List of Excipients in Branded Drug NASALCROM

Generic Drugs Containing NASALCROM

Company	Ingredient	NDC	Excipient
Prestige Brands Holdings Inc	cromolyn sodium	52183-199	BENZALKONIUM CHLORIDE
Prestige Brands Holdings Inc	cromolyn sodium	52183-199	EDETATE DISODIUM
Prestige Brands Holdings Inc	cromolyn sodium	52183-199	WATER

What are the Most Frequently-Used Excipients in NASALCROM?

# Of NDCs	Excipient
1	BENZALKONIUM CHLORIDE
1	EDETATE DISODIUM
1	WATER

NasalCrom Excipient Strategy and Commercial Opportunities

Last updated: September 14, 2026

NasalCrom is an over-the-counter cromolyn sodium nasal spray for prevention of nasal allergy symptoms. Its commercial position is based on a low-complexity aqueous formulation, an established safety profile, and a non-sedating mechanism rather than on patent exclusivity. The largest opportunities are preservative-free delivery, improved nasal residence time, better pediatric usability, private-label supply, and device-led differentiation.

What is NasalCrom and how is it regulated?

NasalCrom contains cromolyn sodium, a mast-cell stabilizer used to prevent symptoms of allergic rhinitis. The U.S. product delivers 5.2 mg of cromolyn sodium per spray and is marketed as a nonprescription nasal spray.[1]

Attribute	NasalCrom profile
Active ingredient	Cromolyn sodium
Route	Intranasal
Dose strength	5.2 mg per spray
Dosage form	Aqueous metered nasal spray
U.S. status	Over-the-counter product
Primary use	Prevention of nasal allergy symptoms
Drug class	Mast-cell stabilizer
Prescription status	Nonprescription
Biological product status	Not applicable
Reference product	NasalCrom nasal spray

Cromolyn sodium acts locally and has limited systemic exposure. That supports an excipient strategy focused on spray performance, mucosal tolerability, microbial control, and shelf-life rather than systemic bioavailability enhancement.[1,2]

What excipients are used in the marketed NasalCrom formulation?

The U.S. label identifies the following inactive ingredients:

Excipient	Likely formulation function
Benzalkonium chloride	Antimicrobial preservative
Edetate disodium	Chelating agent; supports preservative performance and stability
Hypromellose	Viscosity modifier and mucosal residence-time aid
Sodium chloride	Tonicity adjustment
Sodium phosphate monobasic	Buffer component
Sodium phosphate dibasic	Buffer component
Purified water	Vehicle

This composition is conventional for a preserved aqueous nasal spray. Hypromellose provides modest viscosity and may reduce rapid drainage from the nasal cavity. The phosphate system controls pH, sodium chloride supports isotonicity, and edetate disodium binds trace metals that can promote degradation or weaken preservative performance.[1,3]

What excipient strategy supports a competitive cromolyn nasal spray?

A successful product should preserve the core advantages of NasalCrom while reducing known limitations of multidose nasal formulations. The principal design variables are preservative use, viscosity, pH, tonicity, spray plume, droplet-size distribution, and microbial robustness.

Should a new product use benzalkonium chloride?

Benzalkonium chloride is commercially useful because a multidose aqueous nasal spray must control microbial contamination after opening. Its disadvantages are regulatory and market-related:

• Some consumers avoid benzalkonium chloride because of concerns about chronic nasal exposure.
• Repeated exposure may create a tolerability disadvantage in patients using a product throughout an allergy season.
• A preservative-free claim can support premium positioning.
• Removing the preservative increases dependence on container-closure integrity, pump design, microbial control, and in-use stability.

A preservative-free cromolyn product is therefore a credible commercial opportunity, but it requires a different packaging strategy. Suitable approaches include unit-dose containers, multidose systems with microbial-barrier pumps, or packaging that minimizes product backflow into the reservoir.

How should hypromellose be used?

