List of Excipients in Branded Drug UP AND UP NAPROXEN SODIUM PM

Generic Drugs Containing UP AND UP NAPROXEN SODIUM PM

Company	Ingredient	NDC	Excipient
Target Corporation	diphenhydramine hydrochloride, naproxen sodium	11673-687	CELLULOSE, MICROCRYSTALLINE
Target Corporation	diphenhydramine hydrochloride, naproxen sodium	11673-687	CROSCARMELLOSE SODIUM
Target Corporation	diphenhydramine hydrochloride, naproxen sodium	11673-687	FD&C BLUE NO. 1 ALUMINUM LAKE

What are the Most Frequently-Used Excipients in UP AND UP NAPROXEN SODIUM PM?

# Of NDCs	Excipient
1	CELLULOSE, MICROCRYSTALLINE
1	CROSCARMELLOSE SODIUM
1	FD&C BLUE NO. 1 ALUMINUM LAKE

Up & Up Naproxen Sodium PM: Excipient Strategy and Commercial Opportunities

Last updated: August 2, 2026

Up & Up Naproxen Sodium PM is an OTC immediate-release combination product that pairs naproxen sodium, an NSAID analgesic, with diphenhydramine, a sedating antihistamine used as a nighttime sleep aid. Its commercial position depends less on active-ingredient exclusivity than on low-cost excipient sourcing, tablet performance, private-label retail economics, and compliance with OTC labeling and quality requirements.

The strongest formulation opportunities are improved swallowability, faster disintegration without compromising stability, lower tablet weight, cleaner film coating, and manufacturing flexibility across multiple suppliers. The principal commercial risk is direct substitution by national-brand and store-brand products containing the same active ingredients.

What is Up & Up Naproxen Sodium PM?

The product is a nighttime pain-relief and sleep-aid caplet. The active-ingredient profile is generally:

Component	Function	Typical labeled amount
Naproxen sodium	Analgesic and NSAID	220 mg
Diphenhydramine component	Nighttime sleep aid	Equivalent to 25 mg diphenhydramine

Naproxen sodium 220 mg is equivalent to approximately 200 mg naproxen. The product is positioned against Aleve PM and other store-brand naproxen sodium/diphenhydramine products.

The formulation is expected to be an immediate-release compressed tablet or caplet with a film coat. The commercial objective is rapid release of both actives, acceptable tablet hardness, low friability, efficient coating, and sufficient shelf stability.

FDA labeling for OTC products must comply with the Drug Facts format and active-ingredient, warning, dosing, and use requirements applicable to the product category (U.S. Food and Drug Administration [FDA], 2024a).

What excipients are likely used in the formulation?

Public retail listings do not establish a single universal excipient formula for every Up & Up package, supplier, or manufacturing lot. Store-brand OTC products can be manufactured under private-label arrangements, and inactive ingredients may change after a supplier or process transfer.

A conventional formulation would likely use the following excipient classes:

Excipient class	Likely materials	Primary purpose
Diluent	Microcrystalline cellulose, lactose, dibasic calcium phosphate	Tablet mass and compression
Binder	Povidone, pregelatinized starch, hypromellose	Granule and tablet cohesion
Disintegrant	Crospovidone, croscarmellose sodium, sodium starch glycolate	Rapid tablet breakup
Lubricant	Magnesium stearate, stearic acid	Ejection and tooling protection
Glidant	Colloidal silicon dioxide	Powder flow
Film former	Hypromellose, polyvinyl alcohol	Surface protection and appearance
Plasticizer	Polyethylene glycol, propylene glycol	Film flexibility
Opacifier or colorant	Titanium dioxide or approved colorants	Appearance and light protection
Anti-tacking agent	Talc	Coating process control

The excipient selection must account for the physical properties of naproxen sodium and diphenhydramine. Naproxen sodium can produce high-dose tablet burden because 220 mg of active is present before adding the second active and excipients. Diphenhydramine may also create taste, odor, and powder-flow challenges.

A compact, direct-compression formulation would reduce processing steps and cost. Wet granulation may provide better content uniformity and compression performance but adds water, drying, process time, and scale-up complexity.

How should the excipient strategy be optimized?

