List of Excipients in Branded Drug NUMBRINO

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Lannett Company Inc	NUMBRINO	cocaine hydrochloride nasal	0527-1961	CITRIC ACID MONOHYDRATE	2037-02-07
Lannett Company Inc	NUMBRINO	cocaine hydrochloride nasal	0527-1961	D&C YELLOW NO. 10	2037-02-07
Lannett Company Inc	NUMBRINO	cocaine hydrochloride nasal	0527-1961	FD&C GREEN NO. 3	2037-02-07
Lannett Company Inc	NUMBRINO	cocaine hydrochloride nasal	0527-1961	SODIUM BENZOATE	2037-02-07
Lannett Company Inc	NUMBRINO	cocaine hydrochloride nasal	0527-1961	WATER	2037-02-07
OMNIVIUM PHARMACEUTICALS LLC	NUMBRINO	cocaine hydrochloride nasal	81665-300	CITRIC ACID MONOHYDRATE	2037-02-07
OMNIVIUM PHARMACEUTICALS LLC	NUMBRINO	cocaine hydrochloride nasal	81665-300	D&C YELLOW NO. 10	2037-02-07

Numbrino Excipient Strategy and Commercial Opportunities

Last updated: August 9, 2026

Numbrino is cocaine hydrochloride nasal solution, approved by the FDA in 2020 for induction of local anesthesia of the mucous membranes when performing diagnostic procedures and surgeries on the nasal cavities in adults. Its commercial value depends less on active-ingredient differentiation than on controlled-substance compliance, nasal tolerability, preservative strategy, packaging, and operating-room workflow.

The strongest excipient opportunities are preservative-free unit-dose delivery, reduced nasal irritation, improved wetting and residence time, and packaging that limits diversion and dosing errors. Numbrino has no biologic biosimilar issue, but it faces substitution from topical vasoconstrictors, lidocaine-based products, compounded cocaine solutions, and procedure-specific hospital protocols.

What is Numbrino and what excipients does it contain?

Numbrino contains cocaine hydrochloride in two strengths: 4% and 10%. The labeled indication is topical anesthesia of the nasal mucosa during adult diagnostic and surgical procedures. The product is administered intranasally, generally using cottonoid pledgets or applicators rather than a metered pump.[1]

Product attribute	Numbrino specification
Active ingredient	Cocaine hydrochloride
Strengths	4% and 10%
Route	Intranasal
Dosage form	Nasal solution
FDA approval	January 2020
NDA	212154
Therapeutic role	Local anesthetic with vasoconstrictive activity
Primary setting	ENT and nasal diagnostic or surgical procedures
Controlled-substance category	Schedule II
Label-listed excipients	Benzalkonium chloride, hydrochloric acid, and water-based vehicle
Preservative strategy	Benzalkonium chloride-containing multidose formulation
Administration method	Topical application to nasal mucosa, commonly with pledgets

The labeled inactive ingredients include benzalkonium chloride and hydrochloric acid in an aqueous vehicle.[1] Hydrochloric acid is used for pH adjustment. Benzalkonium chloride provides antimicrobial preservation but creates a potential reformulation target because repeated or concentrated exposure to quaternary ammonium preservatives can cause mucosal irritation and cytotoxicity concerns.

The formulation must balance four properties:

1. Cocaine hydrochloride solubility and chemical stability.
2. Rapid anesthetic onset.
3. Adequate mucosal wetting and contact time.
4. Acceptable irritation in damaged or bleeding nasal tissue.

What excipient strategy does Numbrino use?

Numbrino uses a relatively simple aqueous formulation. That approach supports rapid drug release and limits manufacturing complexity, but it leaves several potential points of differentiation.

Preservative system

Benzalkonium chloride supports microbial control in a liquid nasal product. Its commercial advantage is established preservative performance and low formulation complexity. Its main weakness is tolerability. Nasal epithelial irritation, impaired ciliary function, and local toxicity are established concerns associated with chronic or repeated benzalkonium chloride exposure, although the procedural use of Numbrino is generally short term.[2]

A preservative-free version could have greater commercial value in hospitals with strict nasal-surgery protocols or in patients with mucosal injury, chronic rhinitis, recurrent procedures, or known sensitivity to preservatives. The main technical barrier is container closure and aseptic manufacturing. A single-use ampule or blow-fill-seal unit would reduce the need for a preservative but would increase packaging, filling, and controlled-substance reconciliation requirements.

pH adjustment

Hydrochloric acid permits pH control without introducing a complex buffer system. A low-buffer formulation can reduce excipient load and simplify compatibility testing. A stronger buffer system could improve pH consistency during storage, but it may increase nasal stinging or alter cocaine release from the formulation.

The practical development target is not maximum buffering capacity. It is a narrow pH range that preserves drug stability while limiting sensory irritation. A pH-adjusted, low-buffer formulation may be more commercially attractive than a heavily buffered product.