Hypromellose is one of the most commercially relevant excipients in the current formulation. Increasing concentration can improve nasal retention, but excessive viscosity may create:

• Higher actuation force
• Larger or less uniform droplets
• Poorer plume geometry
• Residual sensation in the nose
• Reduced patient acceptance
• Greater risk of pump clogging

A reformulated product should optimize viscosity against emitted dose, spray pattern, plume geometry, and deposition. A higher-viscosity formula is not inherently superior. The target is sufficient residence time without making the product feel heavy or impairing atomization.

What pH and tonicity profile is appropriate?

The product should remain near a physiologically tolerable nasal pH and should avoid excessive hypotonicity or hypertonicity. The existing phosphate buffer and sodium chloride system provide a conventional platform for this purpose.

The formulation-development program should measure:

1. Cromolyn sodium assay and degradation products.
2. pH drift during accelerated and long-term storage.
3. Osmolality.
4. Viscosity across temperature.
5. Pump delivery over the labeled number of sprays.
6. Spray pattern and plume geometry.
7. Droplet-size distribution.
8. Microbial limits and preservative effectiveness.
9. Nasal irritation in clinical or human-factors studies.

Because the dose is delivered locally, changes in excipient concentration can affect clinical performance through deposition even when the nominal drug dose remains unchanged.

What formulations are protected by NasalCrom patents?

NasalCrom does not appear to have a commercially significant, long-duration patent barrier comparable to newer branded nasal products. Cromolyn sodium is an old small-molecule active ingredient, and the principal commercial value lies in brand recognition, regulatory history, manufacturing controls, and distribution.

IP category	NasalCrom commercial relevance
Cromolyn sodium composition patents	Foundational rights are expired
Basic aqueous nasal formulation	Likely vulnerable to design-around
Method-of-use patents	Limited value for broad allergy-prevention use
Excipient combination patents	Potentially available for new formulations
Device patents	Potentially available for pump or preservative-free systems
Manufacturing patents	Potentially available for process-specific controls
Current Orange Book barrier	No major active barrier is apparent from the established product profile

The strongest new intellectual-property opportunities would involve a specific combination of excipients, a preservative-free multidose container, a defined spray-performance profile, or a manufacturing process that produces a measurable stability or delivery advantage.

Broad claims covering "cromolyn sodium in water with buffer and viscosity modifier" would face substantial prior-art risk. Narrower claims could focus on:

• A specified hypromellose range.
• A defined pH and osmolality window.
• A preservative-free multidose package.
• A pump that limits microbial ingress.
• A spray plume or droplet-size distribution.
• A formulation with improved stability after repeated actuation.
• A pediatric delivery system with reduced spray force.

When does NasalCrom lose exclusivity?

NasalCrom has already passed the period of conventional small-molecule market exclusivity. The commercial question is no longer when basic exclusivity expires. It is whether a competitor can obtain and market a compliant cromolyn sodium nasal spray at an attractive cost.

The relevant barriers are now:

• FDA regulatory pathway.
• Product-specific bioequivalence or comparative performance requirements.
• Nasal spray device reproducibility.
• Preservative effectiveness.
• Stability and microbial controls.
• OTC labeling compliance.
• Retail distribution and brand recognition.

For a generic or private-label competitor, the active ingredient is not the main barrier. The pump, container-closure system, analytical methods, and finished-product performance are more important.

What is the Orange Book status of NasalCrom?

The Orange Book is relevant to products approved under an NDA or ANDA and to patents submitted for listing. NasalCrom's commercial position should not be assessed as if it were protected by a modern patent estate. Any current Orange Book entry must be evaluated by product-specific application number, patent listing, and marketing status.

The practical conclusion is that an entrant should not assume that NasalCrom's brand status creates patent exclusion. A regulatory review should confirm:

• Whether the reference product has an active NDA listing.
• Whether any patent is listed against the relevant nasal spray presentation.
• Whether the product is marketed under an OTC monograph or an approved NDA framework.
• Whether an ANDA route is available for the intended strength and device.
• Whether a 505(b)(2) application is more appropriate for an altered formulation or delivery system.

FDA's OTC framework and the product's historical approval pathway must be distinguished. A new product cannot rely on the established label merely because cromolyn sodium is an old active ingredient. Formulation, labeling, device, and performance data remain relevant.[4,5]

Are Paragraph IV challenges likely for NasalCrom?

