List of Excipients in Branded Drug IBUPROFEN PM

Generic Drugs Containing IBUPROFEN PM

Company	Ingredient	NDC	Excipient
Walgreen Company	diphenhydramine citrate, ibuprofen	0363-0050	CELLULOSE, MICROCRYSTALLINE
Walgreen Company	diphenhydramine citrate, ibuprofen	0363-0050	CROSCARMELLOSE SODIUM
Walgreen Company	diphenhydramine citrate, ibuprofen	0363-0050	FD&C BLUE NO. 2 ALUMINUM LAKE
Walgreen Company	diphenhydramine citrate, ibuprofen	0363-0050	FERROSOFERRIC OXIDE
Walgreen Company	diphenhydramine citrate, ibuprofen	0363-0050	GLYCERYL DIBEHENATE

What are the Most Frequently-Used Excipients in IBUPROFEN PM?

# Of NDCs	Excipient
3	ALCOHOL
5	CARNAUBA WAX
15	CELLULOSE, MICROCRYSTALLINE
16	CROSCARMELLOSE SODIUM
9	D&C RED NO. 33

Ibuprofen PM Excipient Strategy and Commercial Opportunities

Last updated: August 22, 2026

Ibuprofen PM is an OTC nighttime combination of ibuprofen and diphenhydramine, typically 200 mg ibuprofen plus 38 mg diphenhydramine citrate, equivalent to 25 mg diphenhydramine. The strongest commercial opportunities are private-label and branded-generic tablets, softgels, and differentiated packaging rather than molecule-level exclusivity. Excipient selection should prioritize rapid dissolution, dose uniformity, low moisture uptake, robust compression, and a clean inactive-ingredient profile.

What is Ibuprofen PM and how is it regulated?

Ibuprofen PM is generally an oral combination analgesic and nighttime sleep-aid product. The reference product commonly associated with the category is Advil PM, marketed by Haleon in the United States. The active ingredients are:

Component	Typical strength	Function
Ibuprofen	200 mg	Analgesic, antipyretic, anti-inflammatory
Diphenhydramine citrate	38 mg	Equivalent to 25 mg diphenhydramine; nighttime sleep aid

Ibuprofen products are regulated under the FDA’s OTC internal analgesic framework. Diphenhydramine sleep-aid products are subject to FDA OTC sleep-aid requirements, including age, warning, and labeling restrictions.[1,2]

The product is intended for adults and children aged 12 years and older, subject to the applicable label. The labeling generally limits use to nighttime dosing and warns against use with other diphenhydramine-containing products, sedatives, alcohol, or other NSAIDs.[3]

What FDA pathway applies to Ibuprofen PM?

A new product can potentially reach the U.S. market through:

1. Compliance with applicable OTC monograph conditions.
2. An abbreviated new drug application if an approved reference product and appropriate regulatory pathway are available.
3. A 505(b)(2) application if the product differs materially in formulation, dosage form, delivery system, or other clinically relevant characteristics.

A standard immediate-release tablet that matches the established active ingredients, strength, dosage form, labeling, and performance profile has the lowest regulatory risk. A novel liquid-filled capsule, modified-release product, or enhanced-solubility system can require a more complex regulatory strategy.

What excipients are used in Ibuprofen PM tablets?

The exact inactive ingredients differ by manufacturer, dosage form, and market. Common excipient classes include:

Formulation function	Candidate excipients	Commercial purpose
Diluent and compression aid	Microcrystalline cellulose, dibasic calcium phosphate, lactose, mannitol	Tablet weight, hardness, manufacturability
Binder	Povidone, copovidone, hydroxypropyl cellulose	Granule strength and content uniformity
Disintegrant	Croscarmellose sodium, crospovidone, sodium starch glycolate	Rapid tablet breakup
Glidant	Colloidal silicon dioxide	Powder flow
Lubricant	Magnesium stearate, sodium stearyl fumarate	Ejection and tooling protection
Film coating	Hypromellose, polyethylene glycol, titanium dioxide, iron oxides	Identification, swallowability, moisture protection
Opacifier or colorant	Titanium dioxide, iron oxides, approved lakes	Brand differentiation and product identification

DailyMed listings should be used to verify the inactive ingredients for a specific marketed product because formulations can change over time.[3]

Which excipients are most suitable for immediate-release tablets?

A practical immediate-release platform is a dry-granulated or direct-compression tablet containing:

• Microcrystalline cellulose for compactibility.
• Crospovidone or croscarmellose sodium for rapid disintegration.
• Colloidal silicon dioxide for flow.
• Magnesium stearate or sodium stearyl fumarate at a controlled level.
• A low-weight hypromellose film coat.