The best strategy is a robust immediate-release platform rather than a highly differentiated delivery system. Four formulation priorities have the highest commercial value.

1. Control tablet size

A large nighttime caplet can create a meaningful adherence problem. Microcrystalline cellulose, functionalized calcium phosphate, and high-efficiency binders can reduce total excipient loading while preserving hardness.

The formulation should target:

• Adequate hardness for packaging and shipping
• Low friability
• Rapid disintegration
• Acceptable swallowability
• Stable coating adhesion
• Consistent weight and content uniformity

A smaller caplet can support a premium "easy to swallow" claim if the claim is substantiated and permitted under OTC labeling rules.

2. Improve disintegration without destabilizing the actives

A crospovidone or croscarmellose-based system can accelerate liquid penetration and tablet breakup. Excessive lubricant, especially magnesium stearate, can slow wetting and dissolution. Lubrication time and concentration therefore require tight process control.

A practical development screen would compare:

1. Crospovidone-dominant formulations
2. Croscarmellose sodium-dominant formulations
3. Dual-disintegrant systems
4. Direct compression versus dry granulation

The target is rapid release under standard dissolution conditions without excessive tablet softness or capping.

3. Protect against moisture and light

A film coat can reduce handling dust, improve appearance, and provide some protection against environmental exposure. The coat should remain thin enough to avoid delaying immediate release.

A low-moisture aqueous coating or solvent-minimized coating system is generally preferable for cost and manufacturing reasons. The formulation should be evaluated under accelerated and long-term stability conditions, including:

• Assay of both active ingredients
• Related substances and degradation products
• Dissolution
• Disintegration
• Tablet hardness
• Appearance and color change
• Moisture uptake
• Packaging interaction

The product should be evaluated in the intended bottle, blister, or unit-dose packaging. Packaging can provide more reliable moisture protection than increasing coating weight.

4. Build supplier flexibility into the formulation

Private-label economics favor dual sourcing. A formulation that depends on one grade of crospovidone, one pigment supplier, or one specialized coating system creates avoidable supply risk.

The development file should establish acceptable material ranges for:

• Particle-size distribution
• Bulk density
• Moisture content
• Degree of substitution for cellulose-based disintegrants
• Viscosity grade for hypromellose
• Magnesium stearate specific surface area
• Colorant concentration

Supplier changes should be managed through comparability protocols and documented risk assessment. This creates a manufacturing advantage without requiring a new consumer-facing product.

What commercial opportunities exist for excipient innovation?

Excipient innovation can support several commercial extensions.

Opportunity	Consumer benefit	Regulatory complexity	Commercial value
Smaller caplet	Easier swallowing	Low to moderate	High
Faster disintegration	Faster tablet breakup	Moderate	Moderate
Lower tablet weight	Easier handling and packaging	Low	Moderate
Dye-free formulation	Consumer preference and allergy positioning	Low	Moderate
Sugar-free formulation	Broadens inactive-ingredient positioning	Low	Low to moderate
Unit-dose blister	Portability and dosing control	Moderate	Moderate
Two-layer tablet	Separation of actives or tailored release	High	Moderate
Liquid or softgel format	Alternative dosage form	Moderate to high	High, but costly
Modified-release formulation	Extended pain relief	High	Potentially high

The most defensible near-term opportunity is a smaller, easy-to-swallow, dye-free immediate-release caplet. It can use standard compendial excipients and remain close to the existing OTC monograph pathway.

A softgel or liquid formulation could differentiate the product but introduces higher manufacturing, packaging, stability, and cost requirements. A modified-release formulation would create more substantial regulatory and patent opportunities but would no longer be a straightforward store-brand substitute.

How does Up & Up Naproxen Sodium PM compare with Aleve PM?

The active-ingredient combination is commercially similar to Aleve PM. The main differences are likely to arise from price, packaging, tablet appearance, retail placement, and inactive ingredients rather than pharmacology.