Paragraph IV litigation risk is likely to be limited unless an active listed patent covers the reference product. A conventional cromolyn sodium nasal spray would face greater risk from regulatory and commercial competition than from a complex patent challenge.

Potential pathways include:

Entrant strategy	Likely commercial purpose
ANDA	Conventional generic equivalent, if a suitable reference pathway exists
505(b)(2) NDA	Altered excipients, new device, preservative-free system, or new dosing presentation
OTC monograph route	Product structured within the applicable monograph requirements
Private-label supply	Retailer or pharmacy-brand version of an established formulation
Device-led product	Differentiation through pump, dose counter, or unit-dose delivery

A Paragraph IV filing would matter only if the reference application has an unexpired listed patent. For an old cromolyn product, the more material risk is a first-to-market or low-cost competitor that avoids patent litigation altogether.

What are the best excipient-led commercial opportunities?

Preservative-free NasalCrom alternative

The clearest opportunity is a preservative-free product. A unit-dose format would provide the cleanest regulatory and microbiological rationale, but it would increase packaging cost and reduce convenience. A preservative-free multidose pump would offer better consumer usability but requires strong microbial-barrier performance.

Potential positioning includes:

• "Preservative-free"
• "Gentle daily allergy prevention"
• "Suitable for frequent seasonal use"
• "No benzalkonium chloride"
• "Low-drip nasal delivery"

Claims would require appropriate substantiation and FDA-compliant labeling.

Longer-residence formulation

A modest increase in viscosity using hypromellose or another compatible polymer could reduce nasal runoff. The product should avoid a gel-like texture. The commercial advantage would be a lower-drip experience and potentially fewer repeat administrations, but any dosing claim would require clinical support.

Other mucoadhesive candidates may include cellulose derivatives or polymer systems designed for nasal retention. Each candidate introduces risks involving sprayability, cleaning, preservative compatibility, and patient sensation.

Pediatric and caregiver-oriented delivery

Children may benefit from a lower-force pump, smaller nozzle, dose counter, and reduced residual volume. A pediatric presentation could be commercially differentiated without changing the active ingredient.

The formulation should prioritize:

• Low actuation force.
• Consistent dose at the beginning and end of container life.
• Minimal post-spray drip.
• Tamper-evident packaging.
• Clear priming instructions.
• Child-resistant secondary packaging where required.

Unit-dose and travel formats

Single-use or short-use packages can support preservative-free positioning and improve portability. They may also reduce contamination concerns for intermittent users. The tradeoff is higher packaging cost, more material usage, and lower shelf efficiency.

Combination products

Combining cromolyn with an intranasal antihistamine or another allergy therapy could create a differentiated product, but this would move the program beyond a simple generic strategy. The combination would require new compatibility, safety, efficacy, labeling, and regulatory work. It also would face competition from established intranasal antihistamines and corticosteroids.

How does NasalCrom compare with competing allergy products?

Product category	Primary advantage	Excipient opportunity versus cromolyn
Intranasal corticosteroids	Strong efficacy across allergic rhinitis symptoms	Gentler positioning, nonsteroidal messaging, preservative-free delivery
Intranasal antihistamines	Rapid symptom relief	Longer-residence cromolyn spray and lower bitter-drip profile
Saline sprays	Low cost and simple formulation	Add cromolyn value while retaining tolerability
Oral antihistamines	Convenience and systemic dosing	Local action without sedating or systemic positioning
Cromolyn sodium	Established nonsteroidal prevention	Better pump, preservative-free package, improved adherence

Cromolyn is unlikely to win a direct efficacy comparison against the strongest intranasal corticosteroids for moderate or severe symptoms. Its commercial opportunity is narrower: prevention, frequent use, nonsteroidal positioning, and tolerability.

What manufacturing and geographic barriers exist?

Cromolyn sodium itself is not a major manufacturing barrier. The critical controls are finished-product and device controls:

• Accurate low-volume metering.
• Homogeneous active distribution.
• Stable buffer and preservative system.
• Low bioburden.
• Container-closure integrity.
• Pump reproducibility.
• Compatibility between formulation and plastic components.
• Extractables and leachables.
• Stability after repeated use.

