List of Excipients in Branded Drug PIRFENIDONE

Generic Drugs Containing PIRFENIDONE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals Inc	pirfenidone	0480-3610	CELLULOSE, MICROCRYSTALLINE
Teva Pharmaceuticals Inc	pirfenidone	0480-3610	CROSCARMELLOSE SODIUM
Teva Pharmaceuticals Inc	pirfenidone	0480-3610	FERRIC OXIDE YELLOW

What are the Most Frequently-Used Excipients in PIRFENIDONE?

# Of NDCs	Excipient
3	ALCOHOL
6	AMMONIA
1	AMMONIUM CATION

Pirfenidone Excipient Strategy and Commercial Opportunities

Last updated: August 20, 2026

Pirfenidone is an off-patent oral antifibrotic with established capsule and tablet products, including Esbriet and generic equivalents. The strongest excipient opportunities are not basic reformulation of the immediate-release product. They are improved gastrointestinal tolerability, reduced pill burden, flexible dosing, stability enhancement, and differentiated delivery for patients with idiopathic pulmonary fibrosis (IPF) or other fibrotic diseases.

The commercial market is exposed to generic price competition, but formulation, device, packaging, and indication-specific strategies can still create defensible positions. Immediate-release tablets and capsules remain the lowest-risk products. Modified-release, orally disintegrating, multiparticulate, and combination approaches offer greater differentiation but carry higher clinical and regulatory risk.

What excipients are used in pirfenidone products?

Commercial pirfenidone products generally use conventional solid oral excipients. The formulation architecture is compatible with direct compression or conventional granulation, film coating, and hard-gelatin capsule filling.

Representative Esbriet excipients

The US Esbriet label identifies the following inactive ingredients for the 267 mg capsules and tablets:

Formulation element	Representative excipients	Functional role
Tablet or capsule core	Microcrystalline cellulose	Diluent, compression aid
Tablet or capsule core	Croscarmellose sodium	Superdisintegrant
Tablet or capsule core	Povidone	Binder
Tablet or capsule core	Colloidal silicon dioxide	Glidant, flow aid
Tablet or capsule core	Magnesium stearate	Lubricant
Film coating	Hypromellose and related coating materials	Film formation and protection
Color system	Titanium dioxide and iron oxides	Identification and appearance
Capsule shell	Gelatin, titanium dioxide, iron oxide	Shell formation and color
Printing	Pharmaceutical ink	Product identification

The precise excipient composition can differ between the capsule, 267 mg tablet, and 801 mg tablet presentations. Generic applicants may use different excipients if the product meets quality, bioequivalence, dissolution, and stability requirements. [1]

The formulation is not dependent on a complex delivery platform. That lowers manufacturing barriers and increases the likelihood of generic substitution.

What formulation problems should an excipient strategy solve?

Pirfenidone excipient selection should address four commercial problems: gastrointestinal intolerance, food-related administration complexity, high daily tablet burden, and long-term adherence.

The labeled titration schedule reaches 801 mg three times daily, or 2,403 mg per day. A patient taking 267 mg tablets may need nine tablets daily after titration. The 801 mg tablet reduces the number of units but creates a larger tablet with higher swallowing and manufacturing requirements. [1]

Commonly reported adverse reactions include nausea, dyspepsia, diarrhea, vomiting, anorexia, fatigue, and weight loss. Esbriet is recommended with food to reduce gastrointestinal adverse reactions. A formulation that improves gastric residence, moderates release, or reduces local intestinal exposure could have commercial value if it preserves systemic exposure. [1]

Priority excipient functions

Product objective	Excipient or technology direction	Commercial value
Reduce nausea and dyspepsia	Hydrophilic matrix, multiparticulate release, lipid or polymeric carrier	Possible adherence benefit
Improve tablet robustness	Coprocessed cellulose, spray-dried mannitol, optimized binder system	Lower breakage and manufacturing cost
Improve swallowing	Smaller multiparticulates, orally dispersible granules, high-load tablet design	Useful for elderly patients
Control release	Hypromellose, ethylcellulose, methacrylate polymers, lipid matrices	Potentially fewer daily doses
Improve powder flow	Colloidal silicon dioxide, silicified microcrystalline cellulose	Higher-speed compression
Manage moisture	Desiccant packaging, moisture-barrier blister, low-hygroscopic excipients	Better stability and global distribution
Improve palatability	Film coating, taste-masking polymer, coated granules	Relevant to pediatric or dysphagia products

Which pirfenidone formulation opportunities are commercially attractive?

Immediate-release 801 mg tablet

The 801 mg tablet is the most practical near-term product. It reduces pill burden and fits the existing dosing regimen without requiring a new pharmacokinetic profile.