Category	Up & Up Naproxen Sodium PM	Aleve PM
Business model	Retail private label	National brand
Active ingredients	Naproxen sodium plus diphenhydramine	Naproxen sodium plus diphenhydramine
Core dosage form	Immediate-release caplet or tablet	Immediate-release caplet
Primary advantage	Lower retail price and Target distribution	Brand recognition and consumer familiarity
Excipient opportunity	Cost reduction and swallowability	Brand consistency and product-line protection
Patent dependence	Low for the basic OTC combination	Historical brand and formulation rights may exist, but active exclusivity is limited
Substitution risk	High from other store brands and Aleve PM	High from private-label products

Retail private-label products can compete effectively when the active ingredients, strength, dosing, and consumer use case are equivalent. The retailer’s margin, shelf placement, digital search ranking, and promotional pricing can matter more than formulation differentiation.

What patents protect naproxen sodium PM products?

The basic active ingredients are mature small molecules. Naproxen sodium and diphenhydramine do not create a biosimilar issue, and the basic combination is unlikely to support meaningful current exclusivity based solely on the active ingredients.

Potential intellectual-property categories include:

• Fixed-dose combination claims
• Specific dosage-form claims
• Film-coating systems
• Taste-masking or odor-control systems
• Modified-release technologies
• Manufacturing processes
• Packaging configurations
• Method-of-use claims

For the standard immediate-release combination, formulation patents would need to provide a measurable technical distinction, such as improved dissolution, stability, reduced tablet size, or a specific manufacturing advantage. Broad claims covering ordinary use of microcrystalline cellulose, crospovidone, hypromellose, or magnesium stearate would face substantial validity and obviousness risk.

No biosimilar pathway applies because the product contains chemically synthesized small-molecule actives. Generic competition is the relevant risk.

What is the Orange Book status of Up & Up Naproxen Sodium PM?

The Orange Book is not the primary exclusivity mechanism for an OTC monograph product. A store-brand OTC product may not have the same Orange Book profile as an approved prescription NDA product, and commercial protection is generally based on brand, retail distribution, manufacturing capability, and formulation know-how rather than a long-lived regulatory exclusivity period (FDA, 2024b).

A prescription-style Paragraph IV challenge is therefore not the central competitive mechanism for a conventional OTC monograph product. A competitor can usually enter by complying with applicable OTC requirements, labeling rules, quality standards, and manufacturing controls.

If the product were instead marketed under an approved NDA or 505(b)(2) application, Orange Book-listed patents, pediatric exclusivity, three-year exclusivity, or other approval-specific rights could become relevant. That is not the normal commercial structure for a standard naproxen sodium/diphenhydramine private-label product.

When does Up & Up Naproxen Sodium PM lose exclusivity?

The product has no conventional patent-driven exclusivity period comparable to a recently approved prescription drug. Its commercial exclusivity is effectively limited by:

• Retailer control of the Up & Up brand
• Supplier and manufacturing agreements
• Trade dress and trademark rights
• Distribution access
• Product quality and cost
• Any valid formulation or process patents

The active-ingredient combination is exposed to immediate competition from other compliant manufacturers. The retailer can also switch suppliers if the alternative meets specifications and cost targets.

What generic entry risks exist?

Generic and private-label entry risk is high. Competitors can target the same consumer need with:

• Naproxen sodium/diphenhydramine caplets
• Naproxen sodium tablets marketed for pain relief combined with a separate nighttime product
• Acetaminophen/diphenhydramine combinations
• Ibuprofen/diphenhydramine combinations
• Store-brand versions of Aleve PM
• Liquid or softgel nighttime analgesic products

The main barriers are not active-ingredient patents. They are formulation transfer, dissolution matching, stability, packaging, retailer qualification, and compliant OTC labeling.

A supplier with an established OTC manufacturing platform can reproduce the basic product with limited technical risk. That places downward pressure on price and makes cost-per-dose a central commercial metric.

What FDA regulatory issues affect formulation changes?

A basic immediate-release product must comply with the applicable OTC monograph framework and Drug Facts requirements. Changes that generally warrant controlled regulatory assessment include:

• New active-ingredient strengths
• New dosage forms
• Modified release
• New routes of administration
• Changes to warnings or dosing
• New combination claims
• Material changes affecting dissolution or stability
• Excipients outside established use levels or precedent

An excipient change that does not alter the product’s active ingredients, dosage form, performance, labeling, or safety profile may be manageable through postmarket quality procedures. A new delivery system or therapeutic claim could require a different FDA pathway.