In the United States, FDA OTC and NDA requirements dominate. In Europe and other markets, national or regional requirements for nasal sprays, preservatives, medical-device components, and pharmaceutical quality systems apply. A single global formulation may not be optimal because preservative expectations, pediatric labeling, and regulatory pathways differ by jurisdiction.

What revenue exposure and licensing opportunities exist?

Standalone NasalCrom revenue is not generally disclosed as a separate line item by its commercial owner. The product should therefore be valued through category economics rather than a publicly reported brand revenue figure.

Licensing opportunities include:

• Acquisition or licensing of a preservative-free nasal pump.
• Contract manufacturing of cromolyn nasal spray for private-label retailers.
• Regional commercialization rights.
• Co-development of pediatric or unit-dose presentations.
• Licensing of a mucoadhesive excipient platform.
• Device partnerships with nasal-spray pump manufacturers.

The most attractive deal structure would pair an established OTC commercial organization with a formulation or device company that has differentiated nasal-delivery technology. A reformulation alone is unlikely to command substantial licensing value unless it creates a defensible package, device, or clinical claim.

Key Takeaways

• NasalCrom is a mature OTC cromolyn sodium nasal spray with limited reliance on patent exclusivity.
• Its listed excipients are benzalkonium chloride, edetate disodium, hypromellose, sodium chloride, phosphate buffers, and purified water.
• The strongest opportunity is a preservative-free product using unit-dose or microbial-barrier multidose packaging.
• Hypromellose supports nasal residence time but must be balanced against sprayability and patient feel.
• A new patent estate would need to focus on specific excipient ranges, device systems, spray performance, or manufacturing controls.
• Paragraph IV risk is less important than regulatory execution, device reproducibility, and retail distribution.
• Biosimilar risk does not apply because cromolyn sodium is a small-molecule drug.
• Commercial differentiation should target frequent-use tolerability, pediatric usability, reduced drip, and convenient packaging.
• Standalone NasalCrom revenue is not publicly separated from broader portfolio reporting.
• The best licensing targets are preservative-free pumps, nasal-retention technologies, and private-label manufacturing platforms.

FAQs

Is benzalkonium chloride necessary in NasalCrom?

It is useful in the current multidose presentation for microbial preservation, but it is not the only possible strategy. A preservative-free product would require unit-dose packaging or a validated microbial-barrier multidose system.

Can a company launch a generic cromolyn sodium nasal spray?

Potentially, but the pathway depends on the relevant FDA reference product, application status, formulation similarity, device requirements, and any applicable listed patents. The active ingredient's age does not eliminate finished-product and nasal-device requirements.

What excipient can improve cromolyn nasal retention?

Hypromellose is already used in NasalCrom and can increase viscosity and residence time. Other polymers may be considered, but each must be evaluated for spray pattern, tolerability, preservative compatibility, and stability.

Is NasalCrom suitable for a biosimilar development strategy?

No. Cromolyn sodium is a chemically synthesized small molecule, so a biosimilar pathway is not applicable. Generic, OTC, NDA, or 505(b)(2) strategies are more relevant.

Does a preservative-free cromolyn spray have strong commercial potential?

Yes, if the product provides reliable multidose microbial control or uses practical unit-dose packaging. The opportunity is strongest among frequent users, parents, and consumers seeking nonsteroidal allergy products.

References

1. DailyMed. (n.d.). NasalCrom allergy nasal spray: Cromolyn sodium nasal solution, 5.2 mg per spray. U.S. National Library of Medicine.

2. U.S. Food and Drug Administration. (n.d.). Cromolyn sodium nasal spray prescribing and product information. FDA.

3. United States Pharmacopeia. (2024). General chapter <51>: Antimicrobial effectiveness testing. United States Pharmacopeial Convention.

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.

5. U.S. Food and Drug Administration. (2024). Nasal spray and inhalation solution, suspension, and spray drug products: Chemistry, manufacturing, and controls documentation. FDA.