A generic or authorized-generic manufacturer can compete through:

• lower manufacturing cost;
• improved tablet hardness and friability;
• smaller tablet dimensions;
• more efficient packaging;
• lower-cost film coating;
• unit-dose adherence packs;
• alternative color and imprint systems;
• hospital and specialty-pharmacy supply reliability.

The principal limitation is weak differentiation. A standard immediate-release tablet is likely to face rapid price erosion once multiple approved suppliers enter.

Modified-release pirfenidone

A twice-daily or once-daily formulation would offer the clearest patient benefit. The product could use hydrophilic matrix polymers, coated multiparticulates, osmotic technology, or lipid-based release control.

The technical target is not merely slower dissolution. The formulation must maintain adequate total exposure while avoiding a high early concentration that may contribute to nausea or other intolerance. It must also address the existing food effect and demonstrate comparable or clinically acceptable exposure across fed and fasted conditions.

A modified-release product would likely require a more complex regulatory pathway than a conventional abbreviated new drug application. If the dosage form is materially different, the sponsor may need a new drug application or a supplemental clinical program rather than relying solely on conventional generic bioequivalence.

Multiparticulate or sprinkle formulation

Multiparticulates can provide several advantages:

• flexible dose adjustment;
• improved swallowing;
• lower risk of dose dumping than a single large matrix tablet;
• potential coating-based release control;
• possible administration through selected enteral feeding systems.

The main excipient choices would include microcrystalline cellulose or sugar spheres as starter cores, polymeric seal coats, functional release coatings, anti-tacking agents, and taste-masking layers.

This format has commercial relevance for patients with dysphagia, advanced age, or impaired tablet handling. It also creates more formulation-specific intellectual property than a conventional tablet.

Orally disintegrating tablet or granule

An orally disintegrating product could improve administration without water. Mannitol, crospovidone, low-substituted hydroxypropyl cellulose, and flavor or taste-masking systems are common development options.

Pirfenidone’s dose burden makes a single-unit orally disintegrating product difficult. A high-strength 801 mg orally disintegrating tablet may be too large or require aggressive compression and taste masking. A lower-strength product may improve administration but increase the number of units.

The strongest use case is an orally dispersible granule or multiparticulate sachet rather than a conventional high-dose orally disintegrating tablet.

How should excipients be selected for pirfenidone stability?

Pirfenidone is a small, orally active molecule with a relatively simple solid-dose manufacturing profile. Stability work should focus on moisture, oxidation, coating compatibility, dissolution drift, and extractables from packaging.

High-priority development studies

1. Moisture sorption: Compare conventional microcrystalline cellulose with silicified grades, mannitol, and low-moisture fillers.
2. Lubrication sensitivity: Control magnesium stearate concentration and blending time because over-lubrication can slow dissolution.
3. Coating protection: Assess whether the film coat changes dissolution after accelerated storage.
4. Packaging interaction: Evaluate high-barrier bottles, alu-alu blisters, and desiccant systems.
5. Scale-up flow: Confirm content uniformity and tablet weight control at commercial compression speed.
6. Dissolution robustness: Test across pH conditions, agitation rates, and post-storage time points.
7. Nitrosamine and elemental impurity controls: Review excipient, ink, coating, and packaging sources under current ICH and FDA expectations.

Excipients should be selected from established compendial and regulatory databases where possible. Novel excipients can create a stronger technical position but may increase regulatory review and supplier qualification costs.

What patents protect pirfenidone formulations and methods of use?

The original US Esbriet exclusivity period has ended. Pirfenidone received FDA approval for IPF in October 2014, and its five-year new chemical entity exclusivity therefore expired in 2019. [1,2]

The remaining competitive position has historically depended on formulation, dosing, method-of-use, and regulatory exclusivity rather than the basic composition of matter.

Patent categories relevant to pirfenidone

Patent category	Typical subject matter	Relevance
Composition of matter	Pirfenidone molecule	No longer a practical US barrier
Basic therapeutic use	Treatment of pulmonary fibrosis	Historically important; expiration limits current protection
Dose and titration	Escalation toward 801 mg three times daily	May support method-of-use positions
Formulation	Modified release, coated particles, improved tolerability	Main area for new commercial IP
Combination therapy	Pirfenidone with another antifibrotic or supportive agent	Potentially valuable but clinically dependent
Manufacturing	Crystallization, impurity control, particle engineering	Can raise supply-chain barriers
Packaging	Moisture control and adherence systems	Usually secondary protection

FDA-approved generic pirfenidone products have reduced the practical value of broad legacy patents. New formulation patents must claim a measurable technical result, such as a defined release profile, reduced peak concentration, improved fed-fast exposure, lower adverse-event rates, or enhanced stability.