The product must also meet applicable current good manufacturing practice requirements, including process validation, laboratory controls, complaint handling, stability programs, and supplier qualification (FDA, 2024c).

What licensing deals affect this product?

The basic product does not require a technology license merely because it contains naproxen sodium and diphenhydramine. Licensing becomes commercially relevant if the sponsor adopts:

• A patented softgel platform
• A proprietary taste-masking technology
• A controlled-release system
• A specialized film-coating process
• A branded delivery technology
• A licensed manufacturing process

For a low-price private-label product, third-party technology royalties can erase the value of formulation differentiation. The preferred strategy is usually an internally controlled formulation using widely available compendial excipients.

How strong is the patent estate for the product?

The patent estate for a conventional immediate-release naproxen sodium PM caplet is likely weak to moderate.

IP category	Expected strength
Naproxen sodium composition	Weak because of maturity
Diphenhydramine composition	Weak because of maturity
Basic fixed-dose combination	Weak to moderate
Standard excipient blend	Weak
Specific manufacturing process	Moderate if process-dependent and non-obvious
Modified-release technology	Moderate to strong if clinically differentiated
Packaging and trade dress	Moderate commercial protection
Trademark and retailer brand	Strong against confusingly similar branding, not against substitute products

The strongest protection would come from a clinically or commercially meaningful delivery change that is difficult to design around. A routine alternative excipient blend would generally provide limited patent value.

Key Takeaways

• Up & Up Naproxen Sodium PM is a mature OTC combination of naproxen sodium and diphenhydramine.
• The principal opportunity is an optimized immediate-release caplet, not a heavily patented formulation.
• Excipient priorities are tablet-size reduction, rapid disintegration, moisture control, coating efficiency, and dual sourcing.
• A dye-free, smaller caplet could provide practical differentiation at modest regulatory cost.
• Generic and private-label entry risk is high because the active ingredients are mature and the product is generally outside conventional prescription exclusivity structures.
• Orange Book and Paragraph IV analysis is secondary unless the product is marketed under an NDA or 505(b)(2) pathway.
• The strongest potential IP would relate to modified release, softgels, manufacturing processes, or a technically differentiated delivery system.
• Revenue exposure is likely tied to Target’s private-label retail performance, but SKU-level sales are not publicly disclosed.

FAQs

Is Up & Up Naproxen Sodium PM the same as Aleve PM?

It is commercially comparable when both products contain naproxen sodium 220 mg and diphenhydramine at the labeled nighttime strength. Inactive ingredients, tablet design, packaging, and manufacturing source may differ.

Can a dye-free version of naproxen sodium PM be marketed without a new drug application?

A dye-free version may remain within the OTC pathway if the active ingredients, dosage form, labeling, performance, and applicable monograph conditions remain compliant. The formulation change still requires quality, stability, and regulatory review.

Which excipient is most important for faster naproxen sodium PM disintegration?

The disintegrant system is usually the main driver, but lubricant level, compression force, tablet porosity, and granulation method also have major effects.

Could a softgel version obtain stronger patent protection?

Yes. A softgel can support patents directed to fill composition, solubilization, shell composition, stability, or manufacturing. Patent strength depends on technical performance and claim scope, not merely on using a softgel dosage form.

Does naproxen sodium PM face biosimilar competition?

No. Biosimilars apply to biological products. Naproxen sodium and diphenhydramine are small-molecule active ingredients and face generic and private-label competition instead.

References

1. U.S. Food and Drug Administration. (2024a). OTC drug facts label. https://www.fda.gov/drugs/drug-information-consumers/understanding-over-counter-medicines

2. U.S. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files

3. U.S. Food and Drug Administration. (2024c). Current good manufacturing practice for finished pharmaceuticals. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211

4. U.S. Pharmacopeial Convention. (2024). United States Pharmacopeia and National Formulary. USP Convention.

5. Electronic Code of Federal Regulations. (2024). Naproxen sodium and diphenhydramine OTC regulatory provisions. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D-part-300-alphabetical-listing-of-drugs/part-338աբեր