a broad nasal solution containing cocaine hydrochloride at clinically relevant concentrations.

How strong is the patent estate for cocaine hydrochloride nasal products?

The estate is likely to be moderate rather than foundational. The active ingredient is old, and the principal product is a relatively simple aqueous formulation. The strongest defensibility would come from a combination of:

• formulation claims that are difficult to avoid without losing stability or tolerability;
• device claims tied to accurate controlled dosing;
• method-of-use claims covering the approved procedure;
• manufacturing controls that are difficult for competitors to replicate;
• regulatory and controlled-substance barriers.

Excipient-only claims are vulnerable if the same clinical result can be achieved with alternative tonicity agents, pH adjusters, or delivery formats. Device and packaging claims may provide practical differentiation but may not block all competing nasal solutions.

What generic entry risks exist?

Generic entry risk is higher for a conventional aqueous solution than for a complex nasal delivery system. The active ingredient is known, the dosage form is relatively simple, and the product is administered locally.

Generic entry scenarios

Scenario	Competitive impact
Same-strength aqueous solution	Highest direct substitution risk
Different concentration	May require separate regulatory justification
Preservative-free unit-dose product	Could compete on hospital safety and workflow
Metered spray	Could compete on dose consistency and labor reduction
Mucoadhesive gel	More differentiated, but higher development and regulatory burden
Compounded preparation	Potential price pressure, subject to applicable compounding rules
Non-cocaine local anesthetic	Therapeutic substitution rather than generic substitution

Hospital buyers may favor products that reduce waste, preparation time, and controlled-substance reconciliation work even when the acquisition price is higher.

What commercial opportunities exist for excipient suppliers?

The most attractive excipient opportunities are tied to differentiated delivery rather than basic commodity ingredients.

High-potential opportunities

1. Mucoadhesive polymers
   Suppliers could support a low-volume nasal formulation with longer mucosal residence and less runoff.

2. Low-irritation tonicity systems
   A formulation that improves patient comfort without compromising stability could support premium positioning.

3. Preservative-free sterile packaging
   Unit-dose ampules, blow-fill-seal containers, and prefilled applicators could improve workflow and reduce contamination risk.

4. Controlled-dose spray devices
   Metered delivery could reduce dose variability and improve controlled-substance accountability.

5. Procedure-specific kits
   A kit containing the drug, applicator, labeling, and disposal components could generate value through operational efficiency.

6. Container-closure systems
   Low-adsorption materials and compatible elastomers can help preserve potency and reduce extractables and leachables concerns.

Commodity sodium chloride, hydrochloric acid, and water for injection are unlikely to support meaningful differentiation unless supplied with validated sterile manufacturing, reliable availability, and package-integration services.

What manufacturing and IP barriers affect market entry?

Manufacturing barriers are substantial despite the simple formulation. A sponsor must control:

• cocaine hydrochloride sourcing;
• Schedule II inventory;
• batch reconciliation;
• diversion prevention;
• sterile filling;
• assay and impurity specifications;
• container-closure integrity;
• stability;
• packaging security;
• product destruction and returns.

Cocaine hydrochloride may adsorb to certain materials or interact with packaging components. The sponsor must evaluate drug loss, extractables, leachables, and container compatibility over the full shelf life.

A new formulation may also create a combination-product profile if supplied with a dedicated applicator or metered device. That can increase development cost but may produce stronger differentiation and more defensible intellectual property.

Which companies are challenging cocaine hydrochloride nasal products?

The competitive field includes three groups:

• manufacturers developing an approved generic aqueous solution;
• 505(b)(2) sponsors pursuing a new concentration, device, or formulation;
• hospitals and compounding pharmacies using legally permissible alternatives.

Public market data do not show a large branded competitive field comparable with major nasal corticosteroids or decongestants. Competition is more likely to emerge through a small number of specialized generic or hospital-focused manufacturers than through broad retail distribution.

What is the revenue opportunity?

The addressable market is concentrated in otolaryngology, nasal surgery, diagnostic nasal endoscopy, and ambulatory procedures. Revenue depends on procedure volume, hospital formulary access, controlled-substance handling requirements, and the product's ability to reduce preparation or administration costs.