Ibuprofen has poor aqueous solubility and is commonly treated as a dissolution-sensitive active ingredient. The formulation must avoid excessive lubricant, overcompression, and hydrophobic coating effects. These factors can slow wetting and dissolution.

Crospovidone is attractive where rapid capillary uptake and low gelling behavior are desired. Croscarmellose sodium can provide strong swelling but may be more sensitive to formulation composition and compression conditions. Sodium starch glycolate is effective at low concentrations but requires control of granule density and moisture.

How should formulators manage ibuprofen’s low solubility?

Ibuprofen is a weak acid with limited water solubility in its free-acid form. The main formulation risks are slow dissolution, polymorphic or particle-size variability, sticking during compression, and inconsistent exposure after food intake.

Particle-size control

Particle-size reduction can improve dissolution but may increase:

• Electrostatic charging.
• Cohesion and poor powder flow.
• Segregation from diphenhydramine citrate.
• Sticking to punches and dies.
• Dusting and occupational handling concerns.

A controlled milled grade or narrowly specified particle-size distribution is usually more commercially practical than an aggressive micronization strategy.

Salt or pH-modifying approaches

Ibuprofen lysine, sodium ibuprofen, and other salt forms can improve apparent solubility and speed of onset. They also change the active ingredient, formulation chemistry, labeling considerations, and potentially the regulatory pathway. A salt-based Ibuprofen PM product should not be treated as a simple generic substitution for free-acid ibuprofen.

Alkaline excipients or microenvironmental pH modifiers can increase ibuprofen dissolution. The tradeoff is potential impact on taste, stability, capsule compatibility, and diphenhydramine citrate behavior. Any pH-modifying system requires comparative dissolution, assay, degradation, and extractables studies.

Solid dispersions and surfactants

Solid dispersions using polymers such as povidone or copovidone can improve wetting and maintain ibuprofen in a higher-energy state. Surfactants such as sodium lauryl sulfate or poloxamers may improve dissolution but can create manufacturability, tolerability, and regulatory-quality concerns.

These approaches have greater value in a softgel or fast-onset product than in a conventional low-cost tablet, where excipient cost and process simplicity are major commercial constraints.

What formulation platforms offer the best commercial opportunity?

Immediate-release film-coated tablets

This is the lowest-risk and highest-volume platform. It supports:

• Retail pharmacy and mass-market distribution.
• Store-brand and private-label launches.
• Standard bottle and blister packaging.
• Conventional tablet manufacturing.
• Straightforward stability programs.

The primary differentiation is cost, tablet size, appearance, packaging, and supply reliability.

Liquid-filled softgels

Softgels can improve swallowability and provide a premium consumer presentation. The principal technical challenge is accommodating ibuprofen and diphenhydramine citrate in a stable fill system.

Potential designs include:

• A suspension of micronized ibuprofen with dissolved diphenhydramine citrate.
• A dual-phase fill.
• A solubilized ibuprofen salt system.
• A two-piece capsule with separate compartments or granules.

Softgels may command a higher retail price, but they require specialized encapsulation, shell compatibility testing, oxygen and moisture control, and more demanding stability work.

Caplets and smaller tablets

A caplet can improve swallowing relative to a round tablet, but the combined dose and excipient load can produce a relatively large unit. A bilayer or multilayer tablet can separate the actives physically, but it adds manufacturing complexity without necessarily creating a strong consumer benefit.

A mini-tablet or multiparticulate capsule could address swallowability, but this platform is more suitable for a premium or differentiated product than a conventional generic.

Oral liquids

An oral liquid is commercially less attractive for adult nighttime use because ibuprofen’s poor solubility creates taste-masking, suspension stability, and dose-uniformity challenges. Diphenhydramine citrate is water soluble, but combining it with ibuprofen requires a carefully controlled suspension or solubilized system.

The opportunity is limited to consumers who cannot swallow tablets. It may have higher development cost and lower retail demand than solid oral products.

What excipient claims can support product differentiation?

Excipient strategy can support marketing differentiation, but inactive ingredients alone generally do not create durable exclusivity. Commercial claims may include:

• Dye-free.
• Sugar-free.
• Lactose-free.
• Gluten-free, subject to substantiation.
• Gelatin-free.
• Vegan or plant-based capsule shell.
• Lower tablet weight.
• No artificial flavors or preservatives.
• Alcohol-free liquid formulation.

These claims require supplier qualification, analytical substantiation, and regulatory review of labeling language. They can be valuable in e-commerce search, pharmacy substitution, and private-label line extensions.