Vehicle selection

An aqueous vehicle provides the fastest and simplest drug release. Potential alternatives include:

• Isotonic saline-based vehicles.
• Low-osmolality aqueous vehicles.
• Polyol-containing vehicles such as glycerol or propylene glycol.
• Mucoadhesive polymer systems.
• In situ gelling systems.
• Lipid or emulsion systems, although these are less attractive for rapid procedural use.

The best commercial candidates are likely isotonic or near-isotonic aqueous systems. Polyols and polymers may increase residence time but can delay drug release, increase viscosity, complicate pledget loading, or affect the operator’s ability to assess the nasal cavity.

Mucoadhesive excipients

Mucoadhesive polymers could extend residence time and reduce runoff into the nasopharynx. Candidate classes include hydroxypropyl methylcellulose, hydroxyethylcellulose, carbomers, polycarbophil, chitosan, and selected cellulose derivatives.

These materials introduce material risks:

• Delayed anesthetic onset.
• Increased viscosity and inconsistent pledget absorption.
• Difficulty removing residual formulation.
• Potential interference with visualization or cautery.
• More complex extractables and leachables testing.
• Greater variability in local dose.

For Numbrino, mucoadhesion is more likely to support a differentiated formulation patent than to improve the existing operating-room workflow. A modest-viscosity system with rapid wetting may have better adoption prospects than a high-viscosity gel.

What formulations could be protected by new patents?

New patent value would likely come from formulation and packaging claims rather than from cocaine hydrochloride itself. The active ingredient is old, and the central composition is unlikely to provide strong composition-of-matter protection.

Preservative-free single-use solution

A patent could claim:

• Cocaine hydrochloride in a defined concentration range.
• A controlled pH range.
• A defined osmolality range.
• A sterile, preservative-free aqueous vehicle.
• A single-use container.
• Stability over a commercially meaningful shelf life.

The patentability challenge is obviousness. A preservative-free sterile nasal solution is a familiar pharmaceutical design choice. Protection would be stronger if the formulation demonstrated an unexpected stability, tolerability, or dosing advantage.

Reduced-irritation formulation

A platform could combine:

• Controlled osmolality.
• Narrow pH range.
• Low ionic strength.
• Specific buffer-free or low-buffer composition.
• Reduced benzalkonium chloride concentration or no preservative.
• Demonstrated epithelial tolerability.

The most defensible claims would link composition to measurable outcomes, such as reduced ciliotoxicity, reduced epithelial disruption, or improved recovery of mucociliary function.

Controlled-residence formulation

A low-viscosity mucoadhesive solution could support claims covering:

• Polymer concentration.
• Viscosity range.
• Wetting time.
• Retention on nasal mucosa.
• Cocaine release profile.
• Use with cottonoid pledgets or nasal applicators.

Commercial value would depend on whether the system improves procedure duration or reduces repeat application. A formulation that merely increases viscosity without reducing dosing frequency would have limited value.

Unit-dose packaging

Packaging patents could cover:

• Single-use ampules containing a controlled amount of cocaine hydrochloride.
• Tamper-evident closure systems.
• Integrated applicator or pledget-loading features.
• Dose-counting and reconciliation features.
• Child-resistant and diversion-resistant packaging.
• Unit-dose packaging compatible with operating-room dispensing.

Packaging claims may be more commercially practical than formulation claims because hospitals prioritize controlled-substance accountability. The packaging must also comply with FDA drug-container requirements and DEA handling controls.[3,4]

What is the FDA regulatory status of Numbrino?

Numbrino was approved under NDA 212154 in January 2020.[1] The product is a small-molecule prescription drug, not a biologic. Biosimilar competition is therefore irrelevant. Generic competition would proceed through an abbreviated new drug application, subject to FDA requirements for pharmaceutical equivalence, bioequivalence where applicable, labeling, manufacturing, and controlled-substance compliance.

The main regulatory considerations for an improved excipient formulation are:

Development issue	Commercial impact
Preservative-free presentation	May require stronger sterility and container-closure controls
New viscosity or polymer system	May require comparative performance and local tolerability data
New device or applicator	May create combination-product review requirements
New concentration	May require a new strength approval or supplemental filing
Different dosing method	Could alter clinical and human-factors requirements
Unit-dose controlled substance	Requires secure manufacturing, distribution, inventory, and destruction controls
New preservative	Requires local tolerability and preservative-effectiveness support

A reformulated version that retains the same active ingredient and indication could potentially be developed through a supplemental NDA, depending on the scale of the formulation and delivery changes. A materially different device, route, dosing regimen, or clinical use could require a more extensive regulatory package.

When does Numbrino lose exclusivity?