Standalone product revenue is not consistently disclosed in public company reporting. The commercial opportunity should therefore be modeled from:

• annual eligible nasal procedures;
• utilization per procedure;
• average selling price per unit;
• hospital and ambulatory surgery center penetration;
• generic price erosion;
• share captured through kits or device-enabled products.

A premium product has the best chance of maintaining price if it reduces waste, eliminates pharmacy preparation, improves dose accuracy, or integrates controlled-substance documentation.

How does cocaine hydrochloride nasal compare with other local anesthetics?

Attribute	Cocaine hydrochloride nasal	Lidocaine nasal or topical	Oxymetazoline or phenylephrine
Local anesthetic effect	Yes	Yes	No
Vasoconstriction	Yes	Limited or absent	Yes
Controlled substance	Schedule II	Generally not Schedule II	Generally not Schedule II
Diversion controls	High	Lower	Lower
Commercial advantage	Combined anesthesia and vasoconstriction	Lower regulatory burden	Vasoconstriction without anesthesia
Main weakness	Safety, compliance, and cost	May require separate vasoconstrictor	Does not provide equivalent anesthesia

Cocaine hydrochloride's clinical value is the combination of local anesthesia and vasoconstriction in one product. Its commercial disadvantages are controlled-substance handling, cardiovascular risk, and limited outpatient self-use.

Key Takeaways

• Cocaine hydrochloride nasal solution is a sterile, preservative-free aqueous product with a short excipient list.
• The main excipients are sodium chloride, hydrochloric acid, and water for injection.
• Excipient differentiation is more commercially credible when paired with a new applicator, spray, gel, or mucoadhesive system.
• The strongest commercial opportunities are unit-dose packaging, metered administration, procedure kits, and workflow improvements.
• The FDA approved Numbrino in December 2017 under NDA 209963.
• Three-year regulatory exclusivity generally expired in December 2020, while patent protection must be assessed through current Orange Book records.
• Biosimilar competition does not apply.
• Direct generic risk is higher for a simple aqueous solution than for a device-enabled or sustained-retention formulation.
• Schedule II controls, sterile manufacturing, container compatibility, and diversion prevention are major entry barriers.
• Basic commodity excipients are unlikely to create durable commercial differentiation without integrated packaging or delivery technology.

FAQs

Can a preservative be added to cocaine hydrochloride nasal solution?

A preservative could be technically feasible, but it would require new stability, microbiological, local-tolerance, and labeling support. Preservative-free unit-dose packaging is generally more compatible with surgical and controlled-substance use.

Can a cocaine nasal spray replace nasal pledgets?

A metered spray could replace pledgets if it delivers a reproducible dose, provides adequate mucosal coverage, and meets device, human-factors, and clinical-performance requirements. It would likely require a product-specific regulatory submission.

Is cocaine hydrochloride nasal solution eligible for biosimilar competition?

No. Cocaine hydrochloride is a small-molecule active ingredient. Potential competitors would use generic or 505(b)(2) pathways rather than the biosimilar pathway.

Can a new excipient create market exclusivity?

An excipient alone does not guarantee exclusivity. Patent protection would depend on the claimed formulation, delivery system, manufacturing process, or method of use. FDA regulatory exclusivity would depend on the nature of the new product and supporting clinical investigation.

What is the most defensible commercial reformulation?

A preservative-free, metered-dose or prefilled applicator system with validated dose accuracy, secure controlled-substance handling, and improved nasal retention is more defensible than a basic change from sodium chloride to another tonicity agent.

References

1. U.S. Food and Drug Administration. (2017). Numbrino (cocaine hydrochloride) nasal solution prescribing information.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Drug Enforcement Administration. (n.d.). Controlled substance schedules and requirements for Schedule II substances.
4. United States Pharmacopeia. (2023). United States Pharmacopeia and National Formulary.
5. U.S. Food and Drug Administration. (2023). Applications covered by section 505(b)(2).
6. U.S. Food and Drug Administration. (2016). Nasal spray and inhalation solution, suspension, and spray drug products: Chemistry, manufacturing, and controls documentation.