A clean-label formulation must not compromise dissolution, physical stability, or manufacturing efficiency. For example, replacing titanium dioxide, lactose, or gelatin can affect appearance, coating opacity, capsule performance, or supply-chain cost.

What patents protect Ibuprofen PM products?

The core active ingredients, ibuprofen and diphenhydramine, are long-established compounds. The principal commercial opportunity therefore does not depend on basic composition-of-matter patent protection.

Potentially relevant IP categories include:

IP category	Typical scope	Risk level for standard products
Composition patent	Ibuprofen plus diphenhydramine combination	Generally low for longstanding products
Formulation patent	Specific excipient system, dissolution profile, or dosage form	Moderate if a branded formulation is targeted
Softgel patent	Fill composition, shell, suspension, or manufacturing process	Moderate to high for differentiated softgels
Method-of-use patent	Nighttime pain treatment or sleep-related use	Usually limited in mature OTC markets
Packaging patent	Child-resistant, unit-dose, or adherence packaging	Low to moderate
Manufacturing patent	Granulation, coating, filling, or particle engineering process	Product-specific

A company should conduct a current patent search by product, assignee, formulation, and jurisdiction before launch. The relevant claims may sit outside the basic ibuprofen or diphenhydramine compound records.

What is the Orange Book status of Ibuprofen PM?

The Orange Book does not function as a comprehensive register of every OTC branded product or every private-label combination. A listed product must be assessed by its specific FDA approval pathway and application record.[4]

For a conventional OTC Ibuprofen PM product, commercial barriers are more likely to arise from:

• FDA monograph compliance.
• Labeling and safety requirements.
• Product-specific formulation or process patents.
• Trademark and trade-dress rights.
• Manufacturing scale and quality systems.
• Retail distribution.

The absence of a meaningful Orange Book patent barrier does not eliminate formulation or process IP risk. It does, however, reduce the likelihood that a standard immediate-release entrant faces a classic small-molecule patent cliff.

When does Ibuprofen PM lose exclusivity?

Ibuprofen PM is already a mature OTC category. There is no single upcoming loss-of-exclusivity date comparable to a patented prescription drug.

Exclusivity is distributed across several assets:

1. Compound patents, which are generally expired.
2. Product-specific formulation patents, if any remain enforceable.
3. Regulatory exclusivity, which depends on the relevant FDA application and pathway.
4. Trademarks and trade dress, which can remain valuable after generic entry.
5. Manufacturing know-how and supplier relationships.

The category is therefore open to generic and private-label competition, subject to FDA requirements and any live product-specific rights.

How many patents cover Ibuprofen PM?

A reliable patent count cannot be derived from the product name alone because patent families may claim:

• The combination.
• Specific salt forms.
• Immediate-release or rapid-release dosage forms.
• Softgel fills.
• Particle-size ranges.
• Coating systems.
• Packaging.
• Manufacturing processes.
• Use with other active ingredients.

Patent counts should be family-normalized and separated by active, formulation, process, and packaging claims. Counting every publication would overstate the enforceable estate.

Are Paragraph IV challenges relevant to Ibuprofen PM?

Paragraph IV litigation is relevant only where a proposed ANDA references an approved drug application with listed patents and certifies that those patents are invalid, unenforceable, or not infringed.[5]

For a mature OTC combination, the more likely launch routes may involve monograph compliance, a product-specific application, or a 505(b)(2) strategy rather than a conventional Paragraph IV campaign. If a reference product has listed formulation or method patents, a Paragraph IV challenge could still arise.

The practical risk analysis should focus on:

• Whether the reference product has a qualifying FDA application.
• Whether patents are listed for the relevant strength and dosage form.
• Whether the proposed product uses the same formulation architecture.
• Whether the entrant can carve out protected labeling.
• Whether a non-infringing formulation can match dissolution and stability requirements.

Which companies are challenging the Ibuprofen PM market?

The competitive field includes branded OTC manufacturers, generic drug companies, store-brand suppliers, contract manufacturers, and private-label distributors. Likely competitive groups include:

• Branded analgesic companies selling nighttime pain products.
• Large generic manufacturers with OTC portfolios.
• Retailer-owned brands.
• E-commerce private-label operators.
• Softgel specialists.
• Contract development and manufacturing organizations.

Competition is driven less by patented active ingredients than by retail placement, cost of goods, packaging, quality consistency, and supply continuity.

What manufacturing and IP barriers affect entry?