FDA approval and patent exclusivity are separate issues. Numbrino’s NDA approval date was January 2020, but the publicly cited sources do not establish a patent-protected exclusivity end date for the product. The FDA Orange Book is the controlling public source for listed patents and regulatory exclusivities associated with NDA 212154.[5]

A generic applicant could challenge listed patents through a Paragraph IV certification. If a patent is listed and the NDA holder sues within the statutory period, FDA approval may be subject to a 30-month stay, subject to statutory exceptions and litigation outcomes.[6]

The principal entry scenarios are:

1. A generic applicant files an ANDA without a Paragraph IV challenge because no relevant patent is listed.
2. A generic applicant files a Paragraph IV certification against formulation, method-of-use, or packaging patents.
3. A generic applicant uses a section viii statement to omit a patented method of use, if the labeling permits.
4. A competitor markets a compounded product where legally permitted, although compounding does not provide the same substitutability or regulatory status as an FDA-approved generic.
5. A reformulated product obtains separate protection based on preservative-free delivery, packaging, or device integration.

What patent litigation and settlement risks affect Numbrino?

The primary litigation risk is a Paragraph IV challenge against any listed patent covering the formulation, method of use, or delivery system. The active ingredient itself is unlikely to support new broad exclusivity because cocaine hydrochloride has long prior-art history.

Potential litigation issues include:

• Whether the claimed pH or osmolality range is technically meaningful.
• Whether a preservative-free formulation is obvious.
• Whether a viscosity or mucoadhesive range produces an unexpected clinical benefit.
• Whether a packaging claim is patentable over conventional unit-dose controlled-substance packaging.
• Whether the generic product is pharmaceutically equivalent.
• Whether a label carve-out adequately avoids a patented method of use.

A settlement agreement could delay generic entry, authorize an early launch, or permit entry subject to a license. The economic value of any settlement would depend heavily on hospital adoption, generic substitutability, and the feasibility of compounded alternatives. No settlement terms should be assumed without a docket-specific review.

How strong is the Numbrino patent estate?

The underlying patent estate is likely weaker than the regulatory and operational barriers surrounding the product. Cocaine hydrochloride is an established active ingredient, and the current aqueous formulation is technically straightforward.

Protection category	Relative strength	Commercial assessment
Cocaine hydrochloride composition	Low	Mature active ingredient with extensive prior art
Basic aqueous solution	Low to moderate	Vulnerable to obviousness and formulation prior art
Specific pH or osmolality	Moderate	Stronger if linked to stability or tolerability data
Preservative-free formulation	Moderate	Potential value, but obviousness risk is material
Mucoadhesive formulation	Moderate	Depends on demonstrated procedure-level benefit
Unit-dose packaging	Moderate	Can support operational differentiation
Integrated applicator	Moderate to high	Stronger if it improves dosing control and diversion prevention
Method of use	Moderate	Scope may be limited by established nasal procedures
Manufacturing process	Moderate	More valuable if it controls impurity, sterility, or yield

The most defensible commercial moat would combine formulation, packaging, and workflow claims. A single patent covering only the presence or absence of benzalkonium chloride would have limited durability unless supported by unexpected results.

What commercial opportunities exist for Numbrino excipients?

Hospital and ambulatory surgery channels

The strongest opportunity is a hospital-ready presentation that reduces preparation and disposal work. A sterile, unit-dose product with a defined applicator could reduce pharmacy compounding, improve inventory control, and lower diversion exposure.

Preservative-free ENT formulation

A preservative-free presentation could target:

• High-volume ENT centers.
• Pediatric or young-adult procedural markets, subject to labeling.
• Patients with chronic nasal disease.
• Repeated nasal procedures.
• Institutions that avoid benzalkonium chloride in mucosal products.

The product would need a compelling operational benefit because preservative-free packaging raises manufacturing and logistics costs.

Applicator and delivery-system integration

A preloaded pledget, calibrated applicator, or closed transfer system could command a premium if it improves dose consistency. The strongest value proposition is reduction of:

• Pharmacy preparation time.
• Staff handling of a Schedule II substance.
• Product waste.
• Dosing variability.
• Open-container exposure.
• Inventory reconciliation errors.

Combination procedural products

A formulation combining cocaine hydrochloride with another local anesthetic or adjunctive component would face substantial regulatory and safety scrutiny. The commercial opportunity is real but narrower because of additive cardiovascular effects, compatibility concerns, and controlled-substance risk.

International and geographic expansion

Numbrino’s commercial expansion is constrained by national controlled-substance rules. International products would face separate narcotics scheduling, import controls, labeling requirements, and local clinical practice patterns. A noncontrolled alternative formulation using a different anesthetic and vasoconstrictor could have wider geographic potential but would no longer be a Numbrino reformulation.

How does Numbrino compare with competing nasal anesthetic approaches?