A patent covering only a different excipient substitution is usually vulnerable unless the substitution produces an unexpected and reproducible performance benefit.

What is the FDA and Orange Book status of pirfenidone?

Esbriet is FDA-approved for adults with IPF. The reference product is marketed as 267 mg capsules, 267 mg tablets, and 801 mg tablets. The approved regimen begins with dose escalation and reaches 801 mg three times daily. [1]

Pirfenidone has no biosimilar pathway because it is a synthetic small molecule, not a biologic. Generic competition proceeds through the abbreviated new drug application pathway.

The Orange Book remains the key source for current listed patents, exclusivity codes, and therapeutic-equivalence information. The relevant commercial conclusion is that NCE exclusivity is expired and generic competition is established. Any remaining listed patent must be evaluated claim by claim against the proposed dosage form, strength, labeling, and manufacturing process. [2]

Which companies are challenging or competing with Esbriet?

Pirfenidone competition comes from generic manufacturers rather than biosimilar developers. The market includes the reference product from Genentech/Roche and generic products from multiple manufacturers in the US and international markets.

Competitive intensity varies by country because approval status, reimbursement, local patent rules, and tender purchasing differ. In the US, generic entry reduces the value of an undifferentiated immediate-release product. In emerging markets, supply reliability, local registration, price, and government procurement can be more important than formulation differentiation.

The principal branded competitor is nintedanib, marketed as Ofev by Boehringer Ingelheim. The two products compete in IPF but have different pharmacology, safety profiles, dosing, and formulation requirements.

Attribute	Pirfenidone	Nintedanib
Product type	Small-molecule oral antifibrotic	Small-molecule oral antifibrotic
Reference brand	Esbriet	Ofev
Dosing burden	Typically three times daily after titration	Typically twice daily
Key formulation opportunity	Lower burden and improved GI tolerability	Dose flexibility and GI management
Biosimilar exposure	None	None
Generic risk	Established and material	Dependent on applicable patent and regulatory barriers
Main commercial differentiator	Cost, adherence, tolerability	Dosing convenience, indication breadth, clinical positioning

What licensing deals and partnering opportunities exist for pirfenidone?

Pirfenidone’s original commercial history included regional licensing and development arrangements before global commercialization by Roche’s Genentech unit. The current partnering opportunity is more likely to involve differentiated formulations, regional commercialization, or lifecycle management than licensing the basic active ingredient.

Attractive partnering models

• Regional generic licensing: Local registration and tender access in markets where manufacturing or distribution is fragmented.
• Formulation licensing: Rights to a modified-release, multiparticulate, or orally dispersible product.
• Specialty-pharmacy partnerships: Adherence programs, dose-escalation packs, and patient-support services.
• Contract manufacturing: High-volume production of 801 mg tablets or capsules.
• Combination development: Pirfenidone with investigational antifibrotic, anti-inflammatory, or metabolic agents.
• Indication expansion: Development in non-IPF fibrotic diseases, subject to clinical evidence and regulatory approval.

The strongest asset for licensing is a clinically validated formulation. A patent application without human pharmacokinetic or tolerability data is less attractive to an established pharmaceutical partner.

How strong is the pirfenidone formulation patent estate?

The legacy estate is commercially weaker than it was before generic entry because composition-of-matter and early use protections have expired or lost practical blocking effect in major markets.

A new formulation estate can be strong if it includes:

• composition claims covering a defined excipient range;
• dissolution or pharmacokinetic claims;
• claims tied to reduced peak exposure;
• fed-state and fasted-state performance;
• manufacturing-process claims;
• stability claims;
• device or packaging claims;
• clinical claims linked to improved tolerability or adherence.

A formulation patent based solely on a conventional excipient list is likely to have limited exclusionary power. The best strategy is a layered estate combining formulation, process, use, packaging, and device claims.

What generic launch scenarios exist for pirfenidone?

Scenario 1: Low-cost immediate-release entry

This is the most likely and lowest-risk scenario. Multiple manufacturers supply 267 mg and 801 mg products, with price competition concentrated in formularies, specialty pharmacies, and government procurement.

Scenario 2: Branded-generic differentiation

A manufacturer markets a product with adherence packaging, smaller tablets, improved bottle design, or dependable supply. Price remains important, but the product may gain share through payer and pharmacy relationships.

Scenario 3: Modified-release relaunch

A sponsor develops a twice-daily or once-daily formulation. The opportunity is larger, but clinical and regulatory costs rise substantially. The product must demonstrate a meaningful advantage over inexpensive immediate-release generics.