The main manufacturing barriers are operational:

• Uniform blending of two actives with different particle properties.
• Ibuprofen sticking and picking during compression.
• Lubrication control.
• Rapid dissolution despite hydrophobic ibuprofen.
• Film-coat moisture protection.
• Stability of diphenhydramine under heat and humidity.
• Segregation during high-speed tablet production.
• Child-resistant packaging validation.
• Control of nitrosamines and other process-related impurities where applicable.

A high-value manufacturing strategy uses a controlled ibuprofen grade, validated blending sequence, low-shear lubrication, and dissolution testing that reflects the final commercial process rather than only laboratory-scale batches.

What revenue opportunities exist for Ibuprofen PM?

Ibuprofen PM offers four main commercial opportunities:

Opportunity	Margin potential	Development risk	Main advantage
Store-brand tablet	Low to moderate	Low	Volume and simple manufacturing
Premium film-coated caplet	Moderate	Low to moderate	Better swallowing and branding
Liquid-filled softgel	Moderate to high	Moderate to high	Premium positioning and faster-perceived onset
Differentiated clean-label product	Moderate	Moderate	Consumer segmentation and online sales

Revenue exposure depends on retail channel, not only unit volume. A store-brand tablet competes primarily on acquisition cost and fill-rate performance. A branded softgel can support a higher price but requires consumer education and stronger quality controls.

Nighttime analgesics also carry safety-related demand constraints. Sedation, next-day impairment, anticholinergic effects, and NSAID warnings limit the addressable market, particularly among older consumers and patients with contraindications. Product positioning should remain consistent with FDA labeling and should not imply treatment of chronic insomnia.

How strong is the patent estate for Ibuprofen PM?

The patent estate is generally weak for a conventional free-acid ibuprofen and diphenhydramine immediate-release tablet because the active ingredients and basic therapeutic concept are mature.

Patent strength can be materially higher for:

• A novel liquid-filled softgel.
• A specific ibuprofen salt or amorphous dispersion.
• A validated fast-release profile.
• A multiparticulate dosage form.
• A proprietary combination of excipients that solves a defined stability or dissolution problem.
• A specialized manufacturing method with measurable product-performance benefits.

Even in these areas, enforceability depends on claim construction, written description, enablement, prosecution history, and the ability to design around the claims.

Key Takeaways

• Ibuprofen PM is typically a combination of 200 mg ibuprofen and 38 mg diphenhydramine citrate.
• Immediate-release film-coated tablets offer the lowest regulatory and manufacturing risk.
• Ibuprofen’s low solubility makes particle size, disintegrant selection, lubrication, and dissolution control central formulation issues.
• Crospovidone or croscarmellose sodium with microcrystalline cellulose provides a practical starting platform.
• Softgels offer the strongest premium opportunity but carry higher formulation, stability, and manufacturing risk.
• Basic compound patent protection is not the main barrier in this mature OTC category.
• Product-specific formulation, process, packaging, trademark, and trade-dress rights remain relevant.
• Paragraph IV exposure depends on the existence of a qualifying reference application and listed patents.
• Private-label, store-brand, clean-label, and softgel products are the principal commercial opportunities.
• Manufacturing reliability and retail distribution are more important than molecule-level exclusivity.

FAQs

Can ibuprofen and diphenhydramine citrate be combined in one tablet?

Yes. The combination is commercially established, but the formulation must control ibuprofen dissolution, diphenhydramine content uniformity, tablet disintegration, and stability.

Is a sodium ibuprofen PM product equivalent to standard Ibuprofen PM?

Not automatically. Sodium ibuprofen is a different active form with different solubility, formulation behavior, labeling considerations, and potentially a different regulatory pathway.

Is a fast-dissolving Ibuprofen PM tablet patentable?

Potentially, if the product has novel and non-obvious structural or performance characteristics supported by data. A generic claim to faster dissolution without a defensible formulation distinction may face validity and obviousness challenges.

Are softgel excipients better than tablet excipients for Ibuprofen PM?

They are better suited to premium delivery and potentially improved swallowability. They are not inherently better for regulatory simplicity, cost, or stability.

Can Ibuprofen PM be marketed to children under 12 years of age?

Standard nighttime labeling generally does not support use in children under 12. A pediatric product would require an appropriate regulatory, safety, dose, and labeling basis.

References

1. U.S. Food and Drug Administration. (n.d.). 21 C.F.R. Part 343: Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use. Electronic Code of Federal Regulations.

2. U.S. Food and Drug Administration. (n.d.). 21 C.F.R. Part 338: Sleep aid drug products for over-the-counter human use. Electronic Code of Federal Regulations.

3. DailyMed. (n.d.). Ibuprofen PM and diphenhydramine citrate product labeling. National Library of Medicine.

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

5. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions and Paragraph IV certifications. FDA.