Approach	Anesthetic effect	Vasoconstriction	Excipient opportunity	Commercial constraint
Numbrino	Strong local anesthetic activity	Yes	Preservative-free, unit dose, applicator	Schedule II controls
Lidocaine spray or solution	Local anesthesia	Limited unless combined	Mucoadhesion, buffered tolerable solution	More crowded competition
Tetracaine-based product	Local anesthesia	Limited	Stability and delivery systems	Safety and formulation complexity
Oxymetazoline or phenylephrine	Vasoconstriction	Strong	Preservative-free delivery	Does not replace anesthesia
Lidocaine plus vasoconstrictor	Combined local effect	Yes	Combination formulation	Safety and regulatory complexity
Compounded cocaine solution	Local anesthesia and vasoconstriction	Yes	Hospital-specific formulation	Quality, sourcing, and standardization issues

Numbrino’s differentiation is the combined local anesthetic and vasoconstrictor effect. Its weakness is cost, controlled-substance handling, and the availability of lower-risk alternatives for procedures that do not require the full pharmacologic profile.

What generic entry risks exist for Numbrino?

Generic entry risk is moderate if the product has limited listed patent protection and the formulation is viewed as a conventional aqueous solution. The strongest barriers are not necessarily patent-based. They include:

• Schedule II manufacturing controls.
• DEA quotas and security requirements.
• Specialized quality systems.
• Limited market size.
• Hospital formulary inertia.
• Need for reliable supply.
• Potentially complex comparative bioequivalence strategy for a locally acting nasal product.
• Low tolerance for controlled-substance recalls or diversion events.

A generic could enter with a conventional solution and compete primarily on price. A branded reformulation would need to prevent automatic substitution or create a clear hospital economics benefit through packaging, workflow, or tolerability.

Key Takeaways

• Numbrino is a 4% and 10% cocaine hydrochloride nasal solution approved under NDA 212154 in 2020.
• Its labeled excipient system is simple: benzalkonium chloride, hydrochloric acid, and an aqueous vehicle.
• The most credible reformulation opportunity is a sterile, preservative-free, single-use presentation.
• Mucoadhesive and low-viscosity systems could support new patents, but they require evidence of improved residence time, dosing consistency, or tolerability.
• Packaging and applicator IP may be commercially stronger than broad formulation claims.
• Biosimilar risk does not apply because Numbrino is a small-molecule drug.
• Generic risk depends on Orange Book listings, Paragraph IV activity, formulation equivalence, and the economics of Schedule II manufacturing.
• Numbrino’s commercial moat is likely to depend on controlled-substance compliance, supply reliability, hospital workflow, and differentiated delivery more than on the legacy active ingredient.
• A premium reformulation must reduce pharmacy handling, dosing variability, or mucosal irritation to justify higher cost.

FAQs About Numbrino Excipient and Commercial Strategy

Can benzalkonium chloride be removed from Numbrino?

Yes, a preservative-free version could be developed in a sterile single-use container. The principal development burden would shift from preservative effectiveness to aseptic processing, container closure, sterility assurance, and controlled-substance packaging.

Could a Numbrino generic use different excipients?

A generic applicant may use different inactive ingredients if the product remains pharmaceutically equivalent, bioequivalent where required, safe, and compliant with FDA requirements. Differences that affect local tolerability, absorption, viscosity, or dosing could increase regulatory complexity.

Would a nasal gel be commercially better than Numbrino solution?

Not necessarily. A gel could increase mucosal residence time, but excessive viscosity may delay onset, complicate pledget application, and interfere with nasal visualization. A low-viscosity mucoadhesive solution is a more practical development target.

Can excipient patents block generic cocaine nasal solution entry?

They can if valid, enforceable patents are listed or otherwise support infringement claims. The commercial effect depends on claim scope, Paragraph IV litigation, possible section viii labeling, and whether a generic can design around the formulation or packaging claims.

Is Numbrino’s controlled-substance status an advantage or disadvantage?

It is both. The Schedule II status limits competition, manufacturing capacity, and distribution flexibility, but it also increases compliance costs, quota exposure, diversion risk, and hospital handling burdens. A product that solves those workflow problems could create more value than a minor chemical excipient change.

References

1. U.S. Food and Drug Administration. (2020). Numbrino (cocaine hydrochloride) nasal solution prescribing information. FDA.

2. U.S. Food and Drug Administration. (2002). Guidance for industry: Nasal spray and inhalation solution, suspension, and spray drug products: Chemistry, manufacturing, and controls documentation. FDA.

3. U.S. Food and Drug Administration. (2016). Container closure systems for packaging human drugs and biologics: Chemistry, manufacturing, and controls documentation. FDA.

4. U.S. Drug Enforcement Administration. (2024). Controlled substances schedules and requirements. U.S. Department of Justice.

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

6. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards. FDA.