Scenario 4: International formulation expansion

A company targets markets where IPF diagnosis and treatment access are increasing. A stable, low-cost tablet with local manufacturing or regional packaging may produce better returns than a US-focused lifecycle product.

What revenue exposure does pirfenidone create?

Revenue exposure is concentrated in the reference product, generic suppliers, active pharmaceutical ingredient producers, specialty pharmacies, and contract manufacturers.

The reference brand faces three structural pressures:

1. generic substitution;
2. loss of exclusivity;
3. competition from nintedanib.

Generic suppliers face lower margins but can benefit from recurring chronic use, global demand, and relatively straightforward oral-solid manufacturing. Excipient suppliers can capture value through high-volume grades of microcrystalline cellulose, croscarmellose sodium, povidone, colloidal silicon dioxide, magnesium stearate, coating polymers, and moisture-barrier packaging.

The most defensible value is likely to sit in differentiated delivery rather than commodity excipient supply.

What geographic markets offer the best opportunity?

The US is attractive for scale but has intense generic competition and payer pressure. Europe has broad demand but country-specific pricing and reimbursement constraints. Japan, South Korea, China, India, and Latin America offer opportunities tied to local registration, manufacturing, and distribution capability.

A geographic strategy should prioritize:

• countries with increasing IPF diagnosis;
• markets where generic substitution is established;
• regions with limited access to 801 mg presentations;
• countries where local production receives procurement preference;
• markets where capsule or tablet excipients can be sourced economically.

Global registration also requires attention to excipient acceptability, colorant restrictions, gelatin sourcing, nitrosamine controls, and packaging requirements.

Key Takeaways

• Pirfenidone is a synthetic small molecule with no biosimilar pathway.
• Esbriet’s US NCE exclusivity expired in 2019, and generic competition is established.
• Conventional excipient systems use microcrystalline cellulose, croscarmellose sodium, povidone, colloidal silicon dioxide, magnesium stearate, coating polymers, and capsule-shell materials.
• The 801 mg immediate-release tablet is the lowest-risk commercial product but has limited differentiation.
• The strongest formulation opportunity is a modified-release or multiparticulate product that reduces dosing burden or improves gastrointestinal tolerability.
• New IP should combine excipient composition, release profile, pharmacokinetics, manufacturing, packaging, and method-of-use claims.
• Pirfenidone competes commercially with nintedanib, particularly on dosing convenience, tolerability, price, and access.
• Licensing value is highest for clinically validated differentiated formulations, not basic excipient substitutions.
• Generic launch risk is high for undifferentiated immediate-release products and lower for technically differentiated delivery systems.

FAQs about pirfenidone excipients and commercial strategy

Can pirfenidone be formulated as a once-daily tablet?

Yes, but a once-daily product would require controlled-release technology and clinical evidence showing acceptable exposure, tolerability, and efficacy relative to the approved three-times-daily regimen.

Which excipient is most important for pirfenidone tablet performance?

The disintegrant-binder-lubricant balance is critical. Croscarmellose sodium, povidone, microcrystalline cellulose, and magnesium stearate must be optimized together because excessive lubrication or insufficient disintegration can reduce dissolution performance.

Is pirfenidone suitable for an enteric-coated formulation?

It may be technically feasible, but enteric coating would alter the site and timing of release. The formulation would need to preserve exposure and demonstrate a meaningful tolerability or stability advantage.

Can pirfenidone be developed as a pediatric formulation?

A pediatric formulation could use granules, dispersible tablets, or multiparticulates. Taste masking, dose flexibility, excipient safety, and clinical evidence would be central development requirements.

What is the best commercial strategy for a pirfenidone generic?

For immediate entry, the best strategy is a cost-efficient 801 mg tablet with reliable supply, high-quality packaging, and strong specialty-pharmacy distribution. For durable differentiation, a validated modified-release or multiparticulate formulation offers greater value.

References

1. Genentech USA, Inc. (2023). Esbriet (pirfenidone) prescribing information. U.S. Food and Drug Administration.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2014). FDA approves Esbriet to treat idiopathic pulmonary fibrosis.
4. King, T. E., Jr., Bradford, W. Z., Castro-Bernardini, S., Fagan, E. A., Glaspole, I., Glassberg, M. K., Gorina, E., Hopkins, P. M., Kardatzke, D., Lancaster, L., Noble, P. W., Sahn, S. A., Sussman, R., Swigris, J. J., & Valeyre, D. (2014). A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New England Journal of Medicine, 370(22), 2083-2092.
5. European Medicines Agency. (2011). Esbriet: European public assessment report.
6. U.S. Food and Drug Administration. (2024). Inactive ingredient database.